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BMJ AIDS Debate The British Medical Journal
AIDS Debate
2003–2005


Responses to the March 2003 BMJ article
The politics of AIDS in South Africa:
beyond the controversies

by Didier Fassin and Helen Schneider



Mbeki's AIDS Panel still active 28 February 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Mbeki's AIDS Panel still active

Dear Editor,

Didier Fassin and Helen Schneider say that in "April 2002...Mbeki formally distanced himself from the AIDS 'dissidents'". I have read reports in the newspapers making such wishful claims, but none has been confirmed by the South African government, certainly not by the president. I am a member of Thabo Mbeki's AIDS Advisory Panel, which is still in existence. None of us on his AIDS Panel was informed that Mbeki no longer has need of our services. His government continues to call upon us for advice and assistance. What evidence do Fassin and Schneider have that Mbeki formally or otherwise has distanced himself from the AIDS dissidents? Can they cite their sources of this information?

David Rasnick, PhD

AIDS dissident and still a Member of the President's AIDS Advisory Panel

Competing interests:   Member of President Mbeki's AIDS Advisory Panel


The politics of AIDS in South Africa 28 February 2003
David Rasnick,
Chief Science Officer, Boveran, inc.
San Ramon, CA 94583

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Re: The politics of AIDS in South Africa

Dear Editor,

Didier Fassin and Helen Schneider wish to talk about "The politics of AIDS in South Africa". Let's do just that.

Almost daily the newspapers and television tell us that 25 million people have died of AIDS, and there are upwards of 40 million people infected with HIV. However, since the USA reports a cumulative number of only three quarters of a million AIDS cases since 1980, and Europe reports even fewer, that means that over 95% of all those AIDS deaths and HIV infected people must be somewhere else. That somewhere else, according to the newspapers, is Africa, India, and increasingly China.

Because of its international importance, South Africa is the biggest roadblock impeding the expansion of American-dominated AIDS Incorporated throughout the developing world. The battle to determine the future of AIDS Inc. is being waged right now in South Africa.

South African president Thabo Mbeki's government is justifiably suspicious of the rush to get the highly toxic anti-HIV drugs into South African bodies. The South African government is currently conducting trials in 18 centers across the country to determine the safety and efficacy of administering the anti-HIV drug nevirapine to pregnant women and their babies. The trial was to be completed in December 2002 but not enough women have volunteered. However, AIDS Inc. cannot afford to let this trial go to completion for two reasons: 1) the results may show that the drug is neither safe nor efficacious, and 2) the government of South Africa cannot be permitted to set the example of acting independently of AIDS Inc. when it comes to AIDS.

Realizing that South Africa is crucial to its expansion, AIDS Inc. drafted former president Jimmy Carter and billionaire Bill Gates to do battle with Thabo Mbeki in March, 2002. Carter said he and Gates believed South Africa had not made "adequate progress" in preventing new cases of Aids, which were increasing "by leaps and bounds every day".

Jimmy Carter urged President Mbeki to learn the lessons from poorer African countries that have been much more effective in fighting AIDS--which translated means those African countries that have submitted to the hegemony of AIDS Inc.

Former president Mandela joined Carter and the other drugs-into- bodies enthusiasts saying that, "We can't afford to be conducting debates while people are dying. We have to ensure that our people are given the drugs which are going to help them. This is a war."

War, indeed! President Clinton declared AIDS a national security threat to the USA in 2000, right before Mbeki's State visit to the Whitehouse.

On March 10, 2002, Smuts Ngonyama of the African National Congress (ANC) lashed out at Jimmy Carter's attempt to pressure Mbeki's government.

"We are also surprised at the comments made by the [Carter] delegation about anti-retrovirals drugs in general and Nevirapine in particular.

"We do not understand why US citizens urge this drug upon us when the health authorities in their own country do not allow its use for mother-to-child transmission [of HIV]. One of the reasons for this is that these health authorities say that there is insufficient data about issues of the safety of the drug.

"We find it alarming that President Carter is willing to treat our people as guinea pigs, in the interest of the pharmaceutical companies, which he would not do in his own country.

"The comments he and others made after meeting with President Mbeki indicate the true purpose of his visit to our country, which was arranged without the knowledge of the government.

"Once more, we would like to assure President Carter that our government is firmly committed to meet the health challenges facing our people, including AIDS, STD's, TB, cholera, malaria and others.

"For this, we do not need the interference and contemptuous attitude of President Carter or anybody else. As South Africans, we have the possibility to find solutions to our problems, as the people of the US have.

"We are not arrogant to presume that we know what the US should do to respond to its many domestic challenges. Nobody from elsewhere in the world should presume they have a superior right to tell us what to do with our own challenges."

If AIDS Inc. can pry open the drugs-into-bodies floodgates in South Africa, then billions of dollars will pour through Africa, India, and China on their way to the bank accounts of American and other drug companies. The giant corporations will get richer beyond measure whether or not giving nevirapine to women and children (or anybody else for that matter) is a good idea as Costa Gazi, Zackie Achmat, Jimmy Carter, Bill Gates, and Nelson Mandela claim, or insane and criminal as the black box warning label of nevirapine makes clear.

http://www.viramune.com/

Boehringer Ingelheim Pharmaceuticals, Inc. 2001,

Viramune (nevirapine)

WARNING

"Severe, life-threatening, and in some cases fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis and hepatic failure, has been reported in patients treated with VIRAMUNE . In some cases, patients presented with non- specific prodromal signs or symptoms of hepatitis and progressed to hepatic failure. Some events occurred after short-term exposure to VIRAMUNE. Patients with signs or symptoms of hepatitis must seek medical evaluation immediately and should be advised to discontinue VIRAMUNE. (See WARNINGS)

"Severe, life-threatening skin reactions, including fatal cases, have occurred in patients treated with VIRAMUNE. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions must discontinue VIRAMUNE as soon as possible. (See WARNINGS)

"The first 12 weeks of therapy with VIRAMUNE are a critical period during which it is essential that patients be monitored intensively to detect potentially life-threatening hepatotoxicity or skin reactions. VIRAMUNE should not be restarted following severe hepatic, skin or hypersensitivity reactions. In addition, the 14-day lead-in period with VIRAMUNE 200 mg daily dosing must be strictly followed. (See WARNINGS)"

David Rasnick

Competing interests:   Member of Mbeki's AIDS Advisory Panel


The priority should be to preserve humanity 1 March 2003
Richard G Fiddian-Green,
None
None

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Re: The priority should be to preserve humanity

The call for the "discussion of AIDS in South Africa .... to move beyond a simplistic "for or against" stance on President Mbeki's denial of a connection between HIV and AIDS" is appropriate for the conflict misses the primary issues(1). As the WHO data, reviewed in yesterday's Financial Times, show population growth is out of control in Africa and elsewhere unless the AIDS story is real. Herein lies the rub for the AIDS story is simply not credible (2,3). Concealing the truth or manipulating the facts to achieve some hidden agenda is suicidal if, as I have argued, disproportionate population explosion and its accompanying environmental destruction threatens not only peace but also the survival of man on earth

Our first priority should be to define the threats to the human race and the actions that need to be taken, if necesary, to deal with them in a timely manner. All other agendas are of lessr importance. The problem is that there may be an irresistable temptation to fiddle the figures to secure the less important and potentially divisive agendas. Perhaps, therefore, we should begin with a full disclosure of all hidden agendas and the means that are being used to pursue them in the spirit of the South African Truth and Reconciliation Commission. We cannot, however, afford to delay resolution by working at the pace customary in the UN.

1. The politics of AIDS in South Africa: beyond the controversies Didier Fassin and Helen Schneider BMJ 2003; 326: 495-497

2. HIV/AIDS: the biggest error? Richard G Fiddian-Green bmj.com/cgi/eletters/320/7237/0#7270, 4 Apr 2000

3. Let us call a spade a spade Richard G Fiddian-Green bmj.com/cgi/eletters/326/7381/126/e#28968, 20 Jan 2003

Competing interests:   None declared


Political Mobilisation against HIV in South Africa 1 March 2003
Jack P Lewis,
Senior Lecturer at the Institute for Film and New Media at the University of Cape Town
IFNM, Betram Place, Hiddingh Hall Campus, UCT, Cape Town, South Africa

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Re: Political Mobilisation against HIV in South Africa

In response to Fassin and Schneider - I would like to submit the this report by Ralph Berold on the protest march supported by 20 000 people organised by the Treatment Action Campaign (TAC) at the opennig of Parrliament on the 14th February 2003. The article beautifully captures the nature of the TAC, a movement which is seen by many as a critical force for breaking the logjam in AIDS policy.

The TAC has contributed mightily to mobilizing domestic and international opinion to create access to life saving medicine. There can be no doubt highy active anti-retorival treatment (HAART)makes a huge difference to the ability of particularly men to be open about their HIV status. This opponness is the critical ingredient for encouraging safer sexual practice and a lower rate of new infections. Proper treatment of opportunistic infections **and** HAART **combined** with strong social mobilisation as referenced by the politics of the TAC, has shown that it can provide the crucial missing link in effective HIV prevention. This is what we mean when we say that treatment and prevention "are two sides of the same coin". This "combination therapy" - the combination of effective clinical management and a geneuine commitment to the broader social needs of poor people - creates an environment in which men who otherwise might not care about the possibiilty that they may be causing new HIV infections, to improve their health status, take responsibility for their actions and do everything in their power to ensure they do not infect others. This is the experience of thousands of people who have become active in the TAC. The introduction of widespread availability of HAART through the public health system and continued social mobilisation is the best prescription we have to bring down the rate of new infections and reduce mortality in the HIV epidemic in South Africa.

Jack Lewis
Institute of Film and New Media
University of Cape Town
jlewis@hiddingh.uct.ac.za

ARTICLE OF RALPH BEROLD FOLLOWS

Get up stand up!

I wasn't sure whether I would go to the march for HIV treatment,organised by the Treatment Action Campaign (TAC) at the opening of Parliament. The thought of the 36 hour train journey, only 12 hours in Cape Town and then another 36 hours back, had something to do with it.

But I realised last week that this was an important journey for me. I had become passionate about the issues. I scan the papers and email for news on changes in HIV/AIDS policy. It is time for government to take care of some of its 4 to 5 million citizens who are living with HIV. This must be shown not in empty promises and policies, but in practical terms, through a better public health system and universal access to life saving medicines. These changes have been proposed in a document which has been under discussion for the last three months at NEDLAC.

"Don't go there and insult our President" one comrade said. I explained that TAC was not trying to insult or take over our government. We are open about our motives - We want government and organised business to sign the framework agreement that have been negotiating. Let us stop fighting and move forward on this issue. Together, as South Africans we are facing one big challenge.

We left at 9pm on Wednesday night from Park Station. About 600 activists from Gauteng, Mpumalanga, KZN and Limpopo province boarded the train and began singing. The songs did not stop for three days. On Thursday we ran workshops in the dining car. We looked after people that were on TB treatment. Logistics such as catering for 600 through one narrow passage was a nightmare. But people were patient and efficient and there was an air of respect, a partnership amongst strangers.

I met a policeman who had disclosed his status and was an active HIV role model and educator. I met counsellors, toyi-toyi boys, nurses, old people, students, researchers and journalists on the train - each with a common purpose. We stopped at Beaufort West in the afternoon. Staggered into an air conditioned Wimpy for a coke and to our delight and surprise we found an oasis in this dusty town - a deep blue public swimming pool. We swam in our clothes.

Friday morning we hit Cape Town station. In the light rain we gathered and were issued our "HIV positive" T-shirts. 600 people walked to St George's cathedral distributing pamphlets to people on the streets. At the former church of Archbishop Desmond Tutu, we ate breakfast and met up with our Cape Town compatriots. Six of us split the scene, with some hours to kill before the march was scheduled to begin. We roamed the Company Gardens, past the back of Parliament, Tuynhuis - the official residence of the President, past the National Gallery. We were allowed into the National Museum for free where we saw the massive bones of whales and million year old rocks and crystals.

The six of us then made our way to the start of the march down Adderly Street, where the presidential guard stood at attention, dressed in full colours. Clad in our "loud" T-shirts we passed them handing out flyers to the growing crowd. When we reached the TAC crowd, the president and his armoured BMWs drove past. TAC activists lining the streets. Our marshals, identified in red T-shirts kept the crowd from pushing forward to meet the President's motorcade. Anxious police officers.

The rally started at about 12:30. Amampondo hammered out some beautiful melodic rhythms on their marimbas. A flatbed truck served as a stage for speakers and a sound system. Patricia de Lille was one of the first to speak. She said that today she had left Parliament to march with TAC. She reported that the President, in his "state of the nation speech", talked about the US and Iraq for 20 minutes and just mentioned HIV/AIDS in passing, not even by name. Archbishop Njongonkulu Ndungane did not mince his words - "they say that we do not have money for antiretroviral drugs, yet we can pay R60 billion rand for arms!". Where are our priorities?

Then about 20 000 people stood up and arranged themselves in legions -groups in which they would march up Adderley Street. First the people living openly with HIV and AIDS. Then the religious and political leaders. Then the unions. Gays and lesbians. Students. NGOs and community based organisations. Each activist knew why they were there. "HIV treatment for all". We sang, shouted, toyi-toyed, clapped hands and moved forward. Shop workers came to their doors to give their support. Pedestrians were swept into the tide of our wave. I looked up the street and as far as I could see were thousands of people. The power of our bodies and our determination.

In front of Parliament we stopped. A mass meeting at the gates of power. TAC chairperson Zackie Achmat told us how the great rivers of Africa were not big enough to hold our tears, our grief of loved ones lost or dying. He said that we needed to move into a new era, where the people of this country will be cared for, and we will all be afforded the dignity and rights that we deserve. Comrade Willie Madisha, president of COSATU, reminded us that we had spent six months negotiating this deal. Representatives from government, business, labour and the community had come to a consensus and had drafted a framework agreement for a treatment plan. This was meant to be signed on the 1st December. It has not yet been signed. The President and minister continue to deny that it is worth anything.

Each day over 1000 people die of AIDS-related illnesses. Each day without good doctors, nurses and medicines, means another 1000 die. That is 7000 a week, and over 28 000 a month, 300 000 per year, until more than 5 million South Africans will die. Mr President - we plea you, we ask you, we demand of you, to declare a national emergency and to agree to a national HIV/AIDS treatment plan!

By Ralph Berold, February 2003
beroldr@hr.wits.ac.za

Competing interests:   None declared


Killing the geese that lay the golden eggs 2 March 2003
Richard G Fiddian-Green,
None
None

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Re: Killing the geese that lay the golden eggs

Parties within the medical profession and the environmental movements are, through ignorance, guilty of being party to killing the geese that lay the golden eggs (1,2,3).

The primary objective for the medical profession should be to do anything legitimate within their power to maximize longevity and especially disability-adjusted longevity for their patients and their descendents. As we cannot always have what we want and have to bow to economic realities we have, therefore, to choose what is the most cost- effective. That means we have first to be able to define what is meant by effective. Agreement upon this definition appeared to have been reached but only very recently. We need to measure the effectiveness of outcomes in terms of life-years and disability-adjusted life-years saved.

Whatever the cause or causes of premature death and disability the sooner one is able intervene effectively the more cost-effective the intervention is likely to be It should be appreciated that unless a given treatment has been shown, by appropriate statistical means when the therapeutic benefit is not obvious, to be effective it can never be considered cost-effective. This eliminates an embarrisingly large number of therapeutic interventions especially in medical as opposed to invasive practices. Once a treatment is shown to be effective its cost-effectiveness can be determined. For both medical treatments and measures devised to address environmental causes this may be best expressed in terms of dollars spent per incremental life-year or disability-adjusted life-year saved (4,5,6). Only when these steps have been taken is it possible for us to make rational decisions.

From the outcry they provoke it is clear that rational choices do not necessarily equate with popular choices even amongst the medical profession and basic scientists whom one would have assumed were most capable of making rational judgements (1,3,7,8,9). Part of the problem may ralate to a lack of appreciation for what it is that really causes diseases that cause disabilities and death (10). Part of the problem may be the failure to appreciate that whilst many drugs and environmental pollutants may clearly be harmful exposure to low doses may often be beneficial potentially even in the case of the environmental pollutants(11,12). Part of the problem may be the unreliability of much of the data that have been gathered even by WHO (13). Hidden and highly provocative political agendas may account in part for inaccuracies in the data.

The therapeutic activity of plants or drugs reside in descrete chemicals within them. Furthermore the potency and safety of different products differs widely even when manufacturing controls insure uniformity in the composition of the products. Given this scenario who in their right minds would want to be given a drug manufactured in some third world sweat shop or herb even if genetic engineering insured that it concealed pharmaceutical products with established efficacy? There is a real danger of political forces supported by covert activities undermining the established free market practices of established and highly credible pharmaceutical companies. The attacks against the pricing of AIDS medications in lesser developed countries is one manifestation of these political forces.

The attacks against intellectual property rights is another manifestation of these contraversial and possibly hidden political initiatives. Having worked on both sides of the fence and in both developed and lesser developed countries I have little doubt that free market practices, with some improvements, are by far the best means of keepingall patients supplied with the most effective and theerefopre cost- effective treatments even in lesser developed countries (14,15,16,17). The reality is, as President Mbeki appreciates, that the determinants of cost -effectiveness and hence the ranking of cost-effective interventions be they public health, medical or surgical differ greatly between developed and lesser developed countries.

1. Drug companies face pressure on profits Deborah Josefson BMJ 2002; 324: 65.

2. Thought control The scourge of the greens is accused of dishonesty (From The Economist print edition) Jan 11th 2003

3. Howls from greens The appointment of an eco-sceptic may mark a big change in policy (From The Economist print edition) Mar 2nd 2002

4. Fiddian-Green RG. Tonometry: part 2 clinical use and cost implications. Intensive Care World. 1992 Sep;9(3):130-5. Review.

5. The truth about the environment (From The Economist print edition) Aug 4th 2001

6. Doomsday postponed (From The Economist print edition) Sep 8th 2001

7. Defending science (From The Economist print edition) Feb 2nd 2002

8. Never the twain shall meet (From The Economist print edition) Feb 2nd 2002

9. The litany and the heretic (From The Economist print edition) Feb 2nd 2002

10. Determining the cause of death Richard G Fiddian-Green bmj.com/cgi/eletters/324/7328/41#29384, 3 Feb 2003

11. Dual Effect of energy deficit on hippocampal neurogenesis Richard G Fiddian-Green bmj.com/cgi/eletters/325/7370/934#26556, 28 Oct 2002

12. D'Arcangelo D, Facchiano F, Barlucchi LM, Melillo G, Illi B, Testolin L, Gaetano C, Capogrossi MC. Acidosis inhibits endothelial cell apoptosis and function and induces basic fibroblast growth factor and vascular endothelial growth factor expression. Circ Res. 2000 Feb 18;86(3):312-8.

13. Should WHO confine its activities to monitoring?? Richard G Fiddian- Green bmj.com/cgi/eletters/325/7375/1294#27726, 10 Dec 2002

14. Has the FDA served its function? Richard G Fiddian-Green bmj.com/cgi/eletters/325/7364/592#25700, 20 Sep 2002

15. Patents and their commercial value are essential Richard G Fiddian-Green bmj.com/cgi/eletters/325/7364/562/a#25646, 19 Sep 2002

16. The need to protect intellectual property rights Richard G Fiddian-Green bmj.com/cgi/eletters/325/7363/519#25347, 9 Sep 2002

17. Preparing for the coming healthcare revolution Richard G Fiddian-Green bmj.com/cgi/eletters/325/7375/1290#27463, 29 Nov 2002

Competing interests:   None declared


The reality of AIDS in South Africa 2 March 2003
Kate A Herbert,
none
sw11 1sy,
Didier Fassin, Helen Schneider

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Re: The reality of AIDS in South Africa

Dear Editor

I trust the authors of this informative and interesting article are chuckling to themselves at the response from David Rasnick. The culture of 'suspician and denial' has been evidenced brilliantly.

I welcome the call to move away from the politics of treatment. AIDS is a national emergency in South Africa - an emergency many are still hoping to ignore. Treatment is one option but long term, support at a grass-roots level is essential to prevent the breakdown of the fabric of society.

The authors neglect to mention one staggering statistic: by the end of 2005, it is predicted that there will be 1.5 million children in South Africa orphaned by HIV/AIDS. Children left to struggle on their own. Children who will stop attending school. Children who will one day be disillusion, uneducated adults. It is essential that this aspect of the AIDS pandemic is not ignored.

I spend a lot of my spare time working for Starfish Charity, which is working to provide education, food and accomodation to AIDS orphans in South Africa. I'm a typical white South African living in the UK - and have been living away from South Africa for over a decade. But this has struck a deep chord - and, I fully agree with the authors' conclusion that HIV/AIDS has mobilised both activists and lay people. This issue is not going to go away, no matter how long we argue about treatment or politics. The time to act is now - and it need not be a dramatic gesture. £10 a year pays a child's school fees in rural areas. There is no longer an excuse not to get involved.

Kate Herbert
Starfish Charity
www.starfishcharity.org

Competing interests:   None declared


The invisible epidemic and the AZT intoxication 2 March 2003
Claus Kõhnlein,
M:D:internal Med.
Germany, 24103 Kiel, Kõnigsweg 14

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Re: The invisible epidemic and the AZT intoxication

Thabo Mbeki had probably a similiar approach when doubting the AIDS- epidemic in his country like me. The epidemic is clinically indeed invisible, because none of the 28 AIDS- defining conditions are new. The "epidemic" only becomes visible if you introduce HIV-Tests in a country. So it is nothing more than a "testepidemic". If you rule out the HIV-tests the "Testepidemic " would disappear and you would see again people suffering from tuberculosis, malaria and lepra and the many more infectious diseases which are still common in the third world.

This burden of diseases is related to poverty. We had these problems of poverty after the world wars in our country. It is textbookknowledge that starvation is the cause of pneumocystis pneumonia(Harrisons,Principles of Internal Medicine)It is also well established that immunosuppressive drugs cause PCP. Unfortunately we chose an immunosuppressive drug, namely AZT as a treatment for an AIDS. The journal Science headlined:"Bone marrow suppression hampers AZT use in AIDS victims".

But what does that mean? It means that treatment of the disease itself gives rise for the bleak prognosis for the disease. This is dokumented in the"Darby Study" that was published in Nature in 1995. Darby showed that the mortality of HIV- pos. hemophiliacs rose tremendously after the widespread introduction of AZT in 1987, but related the rise in mortality to HIV and not AZT- thats the controversy!

This controversy could be easily resolved through a simple animal model: feed the HIV infected chimps who are still healthy with 1500 mg of AZT- the dosis the HIV-pos. hemophiliacs had to swallow and look what happens. I would predict AIDS-defining conditions like wasting and loss of CD4 cells within one or two years.

Competing interests:   None declared


Political nonsense 3 March 2003
Richard L. Newell,
Ship's Doctor
In the Caribbean

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Re: Political nonsense

Sir

I would not dream of depriving Fassin and Schneider of their right to receive funding from a French agency to pursue research into the politics of HIV/AIDS, but surely they should do better than this.

They ignore the fact that HIV by and large spread from north to south over the last 20 years, and that the colonial masters had left 20 years before that. Blaming colonialism for the ills of Africa has always been the habit of the chattering classes: nobody can tell what would have happened to the continent's people had the white man not arrived. Furthermore, most of South Africa's mass removals took place before HIV was invented! Also to talk of economic inequalities implies that HIV will attack the poor more aggressively if there are rich people around - as if the rich were somehow responsible for it. But rich black Africans get HIV too; indeed the worst affected communities tend to be those who are employed in the formal sector, i.e. the relatively rich.

The only responses that have any meaning and do not pursue a set agenda come from the South Africans Lewis and Herbert (although it is interesting to see that Herbert recruited the article's authors as co- authors of her letter!). Not so much as a hint of anything that could usefully be done to help the epidemic in South Africa emerges from the article, which is nothing more than another thumping of the old guilt- ridden white man's drum.

Let all of us South Africans try to care for our orphans and sick adults, and let us be energetic in educating the people about risky behaviour. To look for a quick fix to the problems of our country is neither realistic nor helpful. And yes, it is indeed one of the great ironies that HIV has struck its blow just when things were looking up for the African population, but that must not deflect us down politically and therapeutically sterile paths.

Competing interests:   Established and ran an HIV clinic in KZN in South Africa, 1990-91


AIDS in South Africa:The Third Dimension 3 March 2003
Harold D. Foster,
Professor,University of Victoria,Victoria,B.C.,Canada
Departnent of Geography,University of Victoria,P O Box 3050,Victoria,B. C.,Canada.V8W 3P5

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Re: AIDS in South Africa:The Third Dimension

The saddest aspect of the controversy between Dr Peter Duesberg and his supporters and those who insist that HIV alone causes AIDS is that it is so easy to show that both sides of the debate are in error.In 1983,Cuba started to test its population for HIV.Since 1986,all those found positive have been quarantined.Some will view this as a major assault on personal freedom, but it has been an exceptionally effective strategy in preventing the spread of AIDS.AIDS is now roughly twelve times as common in neighbouring Jamaica as in Cuba.Indeed,Cuba has some of the lowest prevalence rates for HIV-1 infection and AIDS on the planet.If,as Duesberg and supporters claim,HIV-1 plays no role in AIDS,why is this the case?

Conversely,after twenty years of multibillion dollar scientific research, supporters of the "HIV alone causes AIDS" hypothesis have provided us with a "treatment cocktail" which relies strongly on AZT,a highly carcinogenic drug, and a vaccine that does not work.As a result global HIV-positive rates continue to increase exponentionally,on target for Hasteltine's prediction of one billion infections by 2015.

In 1990, Dr Luc Montagnier,(who had headed the team that first discovered HIV),published a short paper that showed beyond doubt that HIV alone could not cause AIDS.Montagnier demonstrated that although cultured cells infected with HIV died rapidly,if given the antibiotic tetracycline,they flourished.Since antibiotics do not kill viruses,Montagnier concluded that HIV must require at least one co-factor to cause AIDS.He has been looking for this cofactor ever since.

HIV-1 is a virus that encodes for glutathione peroxidase,part of a group that includes the Hepatitis B and C viruses and the Coxsackie B virus.Field trials with all the other members of this group have shown that adding selenium to diet greatly reduces infection rates.The geographical diffusion of HIV/AIDS, in both Africa and the USA,clearly shows that HIV has major problems infecting those who are not selenium deficient.Anything that causes a selenium deficiency,(from low soil levels through acid rain to infection by other pathogens that encode for a selenoenzyme)will make a population more prone to HIV-1 infection. Adding selenium to diet in Southern Africa and elsewhere would greatly slow the diffusion of HIV-1.Anyone needing more information can download a free copy of "What really causes AIDS" at www.hdfoster.com.

Competing interests:   I have a U.S. patent pending on a nutritional treatment for the reversal of AIDS and have published a book "What really causes AIDS" on the topic.


Priority of Health Education. 3 March 2003
Gabor A. Balint,
professor of clinical pharmacology
Univ.Szeged Med.School.H-6701 Szeged,GPOBox 427. Hungary,
New Clinics,(Dept.of Psychiatry)Lab.Cli.Pharm/

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Re: Priority of Health Education.

Dear Editor,

Drs. Fassin & Schneider state in their article (BMJ.326;495, 2003,)that previous social segregation (apartheid) between Caucasians and Africans in South Africa is translated nowadays as a cause of the different HIV sero- prevalence between the mentioned groups.I am definitely NOT a racist - I have spent more than 6 years in Africa as an expat - BUT their tenet seems to be (from medical point of view) definitely faulty. According to my humble opinion education and social traditions, etc. (e.g. extramarital sex)have a far greater role in this very unfortunate fact.

Therefore our duty is clear- vigorous health education. (See the result in Uganda, please!) Racism is a political and ideological "principle", nothing to do with it in the public health.(But of course we cannot approve it!)

Sincerely yours, G.A.B.

Competing interests:   None declared


HIV in Southern Africa: social and political factors are very relevant, but so is the virus itself! 3 March 2003
Jim Bond,
Specialist Registrar in Public Health Medicine
Dept. of Public Health Sciences, University of Edinburgh, Medical School, Teviot Place, EH8 9AG

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Re: HIV in Southern Africa: social and political factors are very relevant, but so is the virus itself!

I would like to add another critical comment on Fassin & Schneider's otherwise excellent article this week:

As a native Zambian, with first hand clinical experience of AIDS in Southern Africa since 1986 (and in South Africa itself since 1992), I find much to agree with in their analysis of the political and social causes of the HIV epidemic in the RSA. However, what they fail entirely to mention is the role of biological factors, e.g. the nature of HIV-1C, the virus that predominates in this region. In this way, they may have fallen into the same trap as Mr Mbeki...

Yes, undeniably, inequality, mobility and violence have fuelled the flames of HIV transmission there, as throughout the world. South African society does indeed have all three factors in abundance. However, it is not unique, as the authors seem to imply. These pressures affect people all over the world, yet no other region has been quite as badly affected as Southern Africa. So what can we learn from the RSA experience?

Firstly, there are two HIV epidemics in South Africa: The first, among predominantly gay, white men started in the early 1980's and was with the same HIV-1B virus that paved the way in North America, Western Europe and Australasia. It was not until 1987 that the first case of AIDS was diagnosed in a black person there, despite all the inequality, mobility and violence associated with this group. However, within a decade, South Africa had more people with HIV than any other country in the world. Why such a delay and why the sharp rise thereafter? Perhaps the answer lies with the second HIV epidemic, that of HIV-1C, which found its niche among predominantly heterosexual, black Africans...

HIV-1C spread initially from its source of origin to the west of Lake Victoria, both north to Ethiopia and south through Malawi to the countries of the south. (A & D spread east and west.) Although its prevalence was small in 1990, compared with the others, HIV-1C has since shot up exponentially, colonising the Caribbean, India, China and is now the UK. In Africa, it is now moving back up the way into Tanzania (where is has been shown to be 6.7x as transmissible perinatally as HIV-1D), and having a ball in DR Congo, where the Zimbabwean army have no doubt played a part in its spread. Approximately two-thirds of all new infections world- wide are now thought to be HIV-1C. So why is it so successful?

HIV-1C appears to have been selected for vaginal transmission (either sexually or vertically), rather than via rectal or injection routes, like HIV-1B. By at least five different mechanisms it is more aggressive: It specifically targets Langerhans cells in vaginal and penile epithelium; it has a simplified co-receptor mechanism for entering T-cells (i.e. requiring one molecular handshake, instead of two); when inside, it is more readily activated by elevated cytokines such as TNF-alpha, (produced e.g. in response to other STI's and malaria); it produces higher viral loads, so it is more infective; and it mutates and forms recombinants more easily than other HIV-1 viruses. Even its transmission across the placenta is higher (mechanism unknown), so more babies are born infected, with or without peripartum nevirapine prophylaxis...

HIV-1C is probably more aggressive by design - it had to be to survive in the relatively low contact rate niche for which it evolved. Only once it reaches a critical level in the general population is it able to take off, hence the late start in South Africa, Botswana, Namibia etc. Perhaps this is the main reason for the scale of the epidemic in the south!

Ethiopia, was for many years the second highest epicentre for HIV and yet this is not a country with a classical, urban migration pattern. On the other hand, Nigeria, a magnet for migrant workers throughout West Africa, and which therefore one might think should have an epidemic of similar scale to to RSA, has been more fortunate.

Madagascar, which has a good deal of internal migration and inequality-related sexual risk going on - evidenced by its very high rates of other STI's (e.g. syphilis 36%), teenage pregnancy and Western sex tourism, has a very low HIV rate - officially 0.15% in 1999. Even if this was a ten-fold underestimate, it was still 100 times lower than KwaZulu-Natal, just across the water! Yes, there is certainly less sexual violence in Madagascar and almost universal male circumcision, but is that enough to explain the difference...?

I can see why Thabo Mbeki, in a country with two HIV epidemics, one small affecting mainly rich whites and one huge, affecting often poor blacks, would think first of possible confounders such as poverty. His background is in economics, not epidemiology.

He was perhaps unwise to question the links so publicly, so soon into his presidency. It has certainly cost him and the ANC dearly. I would even go so far as to say his reluctance to grasp the nettle of AIDS and to embrace HAART has also undoubtedly contributed to several thousands of people unnecessarily suffering and dying.

However, he is also human and we all make mistakes. There are millions of people who deny the reality of HIV/AIDS daily, either by taking risks with their own lives, or ignoring the plight of neighbours and family already affected. ...perhaps because it's too big or too awful, or they feel so powerless to do anything about it.

However, I believe the Western media has also played a role in this catastrophe. Since the Durban AIDS Conference in 2000, there has not been an HIV event, when some high-minded reporter does not thrust an aggressive microphone at Thabo Mbeki with a reminder of the subject. I myself was once invited onto a radio station on the occasion of the president visiting Scotland to unveil a plaque in honour of his father, Govan Mbeki, an often overlooked hero in the struggle against apartheid. All the interviewer wanted from me was to dig the dirt on Thabo Mbeki and his dissenter stance. No wonder he now instinctly switches off at the sound of the word, 'Aids'!

Perhaps this is not the most contructive way to engage with someone we need to play a pivotal role in leading the region through the current crisis...

PS I haven't used the terms 'subtype' or 'clade', although the former is still the accepted term in the HIV world. HIV-1 subtypes, such as B and C, have remained recognisably stable for over 25 years now, despite their huge turnover and mutation rates. They each have their own specific characters in terms of usual mode of transmission, infectivity and rate of disease progression, at both the individual as well as the population levels. They can, and probably most usefully should, therefore be taxonomically regarded as distinct viruses.

Perhaps if this were more widely recognised, it might help to dispel some of the myths and factoids about African sexuality and social behaviour?

[PPS References available by request]

Competing interests:   None declared


Action not Politics 7 March 2003
Anne Savage,
retired
NA

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Re: Action not Politics

Didier Fasson and colleagues are wrong. Their article will do nothing to bridge any gap, it will just be yet more evidence of the 'North'using the 'South' for useless research. To answer a few of the points:

Many people in the world, predominantly in Muslim countries, are desperately poor but do not have the same incidence of HIV. Health information has been available for years. In 1992 I was in the University of the Transkei at Umtata and the walls were covered with posters statiung 'AIDS is coming. Take precautions,' and giving details. The students took no notice.

Less concern about health and the future is partly a result of the belief system, whereby the spirit not only continues to exist after bodily death but also has an influence on the behaviour of those still alive. Concern about health is difficult to sustain in the face of indifference from the 'North'. Many Africans know that most of their illnesses can be easily cured. They turn up at hospitals in their hundreds only to find the doctor has left or the drugs run out.If even a fraction of the money spent on 'research'was used to fund essentials such as analgesics and first-line antibiotics we, in the 'North' might be able to help stem the time. Why not focus on the'social determinants' contributing to the rise of HIV in our own country, which has all the advantages of wealth, education and treatment?

Competing interests:   None declared


ART and Political Will 12 March 2003
Louis-Jacques van Bogaert,
postdoctoral fellow Centre for Applied Ethics, University Stellenbosch, South Africa
Postnet suite 7 Private Bag x8689, Groblersdal 0470 South Africa

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Re: ART and Political Will

Editor- There is no single, much less simple, explanation or justification of a complex problem. Fassin & Schneider [1] invite the reader "to move beyond a simplistic view" on the South African HIV/AIDS predicament. I an afraid that they only manage to keep the vicious circle of "apartheid bashing" alive and well. To keep blaming everything that is or goes wrong to the legacy of apartheid does not help progress. Worse even, I should argue, their paper might mislead the ill-informed but benevolent reader who might believe that, at lomg last, the government has decided to make anti-retrovirals (ARV) available in the public health services that cater for more than 70 percent of the population (politicians have access to ART through their private health insurances).

A single example, but a telling one, will make this apparent. In this same issue of the journal, the Editor's Choice, AIDS in Africa, states:"In the past year, South Africa has made nevirapine available for pregnant women infected with AIDS"[2]. The reality, however,is that only half of the Provincial Governments, some before and others after the July 2002 Constitutional Court judgement, have started the implementation of the prevention of mother to child transmission (PMTC) of HIV. The other Provinces are in contempt of court by stalling the roll out. One of them is currently on trial for violation of human rights in this regard (case no 35272/02 High Court of South Africa, Transvaal Provincial Division).

I wish to claim loud and clear that I have no inclination whatsoever in favour of apartheid. During the transition from apartheid to democracy (from the liberation of Nelson Mandela in 1990 till the first democratic elections of 1994) I have been victimised and harmed for allegedly being a "communist" (the arch enemies of apartheid). Under the new dispensation I got labelled "activist" (as bad) for advocating women's reproductive health and rights (with the support of the Treatment Action Campaign).During all these years, as referred to by the authors, an annual "anonymous survey of antenatal women" has been run showing a 0.7 percent prevalence in 1990 and a 36.2 percent in some Provinces in 2000. This survey was initiated during apartheid (who knows for what purpose) and taken over by the post-apartheid dispensation. What could be the use and the ethics if the survey did not lead to steps to prevent or limit the onslaught? I wish not deny thye many factors that have contributed to the epidemic. However, one should present the facts undisguised. I fail to understand why or rather how "adults with a single lifetime sexual partner face an extraordinary high prevalence of HIV". What I know about a Carleton survey sponsored by the Population Council is that it was initially thought that the local spread of HIV was a matter of sex- workers/mineworkers. To their surprise, it showed that it was much more intricate (but promiscuity, wherever, is taboo and politically incorrect).

Colonialism and racism/apartheid are an unfortunate and ugly face of humankind. They have been with us from times immemorial. No continent has escaped. Africans themselves have invaded and conquered neighbouring countries. Colonialism begot anticolonialism and later neocolonialism. Apartheid begot antiapartheid. Let's beware of neoapartheid/reverse apartheid. To deny or even to stall the PMTC on the grounds that is "poisons" women with Western medicines is nothing else but racism/reverse apartheid. Unfortunately, it has the perverse effetc of victimising the very same people politicians claim to protect.

[1] Fassin D, Schneider H. The politics of AIDS in South AFrica: beyond the controversies. BMJ 2003;326:495-97.

[2] Editor's choice. AIDS in Africa. BMJ 2003; 326.

Louis-Jacques van Bogaert
Postdoctoral fellow, Centre for APplied Ethics, University of Stellenbosch
E-mail: ljfvanbo@lantic.net

Competing interests:   None declared


HIV in South Africa 13 March 2003
Eleni Papadopulos-Eleopulos,
Medical Physicist
Perth Western Australia 6009,
Valendar F. Turner, John M Papadimitriou, Barry A. P. Page, Sam Mhlongo, Helman Alfonso, David Causer, Christian Fiala and Anthony Brink

Send response to journal:
Re: HIV in South Africa

HIV in South Africa

 

We agree with Fassin and Schneider (Education and Debate, 1 March) that "contrary points of view should be understood rather than discredited".  Consider their statement "…denial — a common response among people facing an intolerable situation — has two facets.  One is a denial of reality: a reaction that something can't be true, that it is not possible.  The other is a denial of the unacceptable: a reaction that something is not normal, that although it exists it should not.  Both facets are involved in the denial of the reality of HIV/AIDS."  Nobody denies that an epidemic of poverty and disease exists in South Africa and they go hand-in-hand.  The "controversies" are: Is the disease caused by a retrovirus and is it sexually transmitted?

 

Sexual Transmission of HIV

In the first study conducted in gay men to examine the relationship between AIDS and sexual activity (before HIV was accepted as the cause of AIDS), the authors reported "…the number of partners per month in receptive anal-genital intercourse with ejaculation, the number of occasions of "fisting",…were the only independent and statistically significant variables for discriminating patients from controls".1  In 1984, Robert Gallo and his colleagues wrote "Of eight different sex acts, seropositivity correlated only with receptive anal intercourse…and with manual stimulation of the subject's rectum (receptive "fisting")…and was inversely correlated with insertive anal intercourse."2  Two years later they confirmed their 1984 findings: "In this analysis, only receptive rectal intercourse, douching, rectal bleeding…were significant predictors (p<.05) of anti-HTLV-III positivity…We found no evidence that other forms of sexual activity contributed to the risk."3  In a 1994 review of all the major studies conducted in gay men including the longest, largest, best-designed and executed published study of gay men anywhere in the world, the MultiCenter AIDS Cohort Study, the authors concluded:

"(1) unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection;  (2) anogenital insertive intercourse poses the highest risk for the sexual transmission of HIV-1 infection;  (3) there is mounting epidemiologic evidence for a small risk attached to orogenital receptive sex,…(4) sexual practices involving the rectum and the presence of (ulcerative) STD facilitate the acquisition of HIV-1;  (5) no or no consistent risk for the acquisition of HIV-1 infection has been reported regarding other sexual practices such as anogenital insertive intercourse and oroanal sex…".4

 

Since the main and absolutely necessary property of sexually transmitted agents is bidirectionality, that is, transmission from the passive to the active partner and vice versa, this means HIV cannot be sexually transmitted.

 

One of the first case reports of heterosexual transmission was published by Luc Montagnier and his associates in 1985.  The wife of an HIV positive haemophiliac who practised vaginal, oral and anal intercourse was found to be seropositive and to have low T4 cells.  She was followed for ten months after exposure to her husband's semen was discontinued.  When retested her T4 cells were normal and had a negative antibody test.5   In one of the largest prospective studies conducted in HIV positive haemophiliacs and their spouses, no women seroconverted.  The authors "calculated that in 11 couples unprotected vaginal intercourse occurred a maximum of 2,250 times (minimum 1,563) without transmission of HIV".6  In a similar study, the authors concluded "The most likely value of the probability of infection within 25.8 months for this group of 36 sexual partners is zero…The absence of seropositivity in any of the 36 sexual partners included in this study indicates that heterosexual transmission in this group with no additional risk factor is uncommon."7  The Padian et al study (the longest, largest, best-designed and executed published study of heterosexuals anywhere in the world) consisted of two parts, a cross-sectional and a prospective.  In the prospective study, despite the fact that even at the end of the study 25% of the couples were not "consistently" using condoms, no HIV transmission was reported.  In the cross-sectional part, in 10 years they reported only two cases of female-to-male transmission, but the authenticity of both was questioned by the authors themselves.  There were more cases of male-to-female transmission and in these cases "Anal intercourse significantly discriminated between seronegative and seropositive women";8 "…only the practice of anal intercourse (p = .003) and non-white race (p = .015) were significantly associated with infection".9  In the largest European study (9 centres from 6 countries) "The only sexual practice that clearly increased the risk of male-to-female transmission was anal intercourse…no other sexual practice has been associated with the risk of transmission".10

 

In the most recent analysis of heterosexual transmission, the authors wrote: "Though heterosexual intercourse has been virtually the sole explanation offered for the AIDS epidemic in sub-Saharan Africa, to our knowledge in no other part of the world has penile-vaginal exposure (as opposed to 'heterosexual sex') been demonstrated to initiate or sustain rapid HIV propagation.  HIV is not transmitted by 'sex', but only by specific risky practices…Dispassionate assessment of our conclusions admittedly depends on a willing suspension of disbelief, since the current paradigm is deeply embedded".11  Last year in this journal we presented evidence that in Africa there is no more heterosexual transmission than anywhere else in the world.12  One of the most eminent HIV experts, Jaap Goudsmit, acknowledges that for heterosexual HIV transmission "…a homosexual or anal factor seems to be required…Studies in Thailand showed that even frequency of intercourse did not promote the transmission of HIV-1B, as long as the intercourse was vaginal not anal…Limited studies of heterosexual couples in Africa suggest a parallel…".13

 

In conclusion at present there is ample epidemiological evidence which shows that:

(a)   The only sexual act, in both gay and heterosexual sex, which is related to the appearance of AIDS and a positive antibody test is receptive anal intercourse.

(b)   It is not homosexuality per se but the sexual act ("anal intercourse may be practiced by a much larger absolute population of heterosexuals than of homosexuals"14) which is important.  Thus, like pregnancy, AIDS and a positive antibody test can be sexually acquired but not sexually transmitted.  The difference is that while pregnancy can be acquired by a single act of sexual intercourse, for AIDS to appear a very high frequency of receptive anal intercourse over a long period is necessary.12

 

HIV Antibody Tests

The only test routinely used to prove HIV infection is the antibody test.  In clinical practice such a test cannot be used unless it is first proven specific.  In the HIV antibody test literature it is claimed that the tests are either 100% specific or they approach this accuracy.  The same literature also shows that the specificity has been determined by: comparing one antibody test with another;  testing known positive and negative samples;  testing young healthy blood donors.  Basic scientific methods rule out specificity being determined in this manner.  Only comparing the reactivity with the presence or absence of HIV will determine the specificity of the antibody tests.  That is, HIV isolation/purification must be used as the gold standard for the antibody tests.  However, at present some of the best known HIV/AIDS experts agree there is no such gold standard.  "One difficulty in assaying the specificity and sensitivity of human retroviruses [including HIV] is the absence of a final 'gold standard'".15 16  According to one antibody test manufacturer "At present there is no recognized standard for establishing the presence or absence of antibodies to HIV-1 and HIV-2 in human blood…Specificity based on an assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in random donors…is estimated to be 99.90%…".17  The specificity of the Western Blot (WB), the test which is used as a gold standard for all the other antibody tests as well as for the PCR test,18 19 cannot be determined even if a gold standard exists.  This is because the WB is not standardised20 21  (see www.theperthgroup.com/aids/WBCHART.pdf ).  It follows that the specificity may be anywhere between 0% and 100%.

   

In the vast majority of studies conducted in Africa the authors do not even follow the algorithms recommended by the manufacturers. One example is the latest and largest study conducted in South Africa and said to have shown that "South Africa has the highest number of people with HIV in the world", "five million people infected".  The manufacturer of the test used in this study points out that the test cannot be used to prove HIV infection but only as a screening test to be confirmed by WB.  Furthermore, the "OraSure© HIV-1 Oral Specimen Collection Device is intended for use in the collection of oral fluid specimens for testing for antibodies to the Human Immunodeficiency Virus-Type 1 (HIV-1) in subjects 13 years of age and older".22 23  Yet the test (a single ELISA without a confirmatory test) was used to test all individuals including children aged between 2 and 13 years and the results were interpreted as proving that 11.4% of South Africans are HIV infected.24

 

In addition, the antigens used in the antibody tests may not even be HIV proteins.  According the discoverer of HIV, Luc Montagnier, to characterise the HIV proteins the virus must be purified.  Although in 1983 he and his group claimed to have done so and to have obtained the HIV proteins from the "purified" virus, in 1997 he admitted that even after "Roman effort", in electron micrographs of their "purified" virus they could not see any particles with the "morphology typical of retroviruses."25  This means that the "HIV" proteins could not have been those of a retrovirus, HIV.  By 1997 some of the best known HIV experts pointed out that HIV "used for biochemical and serological analyses or as immunogens is frequently prepared by centrifugation through sucrose gradients", but in none of the studies "the purity of the virus preparation has been verified".26 27  In other words, up till 1997 nobody had published electron micrographic proof that the "purified virus" contained nothing else but isolated retroviral particles.  In that year two studies were published, one by a US team and the other a Franco-German collaboration.  The authors of both studies claimed that their "purified" material contained some particles that were HIV particles.  However they admitted that their material predominantly contained "budding membrane particles frequently called microvesicles" or "mock virus".  In other words, the "HIV" proteins have been and still are obtained from particulate material which consists overwhelmingly of cellular fragments in which are interspersed a small number of particles whose morphology more resembles that of retrovirus particles but none of which have all the structural characteristics attributed to HIV or even to retrovirus particles.26 27

 

The minimum absolutely necessary but not sufficient condition to claim that what are called "HIV-1 particles" are a retrovirus and not cellular microvesicles is to show that the sucrose density fractions obtained from the infected cells, the "purified virus", contain proteins which are not present in the same fractions obtained from non-infected cells, the "mock virus".  However, this is not the case.  The only difference one can see in the SDS-polyacrylamide gel electrophoresis strips of "purified virus" and "mock virus" is quantitative, not qualitative.  This means that the same proteins are present in the "purified virus" and "mock virus".  In other words, the antigens in the antibody tests could be nothing more than cellular proteins, a problem which has been known for many years.

 

In 1983, Montagnier and his colleagues found a protein p45 (p41) in their "purified" virus and the protein reacted with antibodies present in the patient's sera.   They concluded that the protein was not viral but the cellular protein actin,28 a view still held by Montagnier.29  At present, some of the best known HIV experts acknowledge that the proteins with molecular weight of approximately 41,000 present in the "purified HIV" are in fact actin.30  In 1989 researchers from New York showed that p120 and p160 in the "purified virus" are oligomers of p41.31

 

In 1987  Henderson isolated the p30-32 and p34-36 of "HIV purified by double banding" in sucrose density gradients.  By comparing the amino-acid sequences of these proteins with Class II histocompatability DR proteins, they concluded that "the DR alpha and beta chains appeared to be identical to the p34-36 and p30-32 proteins respectively".32 That these proteins are cellular is acknowledged by other HIV experts.30

 

Since the antigens present in the antibody test kits are normal cellular proteins, it follows that they will react with auto-antibodies.  They may also cross-react with other antibodies including HIV which may be present in the sera.  However the only way to prove that HIV antibodies are present in any sera is by using HIV as a gold standard which to date has not been done.  Until this is achieved, the HIV prevalence in South Africa cannot be ascertained — it could be anything from zero to five million.

 

This does not mean there is no relationship between a positive "HIV" antibody test, whatever its genesis, and the risk of developing AIDS.  In fact there can be no doubt that in the risk groups many studies have proven this an undisputed fact.  However, at present there is no proof that the reason for being seropositive is HIV.  A positive antibody test may be no more than a non-specific marker reflecting a propensity to develop certain illnesses.  In this manner it can be regarded as having similar clinical utility to measurements of the erythrocyte sedimentation rate (ESR).  The ESR, although archetypically non-specific, is highly indicative or predictive of morbidity and mortality.  In fact the ESR is a far better predictor of AIDS than the CD4 count despite the fact the latter is accepted to be the cause of the clinical AID syndrome.21 33

 

We agree with Fassin and Schneider "to widen the debate and hence to increase understanding of the epidemic" in South Africa.    However, as well as debating the "social epidemiology of HIV", the debate must be preceded by or at least be concurrent with the "biomedical and behavioural" debate.    Once it is irrefutably proven that HIV has indeed infected 5 million or any number of South Africans as a result of heterosexual transmission or by any other means, then it would be useful to pursue the "social epidemiology of HIV".

 

Eleni Papadopulos-Eleopulos  Biophysicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

 

Valendar F. Turner  Consultant Emergency Physician, Department of Emergency Medicine, Royal Perth Hospital, Perth, Western Australia

 

John M Papadimitriou  Professor of Pathology, University of Western Australia, Perth, Western Australia

 

Barry A. P. Page  Physicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

 

Sam Mhlongo  Head & Chief Family Practitioner, Family Medicine & Primary Health Care, Medical University of South Africa, Johannesberg, South Africa

 

Helman Alfonso  Department of Research, Universidad Metropolitana Barranquilla, Colombia

 

David Causer Physicist, Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia

 

Christian Fiala  Gynaecologist, Mollardgasse 12a A-1060 Vienna, Austria

 

Anthony Brink  Advocate of the High Court of South Africa

 


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33. Lefrere JJ, Salmon D, Doinel C, Rouger P, Courouce AM, Lambin P, et al. Sedimentation rate as a predictive marker in HIV infection. AIDS 1988;2:63-4.

Competing interests:   None declared


POVERTY, SQUALOR & AIDS INDISTINGUISHABLE IN SOUTH AFRICA: MBEKI MISUNDERSTOOD AND MISREPRESENTED 14 March 2003
Sam WP Mhlongo,
Head of Department Family Medicine & Primary Health Care, Medunsa
Medical University of Southern Africa, 0204 RSA

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Re: POVERTY, SQUALOR & AIDS INDISTINGUISHABLE IN SOUTH AFRICA: MBEKI MISUNDERSTOOD AND MISREPRESENTED

Although the title "The politics of AIDS in South Africa: beyond the controversies" (Fassin & Schneider BMJ Vol. 326, March 1st 2003) is eye-catching, the piece has a number of disturbing inaccuracies, polemics and has failed to live up to the title. The article remains firmly rooted in the controversy and invitingly implores the question: what is the cause of AIDS in Africa? The authors have clearly made up their minds and without any shadow of doubt that HIV is the cause of AIDS in Africa and that heterosexual transmission is the dominant mode in the infection process. It s hardly surprising that they have failed to go beyond the controversies - hence HIV appears no less than 22 times in their article.

In their first paragraph, Fassin and Schneider claim that President Mbeki sent a letter to world leaders expressing his doubts that HIV was the exclusive cause of AIDS '.1 There is no reference for this 'letter' of Mbeki's to these anonymous world leaders. Fassin and Schneider deliberately mislead by misrepresentation of President Mbeki's position of 1999. As far as the facts stand at the moment, there is no evidence whatsoever to suggest that Mbeki has changed from his 1999 position. He still has the same questions, which are: Why is AIDS in Africa so vastly different from AIDS in Western Europe and North America? why is the mode of transmission predominantly heterosexual in Africa? How safe is the drug Zidovudine? When Mbeki failed to get a response to these questions from his scientists, he sought advice from outside South Africa from both orthodox and dissident scientists. This is how The Presidential AIDS Advisory Panel was formed in April 2000 consisting of 20 orthodox and 13 dissident scientists. 2 Mbeki's view is that science cannot be reconciled with national boundaries hence, the international nature of The Presidential AIDS Advisory Panel. Another misrepresentation in this article is that in April 2002, 'Mbeki formally distanced himself from "the AIDS dissidents". We are not given the evidence for this statement. The fact is: Mbeki has neither declared he was distancing himself from dissident nor orthodox positions on the subject of HIV/AIDS.

Slowly but inexorably evidence casting doubt on the orthodox assumption that in Africa, AIDS is overwhelmingly due to heterosexual transmission of HIV is emerging. Interestingly this evidence comes not from dissident but non-dissident scientists. The following from peer reviewed papers will illustrate this point:

a) Devon D. Brewer and his colleagues stated in their 2003 paper: 'We are aware of no study from sub-Saharan Africa suggesting cyclic sexual network architecture. Without evidence of appropriate network configurations on a scale considerably larger than that observed in developed countries, rapid propagation of HIV in Africa would be difficult to sustain ...... Dispassionate assessment of our conclusions admitted depends on a willing suspension of disbelief, since the current paradigm is deeply embedded......Finally, Africans deserve scientifically sound information on the epidemiological determinants of their calamitous AIDS epidemic'. 3

b) With regard to sexual or vertical transmission, David Gisselquist et al have thrown wide open the discussion regarding the cause(s) of AIDS in Africa and concluded that: "The recognition that significant proportions of HIV in African adults and children cannot be explained on the basis of current knowledge about sexual and vertical transmission leaves open several transmission hypotheses" 4 In short, this must necessarily mean re-examination of the current hypothesis and assumption that the mode of HIV transmission in Africa is largely heterosexual activity. In addition the validity of the tests for HIV antibodies need to be questioned in addition to questioning poor hygiene practices in African health care services.

c) To date, the longest epidemiological study questioning heterosexual transmission is that of Nancy Padian and colleagues over a period of ten years. In their paper (Heterosexual Transmission of Human Immunodeficiency Virus (HIV) in Northern California: Results from a Ten- Year Study, Padian and her colleagues concluded that with regard to male to female transmission (0.0009 per contact), it would take 770 or 3333 sexual contacts respectively to reach a 50% or 95% probability of becoming infected. Based on Padian's estimate of female-to-male transmission, it would require 6200 and 27000 contacts and a period of 51 and 222 years respectively. 5

Fassin's and Schneider's reference to The Constitutional Court judgement on the provision of antiretrovirals has an air of triumphalism about it. It can be argued that this was not a judgement on science but a judgement dictated to by populism and national emotions about HIV/AIDS. In the midst of all this, physicians and medical scientists should rise above emotions and populist pursuits so that the public is made aware that the improvements in the health status of Western Europe and North America had very little to do with the provision of drugs. In the last two centuries the decline in the incidence of tuberculosis in these countries was not largely due to chemotherapy, but rather due to improved living conditions, sanitation, nutrition, employment and reduced family size- see figure showing mean annual death rates from TB in England and Wales. 6

Prof. Sam MHLONGO MBBS, MSc, LRCP, MRCS (London), MRCGP(UK)
Chief Family Physician & Specialist,
Head of Department of Family Medicine & Primary Health Care, Medical University of Southern Africa, MEDUNSA 0204, PRETORIA, SOUTH AFRICA

References:

1. Didier Fassin, Helen Schneider: The politics f AIDS IN South Africa: beyond the controversies: BMJ VOLUME 326 1 March 2003:495-497

2. Sam MHLONGO: HIV BLAMED FOR POVERTY: La medicina la psicanalisi la vita (PUBLISHED BY: SPIRALI/VEL 2000-MILAN)

3. Devon D Brewer et al: Mounting anomalies in the epidemiology of HIV in Africa: cry the beloved paradigm: International Journal of STD and AIDS 2003; 14:144-147

4. Gisselquist, Richard Rothenberg, John Potterat; Ernest Drucker. HIV infections in sub-Saharan African not explained by sexual or vertial transmission: International Journal of STD & AIDS 2002;13:657-666.

5. Padian NS et al (1997) Heterosexual Transmission of Human Immunodeficiency Virus (HIV) in Northern California: Results from a Ten- Year Study. American Journal of Epidemiology 1997;14:350-357.

6. Thomas Mckeown: The role of Medicine: Dream, Mirage or Nemesis: 92 - 96: Basil Blackwell: Oxford 1979)

Competing interests:   None declared


Studies showing LOW rates of heterosexual transmission do not support alternative AIDS theories... 15 March 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: Studies showing LOW rates of heterosexual transmission do not support alternative AIDS theories...

Works by Gisselquist and Padian are both cited above in support of alternative AIDS theories.

The Gisselquist article(1) (available on line he re) states that:

---
"Studies among African couples find low rates of heterosexual transmission, as in developed countries."
---

As you can read for yourself in the abstract, Gisselquist suggests that iatrogenic causes have been underestimated. If in this article (or any article by Gisselquist or any of his colleagues) you can find ANY suggestion that HIV doesn't cause AIDS or that it isn't transmitted sexually (at all) please let us all know.

As for the Padian paper(2) (available on line her e):

Padian's paper does not prove that HIV can't be transmitted sexually because:

Although there were no NEW transmissions during the study period:

1. All participants were aware that they were with a HIV-positive partner.

2. They all new that they were part of a study examining transmission.

3. It (might be) safe to assume that none of the participants wanted to be infected.

4. The group studied are all from a wealthy country which was saturated with AIDS education.

5. Condom use increased substantially during the study period.

6. Anal sex decreased substantially during the study period.

7. The whole world does not live in North Carolina.

References:

(1) Gisselquist D, Rothenberg R, Potterat J, Drucker E. HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. Int J STD AIDS. 2002 Oct;13(10):657-66. Review. PMID: 12396534. [A bstract]

(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15. [Ab stract]

Competing interests:   None declared


Time for the end of AIDS 18 March 2003
Ed Cooper,
Consultant Pediatrician
Newham General Hospital, London E13

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Re: Time for the end of AIDS

Why don't we get rid of AIDS? — the name, that is, the diagnostic designation. It has outlived its usefulness, in the same way that we no longer diagnose "consumption" but recognise an infection, tuberculosis. The analogy holds well: centuries ago individuals were recognised to be consumed, sometimes rapidly ("galloping consumption") by something related to their environment — damp, overcrowding — or perhaps their own constitution. Now we recognise Mycobacterium tuberculosis and see that the infection has a natural history varying by the passage of time, the nutritional state of the host, etc, etc. We are also less likely to misdiagnose "consumption" as we no longer rely on a constellation of symptoms and signs but make the detection of the micro-organism, or at least its protein, essential to confirmation of the diagnosis of tuberculosis.

The history of AIDS is well known: in 1981 in New York an unusual combination of symptoms was observed and its epidemic nature was soon seen. The only link among the effects was the loss of the host's immune control of parasites and mutant cells. Based on the resemblance to the genetically mediated congenital immunodeficiencies, the entity Acquired ImmunoDeficiency Syndrome was born. Both the definition and the risk factors of the new syndrome were revised repeatedly. A virus was later identified. The virology has been elucidated in unusual detail and with great consistency, and its nature as a retrovirus fits with advances in cellular biology on the broad front of scientific research around it. The natural history of infection with this virus has been observed thoroughly. It often culminates in that list of characteristics that meets whatever is the current definition of AIDS. But neither a bedside diagnosis of AIDS, nor a bedside diagnosis of galloping consumption, are as reliable as the laboratory diagnosis of HIV infection, or M. tuberculosis infection.

The argument about whether the characteristics of AIDS in Africa are identical to those in North America is sterile. Not every failure of immunity is mediated by HIV. All diseases, like cancer, vary in symptomatology. The model molecular disease, sickle cell disease, homozygous hemoglobin S, has an invariant genotype and a widely variable phenotype.

But Africa and North America do share an infectious disease. Could it be called immunoretrovirosis (IRV)? The agent is HIV. It is epidemic and dangerous, ultimately lethal. It occurs in Africa. President Mbeki should stop worrying about whether HIV causes AIDS, but worry about the epidemic of immunoretrovirosis around him. We all need to work on the known preventive and treatment measures to control this viral infection. We do not need the acronym AIDS.

Competing interests:   None declared


Low rates of heterosexual transmission and the HIV theory of AIDS 24 March 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia 6009,
Valendar F. Turner, John M Papadimitriou, Barry A. P. Page, Helman Alfonso, David Causer, Sam Mhlongo, Anthony Brink

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Re: Low rates of heterosexual transmission and the HIV theory of AIDS

We agree with Tony Floyd that "Studies showing LOW rates of heterosexual transmission do not [necessarily] support alternative AIDS theories…" Now the vast majority of people (millions) who are said to be HIV positive are said to have acquired it through sex. This is not possible if the transmission is zero or even low which means that either HIV was acquired by means other than sex or the HIV antibody test is non- specific and thus they are not infected.

According to Gisselquist and his colleagues "HIV is not transmitted by 'sex', but only by specific risky practices"1, that is, passive anal intercourse.2 It is also our view that a positive antibody test ("HIV") is acquired by the same means, that is, passive anal intercourse. But no proof exists that it can be transmitted to the active partner.

The Padian study is considered to be the best study of its type in which the author vigorously strived to prove heterosexual transmission. We would be interested to be shown where in the Padian study ("the study in which "Condom use increased substantially during the study period", and yet EVEN AT THE END OF THE STUDY 25% of couples were not consistently using condoms) is there proof that HIV can be sexually transmitted. Alternatively, is there any prospective study which PROVES bidirectional sexual transmission of HIV?

We can understand Tony Floyd's comment in his extensive online debate with David Rasnick and Rodney Richards "Can you blame me for being sceptical given the plethora of other errors in attempts to support alternative AIDS theories?" Instead of simply pointing out errors on either side and accepting or dismissing what the authors claim, a return to basic principles is needed.

In HIV/AIDS the two cornerstones are the antibody test and sexual transmission. If the specificity of the antibody test is not determined as David Rasnick stressed in the debate, everything else is totally irrelevant. To claim proof for the specificity there MUST BE at least one study and a few confirmatory studies where the antibody antigen reaction (assuming that the antigens are HIV) is compared with the presence or absence of HIV, that is, with HIV isolation/purification. This study must include a statistically significant number of both patients who have AIDS as well as patients who do not have AIDS but are sick. In addition, the tests must performed blind.

Any study claiming proof for heterosexual transmission MUST satisfy at least the following conditions:

• Be prospective
• Use tests which have been proven to be specific
• Have a statistically meaningful population
• The results must be statistically significant and must exclude any other possible route of infection

Until at least these two basic issues are resolved, scientists have no option but to question the HIV theory of AIDS.

References

1. Brewer DD, Brody S, Drucker E, Gisselquist D, Minkin SF, Potterat JJ, et al. Mounting anomalies in the epidemiology of HIV in Africa: cry the beloved paradigm. International Journal of STD and AIDS 2003;14:144-147.

2. Brody S, Lack of evidence for transmission of human immunodeficiency virus through vaginal intercourse. Arch Sex Behav 1995; 24(4):383-393.

Competing interests:   None declared


Neither Padian, Gisselquist or Brody provide any reason to believe HIV isn't sexually transmitted... 26 March 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Neither Padian, Gisselquist or Brody provide any reason to believe HIV isn't sexually transmitted...

It has been stated above that the Padian paper(1) does not PROVE that heterosexual transmission occurs.

No argument there.

My point is that it doesn't PROVE that heterosexual transmission of HIV DOESN'T occur. As has been acknowledged, condom use did decline during the study period (although as many as 25% of the participants still admitted to inconsistent use by the end of the study period.)

I'll stand by my reasons as to why Padian's paper does not prove that HIV can't be transmitted sexually:

Although there were no NEW transmissions during the study period:

---
1. All participants were aware that they were with a HIV-positive partner.

2. They all new that they were part of a study examining transmission.

3. It (might be) safe to assume that none of the participants wanted to be infected.

4. The group studied are all from a wealthy country which was saturated with AIDS education.

5. Condom use increased substantially during the study period.

6. Anal sex decreased substantially during the study period.

7. The whole world does not live in North Carolina.
---

It is also claimed above that:

According to Gisselquist and his colleagues "HIV is not transmitted by 'sex'...

REALLY??? Where is that written?

Unless you can get Gisselquist or one of the other researchers to confirm such a comment, one can only go by what they have put into print.

For example in a letter right here in the BMJ(2) (in the final paragraph):

---
"Although cofactors such as sexually transmitted diseases and lack of circumcision may boost heterosexual transmission..."
---

Sure, he is questioning if non-sexual transmission has been overlooked, but he does comment on factors BOOSTING heterosexual transmission!.

Stuart Brody is also cited, and his 1995 paper does state that intravenous and anal activities remain the only clear vectors for HIV transmission.

Does Brody still hold this view now?

His 1997 book(3) refers to the Low AIDS Risk of Vaginal Intercourse.

Not no risk, low risk. AND he is referring to a low risk in modern countries, where the presence of cofactors such as other sexually transmitted diseases(2) is much lower.

References:

(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15. [Abstract]

(2) Gisselquist D, Rothenberg R, Potterat J, Drucker E. Non-sexual transmission of HIV has been overlooked in developing countries. BMJ. 2002 Jan 26;324(7331):235.

(3) Brody S. Sex at Risk: Lifetime Number of Partners, Frequency of Intercourse, and the Low AIDS Risk of Vaginal Intercourse. New Brunswick, NJ: Transaction Publishers, 1997: 109—168 [amazon.com Link]

Competing interests:   None declared


Is There Proof for Heterosexual Transmission of HIV? 27 March 2003
Eleni Papadopulos Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia,
Barry Page, Valendar Turner, John Papadimitriou, David Causer, Helman Alfonso

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Re: Is There Proof for Heterosexual Transmission of HIV?

Is There Proof for Heterosexual Transmission of HIV?

We put two basic questions to Tony Floyd: 1. Where is the evidence that proves the HIV antibody tests are specific? 2. Where is the evidence that proves HIV is heterosexually transmitted?

He answered neither.

Heterosexual transmission of HIV can only be accepted if studies provide evidence which prove it. It is fallacious to state that the Padian study "doesn't PROVE that heterosexual transmission of HIV DOESN'T occur."

Concerning the quote from Gisselquist and his colleagues "HIV is not transmitted by 'sex'…", please read the first sentence of paragraph 2 of the conclusion the authors reached in their paper published in 2003 (Brewer, et al Int J STD & AIDS 2003; 14:144-147) which is reference 1 in our previous rapid response.

Tony Floyd asks: "Does Brody still hold this view now?" (that "intravenous and anal activities remain the only clear vectors for HIV transmission.") The answer is in the affirmative and is found again in the first 2 sentences of paragraph 2 of the conclusion in their paper published in 2003 (Brewer, et al Int J STD & AIDS 2003; 14:144-147) which is reference 1 in our previous rapid response.

Perhaps Tony Floyd has no answer to our two basic questions listed above.

Competing interests:   None declared


Heterosexual anal intercourse. A severely underestimated mode of HIV transmission? 28 March 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: Heterosexual anal intercourse. A severely underestimated mode of HIV transmission?

>We put two basic questions to Tony Floyd: 1. Where is the evidence that proves the HIV antibody tests are specific? 2. Where is the evidence that proves HIV is heterosexually transmitted?

> He answered neither

Yes, but you asked me neither.

What you asked was:

> Until at least these two basic issues are resolved, scientists have no option...

You asked 'scientists'. Not I. Will the ability of Tony Floyd (or any other medical student) to answer such questions be the sine qua non of Evidence Based Medicine going forward?

Crikey.

What I did provide was seven reasons as to why the Padian paper doesn't disprove heterosexual transmission of HIV. That's all. There was no open challenge issued regarding all questions posed to scientists in general.

What is meant by heterosexual transmission anyway? In a survey of University Students(1) it was found that:

"Almost 23% of nonvirgin students had engaged in anal intercourse"

In a review of heterosexual anal intercourse by Halperin(2) it was concluded that:

"This typically stigmatized and hidden sexual practice must be given greater emphasis in AIDS/STD prevention, women's care, and other health promotion programs"

Perhaps heterosexual anal intercourse is a severely underestimated mode of HIV transmission?

As for Gisselquist and Brody (who are again cited in support of alternative AIDS theories) could you please provide the URL or PMID number for the study referred to (or any study) by these two researchers that supports any theory that HIV can't be transmitted heterosexually?

In the absence of such evidence I can only assume that Gisselquist and Brody continue to support the fact that HIV can be transmitted by heterosexual contact as evidenced by their article(3) and book(4) respectively.

References:

(1) Baldwin JI, Baldwin JD. Heterosexual anal intercourse: an understudied, high-risk sexual behavior. Arch Sex Behav. 2000 Aug;29(4):357-73. PMID: 10948725 [Abstract]

(2) Halperin DT. Heterosexual anal intercourse: prevalence, cultural factors, and HIV infection and other health risks, Part I. AIDS Patient Care STDS 1999 Dec;13(12):717-30 [Abstract]

(3) Gisselquist D, Rothenberg R, Potterat J, Drucker E. Non-sexual transmission of HIV has been overlooked in developing countries. BMJ. 2002 Jan 26;324(7331):235. [Abstract]

(4) Brody S. Sex at Risk: Lifetime Number of Partners, Frequency of Intercourse, and the Low AIDS Risk of Vaginal Intercourse. New Brunswick, NJ: Transaction Publishers, 1997: 109—168 [amazon.com Link]

Competing interests:   None declared


More reasons for low heterosexual transmission in the Padian study 30 March 2003
Peter Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK FY3 8NR

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Re: More reasons for low heterosexual transmission in the Padian study

Tony Floyd (26th March) lists several reasons why Padian's heterosexual transmission study showed a low transmission rate.

There are two further important reasons. Padian recruited HIV discordant couples for the prospective part of her study.

Firstly, this means that the participants were self-selected as NOT having already acquired HIV infection from their previously infected partners. We know there are some index cases who are "poor transmitters" and similarly some people are more resistant to HIV-acquisition than others. Since Padian's study subjects had all indulged in the risky activity in question (sex) for considerable periods of time prior to joining the study, there is very likely to be a bias towards couples who were unlikely to pass on/catch HIV in any circumstance.

Secondly, we also know that HIV is maximally infectious during the acute phase of infection, and that many if not most transmissions occur during this period. All of Padian's study subjects had passed through this time frame (without experiencing any HIV transmission) before entering her study.

If an HIV seronegative individual is going to acquire HIV heterosexually, it is far more likely to happen within the few weeks after their partner has caught HIV themselves.

It stands to reason that Padian's study subjects were at substantially lower risk of HIV transmission than would be expected in a "real-life" scenario.

Competing interests:   None declared


So, where is the evidence? 1 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: So, where is the evidence?

Dear Editor,

In trying to explain the Padian et al. inability to detect HIV negative individuals becoming HIV positive after years of unprotected sexual intercourse with HIV positive partners, Peter Flegg says that, "If an HIV seronegative individual is going to acquire HIV heterosexually, it is far more likely to happen within the few weeks after their partner has caught HIV themselves." Perhaps. But, where is the evidence published in the scientific, medical literature that HIV is indeed sexually transmitted, whether early or late in infection? Flegg seems to agree that the Padian et al. study [1] does not provide that proof. So, where is it to be found?

In addition, if one accepts Flegg's argument, then it raises a serious problem for the contagious/HIV hypothesis of AIDS. If, as Flegg says, after a short time following infection an HIV positive individual eventually fights off HIV and is thus unable to spread the infection, then by definition that individual has become immunized against HIV. That is precisely what having antibodies to HIV signifies. That is also why it is impossible to measure an infectious titer in HIV positive individuals. In other words, HIV behaves exactly like any other virus in that it rapidly produces an strong immune response and is very quickly eliminated in healthy people without a trace of infectious virus.

So, Flegg has unwittingly raised yet another serious problem--how does HIV cause AIDS if it is so rapidly and efficiently eliminated by the immune system? This compels me to ask Flegg, what are the names of the individuals who are documented to have shown how HIV causes AIDS? Failing that, what are the names of the people who have shown that HIV even causes AIDS, regardless of mechanism?

When I have asked this question in the past, the usual response is that there are too many names to list. So, please just list the first individuals, along with their potentially Nobel prize-wining publications.

David Rasnick

1. Padian, N. S., et al. (1997) Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study, Am J Epidemiol 146, 350-357

Competing interests:   None declared


Clarification of the basic issues in relation to the HIV theory of AIDS 1 April 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, David Causer, Barry Page, Helman Alfonso

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Re: Clarification of the basic issues in relation to the HIV theory of AIDS

Let us clarify the basic issues concerning the HIV theory of AIDS

It is not necessarily a problem that perhaps Tony Floyd or anybody else including scientists such as immunologists and retrovirologists may lack knowledge regarding the two basic issues of the HIV theory of AIDS. However, it becomes a problem when such individuals spare no effort to promote the HIV theory of AIDS. The relevant references are readily available to all including medical students with their young and sharp minds.

As far as the Padian study is concerned, it is irrelevant whether there are 7 reasons or more (we note that Peter Flegg gives 2 more reasons in his rapid response "More reasons for low heterosexual transmission in the Padian study", 30th March 2003) "why the Padian paper doesn't disprove heterosexual transmission of HIV." For heterosexual transmission of HIV to be accepted proof must exist, provided by either Padian or anybody else, that this takes indeed place. Would Tony Floyd have us believe that Martians exist because nobody has proven they don't?

We are glad Tony Floyd agrees with us that "anal intercourse is a severely underestimated mode of HIV transmission". If he puts some effort into reading some of the references we have provided in our first rapid response "HIV in Africa" (13th March 2003), he will come to the conclusion that all the presently available data prove it is only passive anal intercourse which is the risk factor for the acquisition of a positive antibody test. In other words, a positive "HIV" antibody test like pregnancy can be sexually acquired but cannot be sexually transmitted.

So again we ask, "Is there proof for heterosexual transmission of HIV?" and where is there proof of the specificity of the antibody tests?

Competing interests:   None declared


For some people its April Fool's day all year round 3 April 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK FY3 8NR

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Re: For some people its April Fool's day all year round

It seems that I have joined the ranks of those who have been deliberately misquoted or misinterpreted. Any day now, David Rasnick will be labelling me as a "mainstream HIV dissident". I do not know whether to feel flattered to join the likes of Nancy Padian and other foremost HIV researchers, or angry. Seeing as how Rasnick's letter misquoting me was written on April fool's day, maybe I should take it all with good humour.

Seriously, though, his statment cannot go uncorrected (1st April 2003). Once again he has either failed to comprehend what I have said, or more likely, deliberately reinterpreted it to make it seem as though I have said something which I have not.

To make things absolutley clear, I do not "agree" with him that the Padian study shows no proof of HIV being sexually transmitted. I explicitly stated that "there was a low transmission rate" in her study, and gave two pertinent reasons additional to those provided by Floyd as to why that may have been the case.

Also, nowhere have I said "following infection, an HIV positive individual eventually fights off HIV and is thus unable to spread the infection". I insist Rasnick correct his statement to this effect that I said this. What I have done is to point out that HIV is more efficiently transmitted in the acute phase of primary infection than it is subsequently. There is plenty of data verifying this, both epidemiologically and biologically, and if he wants references I will be glad to provide these. I would however remind Rasnick that HIV is a chronic infection, and the cumulative probability of transmission of virus increases with the duration of exposure. This is the same situation that exists with other latent viral infections.

I am still perplexed as to what the dissidents think about HIV. We are constantly exposed to a chaotic mish-mash of mutually-exclusive theories concerning HIV/AIDS. One moment we are asked to believe there is no such thing as HIV (or antibodies to it), the next that there is but it is totally harmless, then that it causes infection but cannot cause immunodeficiency. What makes matters worse is that the dissidents are so inconsistent that they will shift from one opinion to another whenever it suits their argument. We thus have the schizophrenic spectacle of someone like Rasnick championing the concept that HIV antibody tests are meaningless, and then to go on to claim that antibodies to HIV indicate immunity to it. Or someone like Eleni Papadopulos-Eleopulos asserting that HIV does not exist, only to claim later that it spreads through anal intercourse.

Rasnick seems to imply (note — I make no assumptions, since dissidents can mean several things at the same time!) that HIV exists, since he says it is a virus that causes acute infection that is eliminated by the immune system, leaving people immunised against it. For his information, with chronic latent infections, possession of antibodies does not mean elimination of the agent and subsequent immunity to its effects. If it did, this would require a immunological rethink would shake the world of biological sciences to its core. However, his novel concept may come as welcome news to all those patients with chronic viral infections such as hepatitis B and C, Herpes simplex, HTLV-1, CMV, EBV, etc. as well as all those with untreated bacterial and parasitic infections such as borrelia, brucella, syphilis, toxoplasma, malaria, leishmania, bilharzia, etc. They can all relax, they have antibodies! They are immune and have eliminated their infections forever!

Competing interests:   None declared


Wake up call and need for paradigm shift 3 April 2003
Felix ID Konotey-Ahulu,
Kwegyir Aggrey Distinguished Professor of Human Genetics, University of Cape Coast, Ghana
Consultant Physician, Department of Tropical Medicine, Cromwell Hospital, London SW5 0TU

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Re: Wake up call and need for paradigm shift

Education and debate

One African's Response

AIDS in South Africa

Wake up call and need for paradigm shift

I present my point-by-point response to Didier Fassin and Helen Schneider1, the value of whose article cannot be overestimated. They have gone farther than anybody in their diagnosis of what is happening with AIDS in South Africa in particular, and Sub-Saharan Africa in general.

President Thabo Mbeki's Stance on HIV/AIDS in South Africa

"President Mbeki's stance on the epidemic"1 was influenced by Professor Peter Duesberg who is credited for having initially mapped the genetic structure of retroviruses. Thabo Mbeki has been roundly condemned for putting Peter Duesberg, the apostle of 'AIDS Dissidents', on his panel of experts convened to advise him about "AIDS in Africa: the way forward"2.

Twelve years ago, The Heritage Foundation, invited 11 people around the world to examine the thesis of Peter Duesberg and Bryan Ellison and present their critique for publication. The thrust of Duesberg's thesis was that HIV was not the main cause of AIDS. I was one of the eleven, approached on the basis of first-hand experiences of what was happening in Africa.3-14 I was sent Duesberg and Ellison's paper which said "retroviruses are poor candidates to blame serious diseases on,"15 and that poverty, drugs, immunosuppressive behaviour, and certain "risk factors", singly or in combination, could produce AIDS. The condition, they said, was not infectious and that it failed 'Koch's postulates' test. I was charged with examining this thesis in the light of what was happening in Africa in general, and in my Krobo tribe in particular.

I knew a town where generations had been eating green monkey meat (with their retroviruses) for centuries. The only few AIDS patients in the town were females who had just been sent home to die, from Abidjan where they had gone for the sex trade.3 10 11 Duesberg could be right after all; eating green monkeys did not make HIV jump the species barrier, and if it did it was innocuous.

Searching Parameters for examining Peter Duesberg's Thesis

I chose 13 socio-clinical parameters and examined each one in the light of Duesberg against what was happening in Africa.3 10-12 Of the 13, Duesberg and Ellison were wrong in 6, and could be vindicated in seven.16 "In summary", I concluded, "there are 'pluses' and 'minuses' in the Duesberg and Ellison hypothesis…"16 One of the 6 parameters I failed Duesberg on16 was when he said HIV was not infectious.15 If such a world authority maintained that a retrovirus was not infectious and I said it was,16 then were we talking about the same thing?

Another Explanation?

Duesberg might be talking about naturally occurring retroviruses, while the 'HIV' I knew was wreaking havoc out there might not be natural at all — it could be artificial, as the astute English physician, Dr John Seale, pointed out in the world's leading scientific journal Nature that first published the DNA structure. Seale's short, but brilliant, communication was called "Artificial HIV?"17 Another English physician, Dr Victor Daniels stated: "The origins of the immunodeficiency virus are not totally clear. It has been suggested, but not confirmed that the virus has been man-made in the Soviet Union or United States as a weapon of biological warfare."18 Writing under the title "The Biological Bomb" The Lancet gave this definition: "Biological warfare is the intentional use of living organisms or their toxic products to cause death, disability, or disease in man, animals, or plants or to poison food-supplies ('public health in reverse')"19 and that there was a "biological bomb lying at the heart of the cellular nucleus, ticking us to destruction."19 At the same Lancet symposium, Lord Ritchie-Calder said: "While one group of scientists is devoting its energies to prevent diseases, another is devising man-made epidemics."19 In their instructive article, Fassin and Schneider revealed: "As has recently been shown, in the last years of apartheid government laboratories were developing chemical and biological weapons (including anthrax, intended to eliminate black leaders), .."1 Just the type of biological bomb Lancet wrote about 35 years ago19?

HIV versus 'HIDDNA'

To understand the difference between the natural "retrovirus-HIV" Duesberg and some 'AIDS Dissidents' called "Science Fiction"15, and the real cause of Lancet's "man-made epidemics"19 I now suggest the perception of 'HIV' as some hidden agent (hidd'n agent), 'HIDDNA' which term I have coined to stand for "Human Immune Deficiency DNA", specially fashioned in an apartheid laboratory ("intentional use of living organisms"19) to attack the immune system for biological warfare since we are now told that some such research was going on in South Africa.1 Has South Africa been hit by a biological bomb?

Paradigm Shift in thought and approach is required to tackle the AIDS problem

The answer to whether a possible biological bomb involvement in South Africa explains what is happening needs a paradigm shift in one's thinking — prepare to think the unthinkable, and believe the unbelievable. Look at the bare facts: On my African tour researching AIDS 3-14 20-22, I did not include South Africa because there were no cases among the black population, but I did communicate with Professor J Metz of the South African Institute of Medical Research in Pretoria who sent me some information on VIGS (AIDS in Afrikaans) confirming that AIDS began in the white population. Within 15 years the situation in the black community has become quite unbelievable. "With an estimated five million people infected" write Fassin and Schneider, "South Africa has the highest number of people with HIV in the world."1 Experts maintain this is all from sex. Is it not cruel to suggest that black majority rule has suddenly produced a sexual revolution? When Gisselquist and colleagues point out that some HIV Positive children in sub-Saharan Africa have "HIV Negative mothers"23 and that "more research is warranted to clarify risks for HIV transmission"23 they were promptly slapped down by those who subscribed to the view of the African's alleged sexual prowess. "Don't emphasize the dirty needle contribution to AIDS", they say, "it will only make them continue their promiscuity". But North Africans are no less promiscuous than sub-Saharan Africans, yet they only have a fraction of the continent's AIDS problem12 14.

BBC's Disturbing Revelations

"Science In Action BBC World Service Sunday 18 October 1987 GMT 09.15 to 09.45"24 Stephen Hedges, regarding a hospital ward where 30% of the patients were HIV-Positive: "THE RAVAGES OF AIDS IN AFRICA. Film-maker Scot Finch reveals the frightening results of a fact-finding mission he undertook with a team of doctors and scientists to assess the spread of AIDS in Central Africa: 'We were in one hospital where the doctor has to use five needles for twenty patients; three syringes, and use the same syringes, the same needles on the AIDS and non-AIDS patients alike. Now this is absolutely horrifying' (Scott Finch was talking to Stephen Hedges in Science In Action, coming to you from London in the World Service of the BBC)". In the same report Scott Finch said: "One very eminent doctor said, 'if we in the Congo don't change our sexual habits, the Congo could be wiped off the map.'"24 It was like demonstrating the connection in the UK between infected blood and AIDS in haemophiliacs, only to prompt a campaign: "If you don't change your sexual habits, and wear condoms, you haemophiliacs will all be wiped out".

The Times recently ran the headline "Botched vaccinations blamed for AIDS in Africa"25 to highlight the report of Dr Gisselquist and colleagues23. An important aspect of Fassin and Schneider's article1 is that when the multifactorial causes of the AIDS epidemic are ignored, suspicions are immediately raised in the African mind.

Suspicion? African Paranoia? Or both?

When South Africans become alarmed about the fact that "some white leaders…even publicly rejoiced over the possible elimination of black people by disease, as one member of parliament did in 1992"1 their suspicions of racist plots are always dismissed as "Conspiracy Theories". We Africans should not be preoccupied with conspiracy theories, but when the President of the USA apologizes for Conspiracy Facts26, then it was time we began to look at all the channels of infection, for example "attempting to spread HIV through a network of infected prostitutes"1. On May 16, 1997 President Clinton apologized to the eight remaining survivors of the Tuskegee Syphilis Experiment: "The United States government did something that was wrong, deeply, profoundly, morally wrong. It was outrage to our commitment to integrity and equality for all our citizens. It was clearly racist."26 In 1932, a group of scientists secretly selected 400 black people from Tuskegee, Alabama, who were never told they had syphilis. They were watched and monitored for 40 years. Even when Penicillin became available they were denied treatment. The experiment was stopped only when the American public was alerted to it, and became outraged, but by then many of the people had died from "syphilis-related heart conditions."27

Should South Africans who are deeply suspicious about the phenomenal increase of HIV/AIDS among the blacks, and who kept asking: "What on earth is happening?" be branded paranoid? The Financial Times28 had a photograph of "Children from Zevenfontein, where 85 percent of the community are HIV- Positive."28 Although it is impossible for sex alone to do this, we hear reputable broadcasters continue to say: "Rape incidence in South Africa is the highest in the world! Even babies less than one year old are raped regularly because the HIV-Positive African thinks having sex with a virgin gets rid of the infection. The younger the person raped, the better!" How many rapes per night and day would turn the Zevenfontein community to be 85% HIV-Positive? Or produce "the extremely rapid growth in HIV seroprevalence, for example from 0.7% in pregnant women in 1990 to 24.5% in 2000, reaching 36.2% in KwaZulu Natal"1? When Fassin and Schneider report that "in the year 2000 AIDS accounted for 25% of all deaths, and mortality was 3.5% times higher than in 1985 among 25-29 year old women and two times higher among 30-39 year men"1, is that not 'a cry for help' and a 'wake up call'?

The British Medical Journal cover photograph and anti-retroviral drugs

The BMJ's stunning cover photograph29 showed scores of youth wearing "H.I.V. POSITIVE" T-shirts, who appeared to be rejoicing, as if wearing 'Badges of Honour' but really were captioned: "South Africans protest for anti-retroviral drugs"29. The assumption is that all these youth, and the pregnant women, became sero-positive through sex, but from what we have seen above23 24, is it right to make that assumption? And now that HIV vaccines are being heralded as the only answer to Africa's AIDS problem, should we not listen to what one Ghanaian physician said? Commenting on the "let's wait for a vaccine" prescription for AIDS he said: "Look here, for a vaccine to be worth its name, it must produce antibodies. Would you surrender your seronegative status for a seropositive one?"30 If a pregnant South African lady was persuaded to be vaccinated, and she changed from being HIV-Negative to HIV-Positive, would she not also join this crowd demanding that President Thabo Mbeki sign a cheque for anti- retroviral drugs even though the government blocked their use, "citing the drugs' side effects"1?

Widespread grumbling and non-compliance with the "wear condoms" message

Everywhere in sub-Saharan Africa this intense suspicion has turned to "African Paranoia"13:

Nairobi's Kikuyu Province: "We prefer the Missionary nurses to vaccinate our children. We do not trust the other vaccines."

Maeduiguri University, Nigeria: "We fear the donated sanitary towels may contain HIV because they produce intense itching in our private parts".

Lagos: "Vitamins are not vitamins anymore. They are full of contraceptives".

Abuja: "They planted in our leading International Hotel, a very beautiful prostitute from Mali to infect us".

Kampala: "The professor successfully treating HIV/AIDS with herbal immune boosters has been struck off the medical register. One attempt has been made on his life."31

A Ghanaian city: "The haematology kit we got from abroad was dangerous. HIV- Positive blood showed 'Negative', and HIV-Negative became 'Positive' when we checked with our tested controls."

Doctor in Tema, Ghana: "I am seeing more and more young adults with azospermia. Imported food with spermicides? Is that what the Genetically Modified food is meant to do? No wonder the Zambians turned down the GM food offer."

Ghanaian Midwife, Accra: "The way Vitamin A is being pushed everywhere, radio, TV, newspapers, makes us very suspicious. Surely we have palm oil with plenty of Vitamin A? Why don't we push that instead?"

Volta Region, Ghana: "The condoms have lubricant with HIV, and holes specially made to transmit the virus, but block sperm. Preventing pregnancy, and causing AIDS as well?"

Government doctor in East African country: "Instructions came that we should no longer test blood for HIV before surgery, because blood transfusion is not a significant cause of AIDS transmission in sub-Saharan Africa32".

Mother of children in International School in sub-Saharan Africa: "The children brought a letter announcing vaccination against meningitis. It said children from other countries should go to their respective embassies for their jabs. Isn't our vaccine good enough for the others?"

Businessman with children in International School: "My son born abroad received a letter telling him he needed to go to the embassy for any vaccinations he required in future, while my other son will be vaccinated at school. Why?"

Kumasi, Ghana: "The herbalist, Nana Drobo, who treated many people including French men with AIDS, was assassinated on his farm33. Anybody using African traditional herbs for AIDS treatment is threatened, as happened in Kenya."

Douala, Cameroon: "The British-trained professor who has found a revolutionary way of treating AIDS, and is sending people back to their jobs, has been rubbished internationally".

Abuja, Nigeria: "The Specialist treating HIV/AIDS his own way has been threatened with closure, even when he has successfully treated 30 Air Force personnel".

Nairobi: "Why should they come to a church and get our children out of Sunday School to be vaccinated? Would they do that in England?"

Influential government official in West Africa: "What scares me is that I do not know how to tell the good white man from the bad one. I sent one packing last month only to find later that he was the good one."

Accra: PhD Lecturer: "The 'You are all at risk' message with a finger pointing directly at one from the poster on the Brewery Road, near the Daily Graphic, always irritates me. How is a happily married man also at risk of HIV/AIDS? Unless, of course, they are spreading the thing quietly through needles as well."

Kampala: "Police were sent to beat us up when we refused our children vaccination. My first child has not yet recovered from last year's immunization. One friend of mine's child turned HIV-Positive after vaccination."

Lagos: [Secretary to the Cabinet, Chief Samuel Olu Falae]: "Don't these scientists know that AIDS has less to do with green monkeys than blue movies?"22

Accra: [Scripture Union Chief Executive, Mr Jude Hama]: "NGO's come offering us money to distribute condoms to students. Our converts are taught not to have sex outside marriage. Do these NGO's want the children to have a taste for sex in their teens? Sadly, our own Medical Officers do not support us in this."

And so on, and so forth. Even WHO and UN pronouncements are received coolly. The statement last year by a UN Senior Official that Heads of State should be "kicked out"34 if they did not toe the official line for AIDS control brought the paranoid retort: "They have been in charge of the AIDS Programme for the past 16 years, and all we see is calamity after calamity, while they blame it all on sex. Now we hear: 'Obey our AIDS population control plan, and you stay in power. Disobey, and you go'. Soon they are going to ask us to submit to HIV vaccination that will turn us all HIV-Positive. The Head of State that does not enforce this, will be 'kicked out?'"34

These interpretations of official intentions proliferate. Even the women in the sex trade whom I interviewed around the continent were full of such conspiracy theories. They are convinced someone wants to "wipe out Africa", even while they continue with their "quantitative and qualitative abnormal sex"6 7 12 to produce a "preponderance of females with AIDS."35

Everywhere I visited, I found suspicion, fear, and paranoia that seemed to undermine genuine immunization programmes.

The Population Dimension

Paranoid Africans think the white man's plan for them is "Selective Population Control." The Times' leading article the same day Fassin and Schneider's paper was published says: "The world's population in 2050 is now expected by the UN Population Division to be 8.9 billion. That is 400 million fewer than expected as recently as 2000 and a billion below the figure predicted a decade back." It goes on "By 2050, the death toll from AIDS is expected to have climbed to 278 million, and 178 million fewer babies will have been born because the impact of the epidemic on women of child-bearing age." The Times proceeds (chillingly) "Despite high fertility rates, Southern Africa's population will actually shrink."36

Is any of this partly (or wholly) due to what The Lancet called Biological warfare's "public health in reverse"19? Is an iatrogenic population depletion going on faster around the Tropic of Capricorn than anywhere else in the world?

Denial of reality & Denial of the unacceptable versus Denial of wrong doing

'AIDS Dissidents' have a broad spectrum ranging from those who deny that HIV exists at all, across to those who admit that something peculiar was happening, but that it should not be called HIV-AIDS but was a manifestation of old diseases, and on to those labelled 'Dissidents' simply because they queried the "official line" regarding anti-retroviral management. There are also some who, because they have tested 'Positive' in one laboratory (say in Africa) but 'Negative' several times in Europe, insist the whole thing is a hoax to lure them to take immune deprecating drugs that lead to AIDS and death. Joan Shenton37 lists scores of diseases that will test 'HIV-Positive' with some test kits.

Yet some others deny 'HIV' is infectious because they had refused to wear condoms when the wife was HIV-Positive, and they had remained HIV- Negative for ten years or more — the so-called 'Discordant Couples'. They ask: "If the thing is infectious, why am I not infected, and why are there thousands of British HIV-Negative widows of haemophiliacs who had died from AIDS?" Then, as Fassin and Schneider state, there are yet others who deny HIV/AIDS — "even a state leader"1 — because they find it difficult "to comprehend the magnitude of the epidemic" and its consequences "such as the loss of 20 years of life expectancy within 2 decades."1 In my opinion, such denial was very dangerous because while promiscuity continued to be blamed, transmission by needles could go on undetected.

There is also the denial of wrong doing. "How could anybody do a thing like that — deliberately (or accidentally) infect Africans with HIV? The thing is unthinkable", they conclude, but because of apartheid hindsight, "what could be seen elsewhere as unfounded suspicion was in South Africa plain reality, historically attested."1 When that meticulous epidemiological researcher-detective, Ed Hooper, described the role of accidental contamination of polio vaccine with HIV in the AIDS epidemic38 there were frenetic denials of wrong doing. Meanwhile, African Ministers of Health who kept denying that there was an AIDS epidemic, would never be concerned about ever asking the question: "Has the accidental contamination that Hooper revealed, stopped happening?"

Misinformation and Disinformation

'Misinformation' with 'Disinformation' about the AIDS epidemic on the African continent was rife9, and that was what made me decide to search out exactly what was happening in the sub-Saharan region. 'Disinformation is deliberate misinformation' 9 13. To say that eating green monkeys produced AIDS was misinformation, but for a professor of Immunology to publish that Africans could have developed HIV/AIDS through injecting monkey blood for sexual arousal39 was disinformation. To broadcast that Central Africans and some homosexuals with AIDS had inherited something found in their blood called group specific component Gc1f which predisposed them to AIDS40 was misinformation rather than disinformation because after it was pointed out to the authors that their facts were wrong 5 13 they apologized unreservedly and said there had been a laboratory fault 41.

For accredited authorities of 'AIDS and the Third World' to publish two maps showing Ghana striped with AIDS while neighbouring Ivory Coast (which had international prostitution legalized as an industry) was recorded as being entirely free of the disease42 was disinformation. A virtual ban on talk about the sex trade as a chief cause of spread of AIDS was officially maintained to avoid "sex discrimination", which raised the kind of suspicions circulating in South Africa where it was feared attempts were made "to spread HIV through a network of infected prostitutes"1.

Sometimes the misinformation/disinformation debased the African, as when it was announced that some American scientists had discovered monkey retrovirus antibodies in the blood of Senegalese prostitutes. When the findings were challenged the authors admitted that they had made a mistake, and that there was contamination in their laboratory of human blood and monkey blood43. To redeem the reputation of their great university, a senior professor wrote an editorial about the episode which she called: "A case of mistaken non-identity"44. What surprises us Africans is that after the original misinformation had made world news, and the scientists later confessed error, not one newspaper or radio/TV channel went back to correct the facts. The general public therefore continued to believe that the African did, in fact, inject monkey blood into his thighs for sexual arousal, that Africans did share some genes with AIDS afflicted homosexuals, and that Africans harboured in their blood antibodies of monkey retroviruses. There seemed to be not a single international journalist worth his salt who would stand up for the African. Could all this be a manifestation of "racism"? And, in any case, why should people be mixing monkey blood with human blood in the same laboratory as the two professors did in Boston43?

Racism and Retroracism

Fassin and Schneider observed that racism had led to "suspicion in South Africa of science and orthodoxy — a suspicion that is widespread and not confined to the president and his advisers."1 Certain scientists, in my opinion, genuinely believe that 'blacks' are inferior to 'whites'. With little knowledge of the black person's previous history and real potential, these prejudiced 'whites' have stretched Darwinian Evolutionism to absurd limits. The full title of Charles Darwin's treatise45 is:

"THE ORIGIN OF SPECIES BY MEANS OF NATURAL SELECTION OR THE PRESERVATION OF FAVOURED RACES IN THE STRUGGLE FOR LIFE"

As I once I stated46: "The term 'race' is a misnomer. There is but one human race, with different peoples. James Bowman and Robert Murray47 should be applauded for the title of their excellent book, Genetic Variation and Disorders in Peoples of African Origin. Others would have used 'the African Race' in the title."46 Sequencing the human genome confirmed recently the fact of just one human race. Darwin's 'favoured races' would want to survive at the expense of the 'unfavoured races'.

Looking at some unflattering pictures of half naked Africans in glossy magazine advertisements, for example, Chief Obijol and his "series of clicking sounds"48, racists would like to think that the African was inferior and slow to evolve. They would be terribly mistaken because the African, in his present sorry plight, is not a case of delayed evolution; he is a classic example of accelerated degeneration. There were Black Pharaohs in ancient Egypt, and before Europe was Europe, and while the Caesars were teaching the British Isles to read and write, the Ethiopian Chancellor of the Exchequer of Queen Candace, was reading The Prophet Isaiah fluently49.

There are South African whites who have vowed never to be ruled by a black president, and are like the ones Fassin and Schneider describe as rejoicing in parliament "over the possible elimination of black people by disease"1. These racists require a mental paradigm shift about the black man. The process can be very painful, as was manifested in the case I once described46 of a British university Reader who confessed his racism to a Ghanaian pre-Clinical medical student he had misled in order to deprive him of a First Class Honours Degree. He "could not bear to think that a black African would learn English as a second language, study in the language, and beat all comers."46 But after he was deprived of what he deserved, that African went on to emerge in the Finals with Honours and Distinctions, to top the whole university of more than 200 newly qualified doctors, and was rewarded by a non-racist Lord Max Rosenheim FRS PRCP, who picked him to be his House Physician. The Ghanaian went on to achieve exploits. I know many white South Africans who are as colour blind as Lord Rosenheim was, and who will not rejoice as their parliamentarian did, because the African population was being decimated.

RETRORACISM: I met this phenomenon in several countries I visited in sub-Saharan Africa. "'Retroracism'" I once wrote, "is a term I coined to mean reverse racism. A retroracist is usually a black man who is consumed with hatred for the white man."13[page 196] As white racists are best dealt with by white people, so retroracists are most efficiently controlled by fellow Africans. Black South Africans (and all the non-white population), have an obligation to help those among themselves who are retroracists because genuine, non-racist, white people feel intimidated by retroracists, and this can prevent South Africa from dealing with the AIDS epidemic properly and collectively without mistrust raising its ugly head on either side.

Meaningful Interventions

If one does not accept the multi-faceted nature of the HIV/AIDS problem1 plus the role of soiled needles23 24, then even the most elaborate interventions will miss the mark. If the effects of behaviour change and condom use "were not translated into any measurable reduction in HIV-1 incidence"50, then perhaps non-sexual parameters of HIV transmission needed looking at seriously. "Evaluation of promising interventions" as has recently been pointed out, "is essential to the success of HIV prevention"51. To assume that sex is the overwhelming cause of the havoc in South Africa will leave unexplained the HIV-Positive virgins whose mothers are HIV-Negative.23 Meaningful interventions at the grass-roots using appropriate technology in Kenya have been emphasized by Professor Thairu52, and domiciliary management of AIDS in Ghana by Professor Quartey and team53, without resort to anti-retroviral drugs, has been shown to be cost effective. They proved the value of a decentralized approach to the epidemic. For instance, in my Manya Krobo tribe in Ghana where we have clearly worked out the local clinical epidemiology to perfection4 13, we know that only targeting the main local cause of the epidemic can be of any use. Yet, the centralized National AIDS prevention campaign appears not to be tackling root causes, and the problem just gets worse and worse despite the "wear condoms" slogans recommended from abroad by those who supply funds to the tribe.

We need the kind of comprehensive approach which looks at everything3 4 12 20. Girls trading in sex within the tribe got much less than one Dollar per client, but if they went across Ghana's boundaries to nearby Ivory Coast, or Togo, or Burkina Faso (all ex-French colonies) one coital act fetched them 25 Dollars. Not once have I heard the catastrophic role of international prostitution mentioned as a factor in the spread of HIV/AIDS. To distribute condoms to these girls in a survey to see the effect on HIV spread is to betray ignorance of what happens at the grass roots. These girls are not in a position to give 'wear condom' instructions to their clients? Even when 'abnormal sex'6 which they themselves confess is "very harmful"3 4 13 is demanded of them they acquiesce but, as one girl informed me in Burundi "mais je le demande une grande somme d'argent14. A meaningful intervention against HIV/AIDS for such a girl in Hotel Source du Nil in Bujumbura was not a generous supply of condoms, but a sewing machine. "If I get a sewing machine, Monsieur le Docteur, or a type writer, or both, I shall stop this dirty job"3 13[page 143], she told me in tears. By the time I could send her the sewing machine from England, Anna-Marie was dead.

If South Africans do not quantify each single contributing cause of their epidemic, identifying whether there is an iatrogenic dimension or not, then little progress will be made. If in any country, interventions meant to help, are rather producing a deteriorating situation, then remember Tuskegee, and hidden agenda cannot be ruled out. The so-called interventions must somehow be contributing to the deteriorating situation. Unthinkable, yes, but one requires a brain paradigm shift to make it thinkable. The same NGO can contain foreign helpers where the left hand does not know what the right hand is doing. While the left is working for "The planet in 2050", and must needs rejoice "over the possible elimination of black people by disease"1 the right hand is relieving pain and suffering of the African here and now.

I did ward rounds with a remarkable 'white lady doctor', as she was called in Uganda. "Dr Miriam Duggan, the obstetrician-gynaecologist medical superintendent of the large St Francis Hospital, Nsambya, in Kampala", I revealed, "was saddened by the way that external research agencies lost interest whenever she mentioned the need for strengthening her clinical epidemiological research base to enable her go round the villages to follow up and treat patients with AIDS who had been discharged, and to measure longevity"4. I am delighted to learn that Sister Duggan, who is a practising Christian, has managed to remain in Africa, toiling at the grass roots. Many other good 'white doctors' who also took me on ward rounds in sub-Saharan Africa, have left the continent. Some of them did so suddenly. I often wondered whether they saw what was happening, raised objections, and were asked to leave by the NGO's that sent them there. But no one can force godly missionaries to leave. How successful an NGO is in controlling disease, suffering, and death of the African depends not on the "organization" but on the philosophy of the brains behind it. Godly missionaries have one philosophy: they slave away to relieve suffering in 2003 AD. Others prefer to talk about Africa's population in 2050 AD.

Even 'Malaria Control' in Africa (preventing the death of 3 million children every year) would also not succeed if those in charge of the programme were some population-control-by-hook-or-by-crook experts, leading me once to remark: "But would averting a malaria disaster not upset the population control lobby?"54. Population containment achieved ethically to enable Africans have enough food to eat and maintain a reasonable standard of living is a good thing, as Professor Fred Sai has always maintained55 56, but population control by hook or by crook, ie through man-made epidemics19 is very wrong — to use President Clinton's phrase.26

Action, please, before it is even more too late

Alas, it is all too late because no scientist was prepared to heed Lancet's warning 35 years ago, and defuse the Biological Bomb. There are more explosions to come, "lying at the heart of the cellular nucleus, ticking us to destruction."19 The experiments for 'hidden agents' have not stopped. Scientists are still doing what they like with the human genome, entering a realm of great potential for evil. Lake Superior State University invited some 21 of us to produce a Symposium on the "Human Genome Diversity Project"57 and published it in one volume with another Symposium titled "Is Humanity destined to self-destruct?"57

We were asked to comment on David Resnik's earlier contribution on the ethical aspects of the HGDP58. Professors Alper and Beckwith discussed the potential for racism in the project59, and Professor Frank Dukepoo, "a full blooded Hopi/Laguna American Indian"60 mentioned how "the potential for 'scientific racism' is high and potentially explosive"60. Dukepoo underlined the same fear Lancet expressed 35 years ago: "If we race forward with biomedical/biogenetic research and ignore ethical, legal, social, and other issues, we will suffer the consequences"60. Scientists are capable now of fashioning and modifying genes to produce specific 'hidden agents' for different ethnic groups. So when we hear that a new HIV vaccine is bad for whites, but good for Africans and Asians61 what is a suspicious and paranoid African supposed to think? Dukepoo continues: "When recombinant DNA technology became a reality, eleven of the leading scientists in the new field of molecular biology published an open letter on July 26, 1974, asking their colleagues to initiate a self-imposed moratorium on conducting high-risk DNA recombinant experiments (Rifkin 1998).62 In the end, the moratorium was lifted as moral responsibility was trampled by financial interests. Will history repeat itself?"60

How much of that work could have been going on in South Africa which allowed the country to have "the highest number of people with HIV in the world"1? When Joseph Chamie, director of UNDP, was quoted in Lancet last month as saying "HIV/AIDS is a disease of mass destruction"63 what else do we want to hear before we take some kind of action? And, looking around, The Third World ("the unfavoured races") is where this destruction is greatest. Richard and Rosalind Chirimuuta64 have always maintained that AIDS is linked to racism. Close to tears, I once pleaded: "Finally if, God forbid, it is proven that this whole AIDS mess began in a laboratory with scientists tinkering with genes of baboons and humans, then the most powerful nations on earth should call a conference and halt such research forthwith."13[page 160] Nobody heard me.

Conclusion

What is happening in South Africa is more than meets the eye. With scientists confessing to what they had been doing in molecular biology laboratories during the apartheid regime1, it is difficult to escape the conclusion that the hyper-escalation of the HIV/AIDS problem from zero incidence in the black population less than 20 years ago, to being the world's leading problem is not a natural phenomenon. Oxford's Professor George Fraser has translated from the German edition Benno Muller-Hill's "Murderous Science: Elimination by Scientific Selection of Jews, Gypsies, and Others, Germany 1933-1945."65 The evil of Nazism could be going on surreptitiously right now to get rid of the "less favoured races". World Democracies, please help! Sometimes we are told: "These things are matters of National Security, and cannot be probed". Can't they?

Epidemiology of HIV/AIDS varies from place to place3 4 13 so if we get the methods of propagation wrong in a particular place, we shall get our "interventions" wrong as well, and the situation will get worse and worse. We have just been told: "A group convened by the World Health Organization has reiterated its view that unsafe sex is the principal route by which HIV spreads in Africa."66 The account went on: "The group rejected the idea put forward recently in an AIDS journal that the careless use of injections was a major factor in spreading AIDS". Then comes the usual expert opinion: "Such suggestions 'are not supported by the vast majority of evidence', the group said, adding that unsafe sexual habits continue to be responsible for the majority of infections. But it did acknowledge the dangers of dirty needles"66. But this statement begs the question. How can any expert explain scientifically how South Africa had negligible HIV/AIDS incidence just before apartheid was overthrown, but has since climbed to overtake the whole world to be Number One? Would the group assembled by the WHO explain in simple epidemiological terms how it was possible for the Zevenfontein community in South Africa to be 85% sero-Positive? Could this WHO group exclude Murderous Science65? If, as these experts claim, "careless use of injections"66 cannot be blamed for much of what is happening in South Africa and the rest of sub-Saharan Africa, what about the "careful use" of injections as happened in Nazi Germany65? Have we proven beyond all reasonable doubt that there are no present-day scientists with Nazi proclivities? Even when some such have confessed in South Africa1? Fassin and Schneider's article1 would be utterly useless, if it did not wake us up to do something about this catastrophe. Paranoid Africans need urgently to be freed from their fear.

Secretary General of the UN, Mr Kofi Annan, finished his Foreword67 to a recent book co-authored by a German and a Ghanaian68 thus: "While not everyone will agree with the specific strategies proposed by the authors, I believe that this book will stimulate constructive debate which will bring us closer to the objective of worldwide HIV/AIDS prevention and control."67 The book, with a 'Question & Answer Format' has provided answers to scores of questions, the very first of which is:

"Are current concepts for combating HIV/AIDS in developing countries adequate?" and the answer they give in bold letters is this:

"Absolutely not! There is an urgent need to change the paradigms of thought and action"68.

If we do not urgently "change the paradigms of thought"68 and look beyond sex and the African's alleged hyper-sexuality, we shall be unable to change our "action"68, and we shall plunge the continent into deeper and deeper catastrophe, with the continuing victim-blaming repertoire produced by the world media — if these Africans do not change their sexual habits, they will all be wiped out, and "Africa left to the lions"69.

If the main problem, as I see it, is that of 'Human Immune Deficiency DNA' genetically engineered and purpose-built to wreak havoc on the immune system, then the approach, therapeutically, must be emphasis on immune boosters. Such immune enhancing products are available among some African traditional healers the success of at least one of whom was verified and reported to the WHO in Geneva21 70. If the ultimate aim of AIDS patient- management is to help ameliorate the circumstances of ailing Africans and, as Kofi Annan said, "bring us closer to the objective of worldwide HIV/AIDS prevention and control"67, then anything that enables sufferers to improve so that they can go back to their farms should be encouraged. Control of the epidemic needs to be left in the hands of those who want to relieve suffering, and not of those who secretly or openly rejoice1 when they hear the horrendous figures of the dead being broadcast weekly by the world's media.

Please, let the reaction of readers of this article not be: "But O, we have heard it all before. There is nothing new in it. These Conspiracy Theories will go on and on. Let these Africans just stop being promiscuous, and the problem will be solved. The majority of the available evidence shows that all this is total nonsense." And so on. We shall otherwise be stuck in the AIDS calamity hole.

I am praying hard for a 21st Century William (or Williama) Wilberforce who will be bold enough to help save the African from this predicament. My William Wilberforces would need the staunch support of the three British Editors who had the integrity to publish statements that called a spade a spade: Lancet ["The Biological Bomb19…public health in reverse19…HIV/AIDS is a disease of mass destruction"63], Nature ["Artificial HIV?"17], BMJ ["Issues of race hinder public health29…and they even publicly rejoiced over the possible elimination of black people by the disease, as one member of parliament did in 1992"1]. I appeal to any godly person reading this communication: Please, pray that the conscience of even the most ungodly and Nazi-like scientists involved in such evil research and programmes for "elimination by scientific selection"65 will be smitten, to make them confess, and repent. Things are going to be much, much, worse. If such research continues, then more viruses will be announced from time to time as just having "emerged" [HIDDNA-1, HIDDNA-2, HIDDNA-3, etc]. And Central Africa is always a convenient place whence they do emerge. There could be as many HIDDNA viruses as there were laboratories, capable of fashioning the 'hidden agents' to match different ethnic groups globally. Things are unlikely to get better until the required population reduction is reached after 2010, according to the "projections". Meanwhile, for little symptomatic mercies, perhaps the last paragraph of my Editorial to The AIDS Letter of The Royal Society of Medicine might help some people re-examine their 'Intervention Programmes':

"Finally, the kind of research that will help Africans curtail AIDS does not have to be the vaccine-oriented research of the developed countries. Public health methods and clinical epidemiology are the best tools. Ultimately, modification of sexual behaviour through secular and spiritual education, backed by provision of light industries to generate the kind of foreign exchange in search of which the girls go into prostitution, is by far the best approach to AIDS prevention in Africa. I know that in addition to the multitude of Africans living abroad, there are many non-African friends of the continent who, when told what is happening, are prepared to donate their help at the grass roots level on the lines mentioned above."12

F I D Konotey-Ahulu MD(Lond) DSc(UCC) FRCP(Lond) DTMH(L'pool) FWACP Fellow of The Ghana Academy of Arts & Sciences and Fellow of The Third World Academy of Sciences Kwegyir Aggrey Distinguished Professor of Human Genetics Faculty of Science, University of Cape Coast, Ghana, and Consultant Physician, Tropical Medicine Dept., Cromwell Hospital, London SW5 0TU [E-mail: felix@konotey-ahulu.com]

Acknowledgements: I thank my wife Rosemary for agreeing that I could borrow money to travel to African countries to study AIDS at the grass roots. I am grateful to all the people who agreed to see me including Ministers of Health, Directors of Medical Services, and Doctors who took me on ward rounds. I also thank Ghana's Professor John Kwashie Quartey and his Domiciliary Management Team who tackled AIDS in my tribe, and Kenya's Professor Kihumbu Thairu who taught me the importance of using appropriate and affordable means for tackling the problem. I also thank no less than 118 ladies of the sex trade who agreed to talk to me privately even while on duty in many of the sub-Saharan African countries. I am grateful to the Editors of the medical journals, especially the British ones, who agreed to publish almost anything I sent to them. Finally, I thank my GOD, who delivered me from a terrible accident while traveling by car from Kigali to Butare in Rwanda, and who was able to make me dodge coups from one country to another.

Funding: None

Competing Interests: Presently in search of Funds (1). To help reduce the burden of Sickle Cell Disease in the next generation in Ghana, and in Ghanaians in the UK and USA, with Genetic Counselling and Ethical Family Planning: www.sicklecell.md and (2). To reduce HIV/AIDS incidence in my tribe by helping the Paramount Chief, King Nene Sakitey II tackle the roots of the epidemic in Manya Krobo in south-east Ghana, and teach the Krobos to read Literature in their Mother Tongue: www.aidsinafrica.co.uk

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6 Konotey-Ahulu FID. Origin and transmission of AIDS. Journal of Royal Society of Medicine 1987; 80: 720.

7 Konotey-Ahulu FID. Extensive palatal echymosis from felatio — a note of caution with AIDS at large. British Journal of Sexual Medicine 1987; 14: 286-87.

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11 Konotey-Ahulu FID. HIV-2 in West Africa. Lancet 1989; 1: 553.

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14 Konotey-Ahulu FID. HIV antibody positive sub-Saharan African patients in UK. Lancet 1990; 335: 46-47.

15 Duesberg PH, Ellison BJ. Is the AIDS virus a Science Fiction? Immunosuppressive behaviour, not HIV, may be the cause of AIDS. Policy Review (The Heritage Foundation). Summer 1990, Washington DC.

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20 Konotey-Ahulu FID. Slowing HIV contagion among Africans. International Journal of Sexually Transmitted Disease & AIDS 1991; 2:139

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22 Konotey-Ahulu FID. African AIDS through African eyes (Guest Editorial). AIDS Analysis Africa 1991; no 1 p 11, March/April.

23 Gisselquist D, Rothenberg R, Potterat J, Drucker E. HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. Int J STD & AIDS 2002 Oct; 13:657-66.

24 Science In Action. The ravages of AIDS in Africa. BBC World Service 1987 18 October, GMT 09.15 to 09.45.

25 Hawkes N, Dynes M. Botched vaccinations blamed for AIDS in Africa. Times; Thursday February 20 2003, p 3, London.

26 Clinton President W J. Apology on behalf of the American government to survivors of the Tuskegee Syphilis Experiment victims. Worldwide radio & Telvision. May 16 1997.

27 Jones JH. Bad Blood: The Tuskegee Syphilis Experiment. New York: Free Press, 1981.

28 Financial Times. AIDS in South Africa. Friday, 20 September 2002, page 14.

29 BMJ. Understanding AIDS in South Africa: Issues of race hinder public health. 1 March 2003; 326, outer cover.

30 Konotey-Ahulu FID. AIDS in Africa. Lancet 2002; 360: 1424

31 Njuma Times. Ssali escapes panga attack. January 27 1998, p2.

32 Konotey-Ahulu FID. Black people's red faces and AIDS prevention. Lancet 2000; 355: 1559

33 Robinson M. The last miracle of Nana Drobo. The African Chief and his Miracle Cure for AIDS. The City Magazine, Tokyo; Dec 1992, pp24-31.

34 BBC Radio 4. The World This Weekend: AIDS Conference, Spain, July 7 2002 - 1 pm .

35 Neequaye AR, Neequaye J, Mingle JA, Ofori-Adjei D. Preponderance of females with AIDS in Ghana. Lancet 1986; 2: 978.

36 Times (Editorial). The World in 2050. Gains and strains as population growth slows. Saturday March 1, 2003 p 29, London.

37 Shenton Joan. Positively False. Exposing the Myths around HIV and AIDS. London I B Taurus. 1998.

38 Hooper Edward. The River. A Journey Back To The Source of HIV and AIDS. London. Allen Lane. Penguin Press. 1999.

39 Karpas Abraham. Origin of the AIDS virus explained? New Scientist. July 16 1987.

40 Eales L-J, Nye KE, Parkin JM, Weber JN, Forster SM, Harris JRW, Pinching AJ.Association of different allelic forms of group specific component with susceptibility to and clinical manifestation of human immunodeficiency virus infection. Lancet 1987; 1: 999-1002. 41 Eales L-J, Nye E, Pinching AJ. Group-specific component and AIDS: Erroneous Data. Lancet 1988; 1: 936.

42 PANOS. AIDS and the Third World. The Panos Institute. London 1986.

43 Essex M, Kanki P. Comparison of simian immunodeficiency virus isolates. Nature 1998; 331: 621-22.

44 Mulder C. A case of mistaken non-identity. Nature 1988; 331: 562- 63.

45 Darwin Charles. The Origin of Species By Natural Selection Or The Preservation Of Favoured Races In The Struggle For Life. London 1859. Reprinted, Penguin Books 1968.

46 Konotey-Ahulu FID. The Human Genome Diversity Project: Cogitations of An African Native. Politics and the Life Sciences (PLS) 1999; Volume 18: No 2, 317-322

47 Bowman J, Murray RF. Genetic Variation and Disorders in Peoples of African Origin. Baltimore/London: The Johns Hopkins University Press.

48 TIME Magazine. How well do you share? Ricoh Image Communication Advert featuring Aficio solutions. (Inside Cover) December 16, 2002.

49 ACTS of The Apostles. Conversion of Ethiopian Eunuch through Apostle Philip. Chapter 8 verses 26-40.

50 Kamali A, Quigley M, Nakiyingi J, Kinsman J, Kengeya-Kayondo J, Gopal R, Ojwiya A, Hughes P, Carpenter LM, Whitworth J. Syndromic management of sexually -transmitted infections and behaviour change interventions on transmission of HIV- 1 in rural Uganda: a community randomized trial. Lancet 2003; 361: 645-52.

51 Stephenson Judith M, Cowan Frances M. Evaluating interventions for HIV prevention in Africa. Lancet 2003; 361: 633-634.

52 Thairu K. Appropriate Technologies for AIDS Management in Africa, Editor. Kenya Medical Research Institute, Nairobi, 3-7 September 1990. Commonwealth Secretarait, London.

53 Quartey JKM, Konotey-Ahulu FID. The domiciliary management of AIDS in a rural community in Africa. In: Appropriate Technologies for AIDS Management in Africa, 3-7 September 1990. Editor Thairu K. Kenya Medical Research Institute, Nairobi. Commonwealth Secretariat London, pp 42-44.

54 Konotey-Ahulu FID. Averting a malaria disaster. Lancet 1999; 354: 258.

55 Sai FT. Dr Fred Sai speaks out. International Planned Parenthood Federation, London 1994.

56 Sai FT, Chester LA. The role of the World Bank in shaping Third World Population policy. In: Population Policy — Contemporary Issues. Editor G Roberts, New York, Praeger 1990.

57 SYMPOSIA: First Symposium: Is Humanity Destined to Self Destruct? Second Symposium: The Human Genome Diversity Project. Politics and The Life Sciences (PLS) September 1999, Volume 18, Number 2, pages 201-284; 285-340.

58 Resnik DB. The Human Genome Diversity Project: Ethical Problems and Solutions. Politics and the Life Sciences 1999; 18; 15-23

59 Alper JA, Beckwith J. Racism: A central problem for the Human Genome Diversity Project. Politics and the Life Sciences 1999; 18: 285-288.

60 Dukepoo Frank C. More than the Human Genome Diversity Project. Politics and the Life Sciences 1999; 18: 293-297.

61 McCarthy Michael. HIV vaccine fails in phase 3 trial: Sceptics question subset analysis that suggests HIV vaccine could be protective in non-white people. Lancet 2003; 361: 755- 756.

62 Rifkin J. The Biotech Century. New York: Penguin Putnam, 1998.

63 Schlagenhauf Patricia, Ashraf Haroon. HIV/AIDS lowers UN's global population estimates. Lancet 2003; 361: 841 [8 March].

64 Chirimuuta Rchard C, Chirmuuta Rosalind J. AIDS, Africa and Racism. London, Free Association Books, 1987/1989.

65 Müller-Hill Benno. Murderous Science: Elimination by Scientific Selection of Jews, Gypsies, and Others - Germany 1933-1945. [Translated from German by G R Fraser] Oxford. Oxford University Press, 1988.

66 Times (London). Unsafe sex "is main HIV danger". Saturday 15 March 2003, page 8.

67 Annan Kofi. Foreword to HIV/AIDS: Knowledge Protects: New and Specific Approaches To Contain the Spread of HIV in Developing Countries, HH Repke, E S Ayensu. I Strauss Verlag GmbH, Postdam, Germany, 2001.

68 Repke Heinrich H, Ayensu Edward S. HIV/AIDS: Knowledge Protects — New and Specific Approaches to Contain the Spread of HIV in Developing Countries. I Strauss Verlag GmbH, Postdam, Germany, 2001.

69 Veitch Andrew. How do you avoid catching AIDS? The Guardian, November 21, 1986, page 21 [Medical Corresspondent].

70 Konotey-Ahulu FID. Probing anecdotes in traditional African therapeutics. African Journal of Health Sciences 1994;1:53-56

Competing interests:   Competing Interests: Presently in search of Funds (1). To help reduce the burden of Sickle Cell Disease in the next generation in Ghana, and in Ghanaians in the UK and USA, with Genetic Counselling and Ethical Family Planning: www.sicklecell.md and (2). To reduce HIV/AIDS incidence in my tribe by helping the Paramount Chief, King Nene Sakitey II tackle the roots of the epidemic in Manya Krobo in south-east Ghana, and teach the Krobos to read in their Mother Tongue, thus facilitating Health Education: www.aidsinafrica.co.uk


Okay, provide the references 4 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

Send response to journal:
Re: Okay, provide the references

Dear Editor,

Peter Flegg says that, "What I [Flegg] have done is to point out that HIV is more efficiently transmitted in the acute phase of primary infection than it is subsequently. There is plenty of data verifying this, both epidemiologically and biologically, and if [Rasnick] wants references I will be glad to provide these."

Okay, Peter Flegg, please provide the references that prove that HIV is sexually transmitted--efficiently or even inefficiently. If Flegg thinks that the Padian et al. study provided that proof, could he specifically point out where in that paper the evidence for sexual transmission of HIV is to be found?

While you're at it, please provide the references I asked for:

1) What are the names of the individuals who are documented to have shown how HIV causes AIDS?

2) Failing that, what are the names of the people who have shown that HIV even causes AIDS, regardless of mechanism?

Please, just list the first individuals, along with their potentially Nobel prize-wining publications.

David Rasnick

Competing interests:   None declared


Most Experts Suggest 90% of African Adult HIV is from heterosexual transmission, Gisselquist 30% 5 April 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Most Experts Suggest 90% of African Adult HIV is from heterosexual transmission, Gisselquist 30%

I was (perhaps naively) hoping that alternative AIDS arguments on this page might stand up to scrutiny a little better than they have amongst the responses to David Spurgeon's article. Providing links to journal articles which were falsely implicated as supporting revolutionary ideas about AIDS has been met with either silence or a change of topic by those who have posted the misinformation. The pattern is very much continuing here.

Work by David Gisselquist has been cited in support of alternative AIDS arguments. Gisselquist and others have most certainly published work suggesting that iatrogenic mechanisms of HIV transmission have been underestimated. Please explain (as I have asked already) where there is evidence that "According to Gisselquist and his colleagues HIV is not transmitted by 'sex' "(1)

In addition to the links to Gisselquist articles above which entirely disprove such claims, he has recently published an article about Heterosexual transmission of HIV(2):

---
"For more than a decade, most experts have assumed that more than 90% of HIV in African adults results from heterosexual transmission. In this exercise, we show how data from studies of risk factors for HIV can be used to estimate the proportion from sexual transmission, and we present our estimates. Calculating two ways from available data, our two point estimates - we do not estimate confidence intervals - are that 25-29% of HIV incidence in African women and 30-35% in men is attributable to sexual transmission"
---

The fact that 'most experts' claim it is 90%, and that Gisselquist thinks it approximately 30%, leads one to ask why he has been cited to support claims that HIV isn't sexually transmitted?

References:

(1) Papadopulos-Eleopulos. Low rates of heterosexual transmission and the HIV theory of AIDS. BMJ Rapid Response 24 March 2003

(2) Gisselquist D, Potterat JJ. Heterosexual transmission of HIV in Africa: an empiric estimate. Int J STD AIDS. 2003 Mar;14(3):162-73. PMID: 12665438 [Abstract]

Competing interests:   None declared


Heterosexual Intercourse Found to be the Major Mode of HIV Transmission in a Group of Thai Fisherman 7 April 2003
Tony Floyd,
Medical Student
Newcastle University

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Re: Heterosexual Intercourse Found to be the Major Mode of HIV Transmission in a Group of Thai Fisherman

Aside from David Gisselquist being falsely cited in support of alternative AIDS theories, the response entitled "HIV in South Africa"(1) provides another curious example. A 1994 article by Caceres CF and van Griensven was used to support a theory that ONLY anogenital insertive intercourse and oroanal sex are HIV risk factors. A May 2000 article(2) by van Griensven states:

---
"findings indicate a high HIV-1 prevalence among fishermen in the Gulf of Thailand and the Andaman Sea. Risk factor analysis suggests that heterosexual intercourse is the major mode of transmission in this population."
---

Checking references continues to disappoint anyone trying to find substance in alternative AIDS arguments.

Even if, in most populations, unprotected heterosexual sex carries a LOW risk for HIV transmission, surely any risk should continue to be acknowledged and minimised?

References:

(1) Papadopulos-Eleopulos. HIV in South Africa. BMJ Rapid Response 13 March 2003

(2) Entz AT, Ruffolo VP, Chinveschakitvanich V, Soskolne V, van Griensven GJ. HIV-1 prevalence, HIV-1 subtypes and risk factors among fishermen in the Gulf of Thailand and the Andaman Sea. AIDS. 2000 May 26;14(8):1027-34. PMID: 10853985 [Abstract]

Competing interests:   None declared


Sexual transmission of HIV during early infection 10 April 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Sexual transmission of HIV during early infection

David Rasnick requests (4 April) that I "provide the references".

I said I would willingly provide these for the statement I made. He actually quotes it word for word, but I see I need to remind him what I actually said.

"HIV is more efficiently transmitted in the acute phase of infection than subsequently. There is plenty of data verifying this, both epidemiologically and biologically, and if he wants references I will be glad to provide these".

Rasnick (again) seems to think I said something completely different, and now seems to want references for the evidence that HIV causes AIDS or that HIV is sexually transmitted. Rasnick has been given more than enough references concerning these facts in the past, not only during exchanges on fora such as the BMJ's rapid response section, but during his time on Mbeki's Presidential Panel. I will not waste everyone's time trying to flog this particular horse, which expired a very long time ago. Also, if experience is anything to go by, he would only read into the data whatever he wishes to see. I have better things to do with my time than trot out a comprehensive list of references, only to see the material ignored, misquoted or misinterpreted.

However, concerning the evidence on HIV's efficient transmission in the acute stage of infection, here goes:

Firstly the epidemiological data. One if the first papers to look at the contribution of early transmission concluded that chains of transmission grow rapidly, and this helps explain many observed population patterns for HIV infection (1). More direct evidence accrued for this with the finding within the Swiss HIV cohort Study, which included 191 patients with PHI. Through case contact tracing and nucleic acid sequence analysis it was demonstrated that onward transmission to another partner had occurred in 17 of these cases during the time of PHI (2). A detailed analysis of 5 heterosexual couples where transmission occurred clearly demonstrated the dynamics of early HIV transmission (3).

Turning to the biological evidence, there are also data linking higher rates of transmission with high levels of virus, both in plasma and genital secretions. This has been demonstrated in the Rakai group study in Uganda (4), with the conclusion that "The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1". These levels are often extremely high during PHI (5), and some individuals have seminal viral loads that consistently exceed plasma levels and are considered to be highly infectious "hyperexcretors". Pilcher has also modelled transmission and estimates that during the peak viral shedding that is associated with PHI, transmission would be 20-fold higher than that during stable chronic infection. For individuals with peak seminal viral loads of log 8.85, the probability of transmission per act would be 1.0 (i.e. transmission would occur with every single exposure), dropping to 0.03 for individuals with levels of 5.43log, down to 0.0015 for levels of 3.75log (5). Chakraborty has looked at HIV's infectiousness in 86 males and 24 females, and developed a model for calculating the probability of HIV transmission per heterosexual coital act (6). As levels of HIV-RNA rise in semen, probability of transmission increases (seminal level of log5 equating with probability of transmission of 1 per 100 episodes of intercourse).

Overall, there is plenty of evidence. This list is by no means exhaustive, but covers a spread of mutually-validating data. It would be inadvisable to ignore independently-derived evidence which lends support to a theory unless there is valid data which clearly contradict it.

(1) Jacquez JA, Koopman JS, Simon CP, Longini IM Jr. Role of the primary infection in epidemics of HIV infection in gay cohorts. J Acquir Immune Defic Syndr 1994; 7(11):1169-84. (2) Yerly S et al. HIV drug resistance and molecular epidemiology in patients with primary HIV infection. Abstract 754, 8th Conference on Retroviruses and Opportunistic Infections. Chicago 2001. (3) Pilcher CD et al. Sexual transmission during the incubation period of primary HIV infection. JAMA 2001; 286(14): 1713-4. (4) Quinn TC, Wawer MJ, Sewankambo NK, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 342(13):921-9, 2000. (5) Pilcher CD, Shugars DC, Fiscus SA, Miller WC, Menezes P, Giner J, Dean B, Robertson K, Hart CE, Lennox JL, Eron JJ Jr, Hicks CB. HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health. AIDS 2001 May 4;15(7):837-45. (6) Chakraborty H, et al. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model. AIDS 2001: 15(5):621-7.

Competing interests:   None declared


Support for wake up call and need for paradigm shift 11 April 2003
Dr. Charles Ssali,
Director of Mariandina Research
P.O.Box 169 Dartford,Kent DA2

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Re: Support for wake up call and need for paradigm shift

Proffesor Felix Konotey-Ahulu is to be very much congratulated for collecting so much information from the African continent on the AIDS epidemic. I can corroborate the information he gathered from his trip to my home country Uganda. Inspite of, or rather because of, the huge and unprecidented success I had, in the management of AIDS patients using my nutritional supplements, attacks were made on my life. (Konotey Ahulu reference number 31). The success of my treatment judged by the improvement of the quality of life of the majority of the patients who received the mariandina nutritional immune booster was considered too much of a threat by competitors in the field.

On one ocassion when I went to the blood bank situated on Nakasero hill in Kampala,Uganda ,to acquire some blood for my patients, I casually inquired as to whether the blood was routinely screened for HIV. To my utter amazement, I was told by the doctor in charge, that according to their guide lines, the procedure was not considered necessary because blood transfusion was not a significant way of HIV transmission in Africa.

Two years ago, one student in Oxford who had used a popular brand condoms consistently without fail ,subsequently developed HIV/AIDS. In desperation he sued the National Health Service for damages. The National Health Service won the case because the defence lawyer demanded to see a sample of the condoms the student claimed to have been using. On seeing them, the lawyers pointed out that on the label was written: "For Export only."

When asked what he thought was the reason why children of 7-9 years of age in Zambia were , of late, being found HIV positive in growing numbers .An NGO official replied without hesitation: " African children become sexually active from as early as 6-7 years of age."

Corroborating the fears of a Ugandan mother mentionioned in Professor Konotey Ahulu's account about a child becoming HIV positve after vaccination, I myself observed a similar phenomenon in eight children who had recently been vaccinated but whose parents were HIV negative. The suspicions and fears that Proffesor Konotey-Ahulu mentioned are very real.

Competing interests:   I am the researcher and formulater of the mariandina nutritional immune boosting supplement that has been found valuable in the management of HIV/AIDS.


Prelude to Flegg's references 13 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Prelude to Flegg's references

Dear Editor,

Peter Flegg recently offered to provide references to support his statement that, "HIV is more efficiently transmitted in the acute phase of infection than subsequently." That, of course, assumes from the beginning that HIV is sexually transmitted. Recall that I began the current debate on the sexual transmission of HIV in late January with these words:

"I challenge Dr. Gareth Lloyd to come up with the names (even one will do) of the persons who are documented to have shown that AIDS (or even HIV) is sexually transmitted. I know of no such study. In fact, the scientific, medical literature is full of evidence that neither AIDS nor HIV is sexually transmitted. It is only assumed that they are."

It is now mid April and we still don't have those names. Therefore, I asked Flegg to "please provide the references that prove that HIV is sexually transmitted--efficiently or even inefficiently". In short, provide the evidence that HIV is sexually transmitted at all.

Instead of providing such references, Flegg says "Rasnick...now seems to want references for the evidence that HIV causes AIDS or that HIV is sexually transmitted. Rasnick has been given more than enough references concerning these facts in the past, not only during exchanges on fora such as the BMJ's rapid response section, but during his time on Mbeki's Presidential Panel."

It is true that Foley, Flegg and others have offered numerous references during the course of this debate but so far not one has come close to providing the proof or even likelihood that HIV or AIDS is sexually transmitted. After several exchanges it was grudgingly conceded by some of my opponents that the Padian et al. study [1] did not produce the evidence that HIV was sexually transmitted. Flegg attempts to skirt this fundamental problem by saying "Rasnick has been given more than enough references concerning these facts".

Peter Flegg, if not for me, then for the sake of the many observers of this debate who do not work on AIDS and who have not delved into the labyrinth of AIDS literature, could you please provide at least a short list of names of the individuals who have published the proof (along with the year of publication) that HIV and AIDS are sexually transmitted--and while you're at it, the names of those who proved that HIV causes AIDS? Since the contagious, sexually transmitted, HIV-caused AIDS dogma was set in stone in the 1980s, the proof (if it exists) should logically have been published some time in the 1980s.

Peter Flegg, do you dispute this reasoning? If you do, on what specific grounds? If the contagious/HIV hypothesis was not proved in the 1980s, then when and where was it proved?

With regards to the South African Presidential AIDS Advisory Panel, one of the reasons that Thabo Mbeki invited the mainstream AIDS doctors and scientists to share the same space with physicians and scientists from around the world who question, criticize and even dispute the contagious HIV hypothesis of AIDS was for the participants to challenge each other publicly to either prove their respective cases or disprove their opponents' claims. In the absence of proof for specific claims, the members of the panel were to come up with experiments and studies to settle the unanswered questions. The panel recommended 10 experiments and studies to test the fundamental assertions of the contagious/ HIV hypothesis of AIDS [2]. President Mbeki has authorized and provided funding for all ten.

I actively participated in the meetings in Pretoria and Johannesburg in 2000. During the entire process, I did not observe the mainstream members of the panel try to produce even a shred of evidence for the contagious/HIV hypothesis of AIDS. We minority members of Mbeki's Panel certainly pressed the mainstream for that evidence. Nor did they try to prove the dissidents wrong. The mainstream chose to remain silent on the disputed issues. Silence on such important issues is not a sign of confidence in one's position.

Here is a short list of what the mainstream members of Mbeki's AIDS Advisory Panel did not do. They did not attempt to provide the evidence that HIV is sexually transmitted. They did not attempt to show that AIDS is sexually transmitted. They did not attempt to show how or even that HIV causes AIDS. They did not attempt to show that the anti-HIV drugs do more good than harm. During both meetings, the mainstream members were present in body but not in spirit. Sitting at the table across from me, Luc Montagnier (the discoverer of HIV) actually fell asleep at one point during the meeting in Pretoria.

Flegg can't name the people who have shown that HIV or AIDS is sexually transmitted, or the people who have shown how HIV causes AIDS, or even name the people who showed that HIV causes AIDS--the most fundamental issue in dispute. Instead, he claims to know what went on at the meetings of Mbeki's AIDS Advisory Panel. I didn't recall Flegg participating in the Panel meetings so I searched the entire 134 page Interim Panel Report for his name and came up empty. A complete list of the participants follows the references. If he was in the audience, I can find no record of it.

Therefore, based on my first hand experience of what transpired in South Africa in May and July 2000, on what basis does Flegg claim that, "Rasnick has been given more than enough references concerning these facts...during his time on Mbeki's Presidential Panel"?

Next time I will analyze the references that Flegg cited that he claims "covers a spread of mutually-validating data [of] HIV's efficient [sexual] transmission in the acute stage of infection".

David Rasnick

References

1. Padian, N. S., et al. (1997) Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study, Am J Epidemiol 146, 350-357,

2. Secretariat for Thabo Mbeki. (2001), March, PRESIDENTIAL AIDS ADVISORY PANEL REPORT, Johannesburg, http:// www.gov.za/reports/index.html

Participants at the Presidential AIDS Advisory Panel meetings in South Africa, May and/or July 2000

Professor Salim S Abdool-Karim, Dr Stefano M Bertozzi, Dr Harvey Bialy, Dr Awa Marie Coll-Seck, Dr Etienne de Harven, Dr Ann Duerr, Professor Peter Duesberg, Dr Christian Fiala, Dr Helene Gayle, Dr Roberto A Giraldo, Dr ET Katabira, Dr Claus Koehnlein, Dr Manu VL Kothari, Dr Clifford Lane, Dr Marsha Lillie-Blanton, Dr Malegapuru W Makgoba, Professor Sam Mhlongo, Professor Ephraim Mokgokong, Professor Stephen Owen, Dr Jorge Perez, Dr David Rasnick, Mr David Scondras, Dr Joseph Sonnabend, Dr Zena Stein, Dr Gordon Stewart, Dr W Chalamira-Nkhoma, Dr Andrew Herxheimer, Proffesor Luc Montagnier, Dr Walter Prozesky, Dr Mark D Smith, Dr Stefano Vella, Dr Jose M Zuniga, Dr Stephen Chandiwana, Professor Roy Mugwera, Professor Eleni Papadopoulos-Eleopoulos, Prof Heinz Spranger, Dr Valender Turner, Professor Jerry Coovadia, Professor Charles Geshekter, Dr Glenda Gray, Dr Anthony Mbewu, Professor James McIntyre, Dr Lynn Morris, Dr Dan Ncayiyana, Dr Philip Onyebujoh, Dr Priscilla Reddy, Professor Barry Schoub, Professor Allan Smith, Dr Jimmy Volmink, Professor Allan Whiteside, Dr Carolyn Williamson, Mr Winston Zulu

Invited by the President but could not attend

Professor Francoise Barre-Sinoussi, Dr Robert Gallo, Dr Kaptue, Dr Souleymane M'Boup, Professor Fred Mhalu, Professor Valerie Mizrahi, Professor Pierre Mpele, Dr Paranjape, Dr Praphan Phanuphak, Professor Robert Root-Bernstein, Dr Kary Mullis

Competing interests:   None declared


Assumptions and opinions do not prove heterosexual transmission of HIV 15 April 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Perth, Western Australia,
John Papadimitriou, Barry Page, David Causer, Helman Alfonso

Send response to journal:
Re: Assumptions and opinions do not prove heterosexual transmission of HIV

The claim that HIV is heterosexually transmitted should not be accepted merely on the basis of assumptions and opinions

In Tony Floyd's Rapid Response "Most Experts Suggest 90% of African Adult HIV is from heterosexual transmission, Gisselquist 30%" (5th April 2003), he wrote "The fact that 'most experts claim it is 90%, and that Gisselquist thinks it approximately 30%, leads one to ask why he has been cited to support claims that HIV isn't sexually transmitted?"

It needs to be stressed that what "most experts claim" is only an assumption (as his quote from Gisselquist points out: "For more than a decade, most experts have assumed that more than 90% of HIV in African adults results from heterosexual transmission") as no proof has been provided.

Furthermore he quotes Gisselquist: "In this exercise, we show how data from studies of risk factors for HIV can be used to estimate the proportion from sexual transmission, and we present our estimates. Calculating two ways from available data, our two point estimates - we do not estimate confidence intervals - are that 25-29% of HIV incidence in African women and 30-35% in men is attributable to sexual transmission".

Apparently, Tony Floyd has only read the abstract from which he quoted. Had he read the article by Gisselquist he would have understood that various assumptions were made to obtain the stated estimate and that confidence limits could not be given. That is, it was only an "exercise" as stated to provide insight into estimates that could be obtained based upon the assumptions made. In the discussion section of the paper the authors wrote "We recognize that many questions can be raised about the data and about our procedures and we encourage those questions…We cannot and do not intend our estimates to be the last word, but rather a step toward better evidenced-based estimates of the proportions of HIV in Africa from sexual and other modes of transmission".

This is backed up in their conclusion where the authors wrote "There are many considerations — focused on specific parameters — that suggest that the estimates we present are too high or too low". Thus from this "exercise" nobody including Gisselquist has come to the conclusion that there is a 30% heterosexual transmission of HIV.

We neither misinterpreted nor falsely cited Gisselquist "to support claims that HIV isn't sexually transmitted" as Tony Floyd stated. This is the quote from Gisselquist, which we cited in our rapid response "HIV in South Africa" (13 March 2003): "HIV is not transmitted by 'sex', but only by specific risky practices". We gave the reference in our rapid responses of 13th March 2003 and 24th March 2003. We gave the reference again as well as its location in the article in our rapid response of 27th March 2003.

In Tony Floyd's Rapid Response of 7th April 2003 "Heterosexual Intercourse Found to be the Major Mode of HIV Transmission in a Group of Thai Fisherman", he wrote "Aside from David Gisselquist being falsely cited in support of alternative AIDS theories, the response entitled "HIV in South Africa" (1) provides another curious example. A 1994 article by Caceres CF and van Griensven was used to support a theory that ONLY anogenital insertive intercourse and oroanal sex are HIV risk factors." (italics ours)

Wrong. What Caceres and van Griensven wrote and we quoted was: "(1) unprotected anogenital receptive intercourse poses the highest risk for the sexual acquisition of HIV-1 infection; (2) anogenital insertive intercourse poses the highest risk for the sexual transmission of HIV-1 infection;… (5) no or no consistent risk for the acquisition of HIV-1 infection has been reported regarding other sexual practices such as anogenital insertive intercourse and oroanal sex".

Tony Floyd misleads by using the word "Found" in his title, since the authors did not claim to have "found" but merely "suggest that heterosexual intercourse is the major mode of transmission in this population". If Tony Floyd had read their paper rather than merely the abstract then he should have asked van Griensven the following questions:

• How is it possible that a sexually transmitted virus in gay men is only transmitted from the insertive to the passive partner but heterosexual Thai fisherman can get it from their passive partner?

• Why a test which is not good enough to prove HIV infection in Australia is good enough to prove HIV infection in poor Thai fishermen?

• How it is possible to claim proof for heterosexual transmission from a cross-sectional study? Especially when there are so many other risk factors.

We are very disappointed because it appears that Tony merely reads abstracts and then quotes from them out of context because he hasn't taken the time to read the papers themselves.

Competing interests:   None declared


Comments and an Analysis of Flegg's reference number 1 16 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Comments and an Analysis of Flegg's reference number 1

Peter Flegg continues to be frustratingly vague about his "facts". When I asked the simple question: where can one find the proof that HIV and AIDS are sexually transmitted?, he tries to skirt the awkward fact that the question remains unanswered by saying that, "[Rasnick] would only read into the data whatever he wishes to see. I [Flegg] have better things to do with my time than trot out a comprehensive list of references, only to see the material ignored, misquoted or misinterpreted".

Therefore, to save Flegg from trotting "out a comprehensive list of references" I once again ask only for the names of those people (even one name will do) who have proved that AIDS is contagious, sexually transmitted and caused by HIV. This does not seem to be an unreasonable request. As I recall, the Nobel committee can name no more than three people to share a single prize. So, Peter Flegg, what are the names of the people (up to three for each) who you would recommend to the Nobel committee for having shown that 1) HIV is sexually transmitted, 2) AIDS is sexually transmitted, 3) HIV causes AIDS? If it is impossible to come up with a list of these names, then can you give an estimate (an order of magnitude if necessary) of the minimum number of people that it took to prove each of the three mainstream assertions in question? After you have come up with this number (or even an estimate of its magnitude), would you kindly tell the observers of this debate exactly when and where the anonymous army of AIDS researchers marshaled the evidence, as you say, "to flog this particular horse [that] expired a very long time ago"? Who did the flogging, when and where did the execution take place? And, on what basis was the horse pronounced dead?

Second, Flegg accuses me of the sin he may himself be committing: "read[ing] into the data whatever he wishes to see". I am certainly guilty of ignoring some of the assertions and interpretations of individual papers--but not the data. Flegg accuses me of misquoting. I try very hard to quote people and texts accurately. Therefore, I ask Flegg to post the most egregious example(s) of where I misquoted him or others so that I can acknowledge the errors and correct them.

Third, the data are the data. It is largely a matter of judgment and taste as to whether data are being misinterpreted. Perhaps it is Flegg who is misinterpreting the data. Relying on their training, experience, and especially a critical eye, all scientists are not only free--but indeed obligated--to interpret the data as they see best. Multiple interpretations of the same phenomena are normal in science. In fact, there would be no science without different interpretations. When only one interpretation is allowed, science ends and dogma reigns.

Now let's examine reference number 1 that Flegg offered in response to my question: where is the evidence published in the scientific, medical literature that HIV is indeed sexually transmitted, whether early or late in infection?

Flegg says that Jacquez et al. [1] was "One [o]f the first papers to look at the contribution of early [sexual] transmission [and] concluded that chains of transmission grow rapidly, and this helps explain many observed population patterns for HIV infection (1)."

The first thing to note about the Jacquez et al. paper is that it was published in 1994, long after it had been pronounced that HIV was sexually transmitted and caused AIDS. Therefore, in order to get funded and published, Jacquez et al. were compelled to accept as axiomatic that HIV was sexually transmitted. They certainly did not attempt to test that belief. Within the constraints imposed by AIDS Inc., the authors were forced to come up with an explanation (no matter how ad hoc) for the very peculiar and truly unique Lazarus- like reemergence of HIV in AIDS patients a decade or more after they had developed immunity to the "deadly virus".

The very first paragraph of the Jacquez et al. paper sets the stage for their speculations: "Figure 1 shows scaled cumulative curves of the number of HIV seropositives obtained from the hepatitis B vaccine trial of the San Francisco City Clinic and from the Chicago MACS cohort. The epidemic curve for the San Francisco data was flattening by January 1983. The Chicago MACS cohort was at about the same point on its curve at the initial examination in September 1984...".

Thus, there was a rapid increase in the number of new HIV- positive (almost exclusively gay) men in San Francisco and Chicago beginning in the late 1970s that reached a plateau of short duration in the early 1980s followed by a steep decline to very low levels by the end of 1983. This scenario is not far removed from what one would expect for the spread of a new infectious agent in a closed population. It agrees with the so-called SIR dynamics, which stands for Susceptible, Infected, Recovered. In fact, the authors specifically state that, "the early spread of HIV may be viewed as the type commonly designated SIR or SEIR." The "E" stands for Exposed.

In order to explain the time course of HIV-antibody positives the authors speculated that: "High infectivity during the primary infection, followed by a long period of low infectivity, could give a rapid rising epidemic curve with sudden slowing of the process, i.e., an SIR dynamic. High activity groups are likely to have played an important role in the rapid rise. Other mechanisms that could have contributed to the sudden slowing are behavioral change to decrease risk and/or saturation of the high activity groups. Our goal is to examine the relative contributions of these mechanisms." But, since the HIV-antibody epidemic peaked before Robert Gallo had presented HTLV-III (alias HIV) to the world, the authors were forced to conclude that, "For the San Francisco epidemic and for the Chicago MACS cohort, behavioral change started too late to have much effect on the initial rapid rise."

Figure 1, as the authors state, was a cumulative curve. But, their Figure 3 shows the number of new HIV antibody positives for each year. The number of new cases rose from about 16 in mid 1978 to a plateau of around 400 from mid 1980 until the beginning of 1983 after which it dropped precipitously to 81 cases at the end of 1983. (In a previous letter I pointed out that there were fewer than 50 new AIDS cases--not HIV positives--in San Francisco in 2000 (the same level of AIDS cases seen in 1982) [2], and this was after three definition changes as to what constituted AIDS, each of which increased the number of new cases.) This peculiar situation led Peter Duesberg to quip that it was a good thing the Department of Health and Human Services had rushed to commit the US government into backing Robert Gallo's "deadly virus" as the cause of AIDS in April 1984 because if they had waited just a little longer there would have been no HIV epidemic to find.

Thus far in the Jacquez et al. analysis, HIV is behaving like a typical infectious agent. When it appears, it spreads rapidly and just as swiftly disappears as the infected individuals quickly develop immunity. If this scenario is correct, then why doesn't HIV cause AIDS during the period preceding the development of immunity? The authors find the answer to this important question in the AIDS catechism: "The difference with HIV is that the virus persists and gradually initiates a new process that leads eventually to immunosuppression with renewed infectiousness and ultimately death." The authors do not produce any evidence whatever to support their assertion, nor do they cite even a single reference to back it up. It is pure faith among the authors that this assertion, made by countless other AIDS researchers, must without question be true. Neither the authors nor Peter Flegg can tell us where we can find the proof for this central belief held by AIDS researchers, nor even give us the names of the people who may have produced that proof.

The rest of the lengthy paper by Jacquez et al. consists largely in arbitrarily adjusting a series of parameters so that their mathematical model could reproduce the broad features of the epidemiological data. As most everyone understands, a mathematical model is no better than the assumptions that go into it. As is typical of virtually all AIDS research, the authors neither included control experiments or studies. Absolutely crucial to the Jacquez et al. study would be a consideration of the accuracy of the HIV antibody testing that it relies on so heavily. However, the authors failed to take into account the well documented fact that vaccinations for hepatitis and other viruses [3-9], even hepatitis itself [10] among over 60 other diseases and conditions [11], will cause false positive antibodies to HIV. I have discussed in previous letters the serious problems with all surrogate testing for HIV and AIDS.

Analysis of the other references to follow.

David Rasnick

References

1. Jacquez, J. A., et al. (1994) Role of the primary infection in epidemics of HIV infection in gay cohorts, J Acquir Immune Defic Syndr 7, 1169-1184

2. Katz, M., et al. (2000)Quarterly AIDS Surveillance Report, San Francisco Department of Public Health, HIV Seroepidemiology and Surveillance Section, AIDS Surveillance Unit, www.dph.sf.ca.us/PHP/AIDSSurvUnit.htm

3. Lee, D. A., et al. (1992) HIV false positivity after hepatitis B vaccination, Lancet 339, 1060

4. Isaacman, S. H. (1989) Positive HIV antibody test results after treatment with hepatitis B immune globulin, Jama 262, 209

5. Pearlman, E. S., et al. (1994) False-positive human immunodeficiency virus screening test related to rabies vaccination, Arch Pathol Lab Med 118, 805-806

6. Proffitt, M. R., et al. (1993) Laboratory diagnosis of human immunodeficiency virus infection, Infect Dis Clin North Am 7, 203- 219

7. Challakere, K., et al. (1993) False-positive human immunodeficiency virus type I ELISA results in low-risk subjects, West J Med 159, 214-215

8. Mac Kenzie, W. R., et al. (1992) Multiple false-positive serologic tests for HIV, HTLV-1, and hepatitis C following influenza vaccination, 1991, Jama 268, 1015-1017

9. Hsia, J. (1993) False-positive ELISA for human immunodeficiency virus after influenza vaccination, J Infect Dis 167, 989-990

10. Sungur, C., et al. (1994) False-positive HIV antibody test following alpha-interferon therapy in a chronic hemodialysis patient, Nephron 67, 251

11. Johnson, C. (1996) Whose Antibodies Are They Anyway? Factors Known to Cause False Positive HIV Antibody Test Results, Continuum 4, 4-5

Competing interests:   None declared


Use of CONDOMS for heterosexual intercourse is HIGHLY EFFECTIVE IN PREVENTING HIV TRANSMISSION...... 17 April 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Use of CONDOMS for heterosexual intercourse is HIGHLY EFFECTIVE IN PREVENTING HIV TRANSMISSION......

Addressing comments above:

>Tony Floyd misleads by using the word "Found"

touche. I agree. 'Found' was too strong a word.

Perhaps the results of de Vincenzi's longitudinal study published in the New England Journal of Medicine(1) mean that she 'found' that:

---
"Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV."
---

Have not Peter Flegg and myself found numerous reasons as to why the Padian study does not support alternative AIDS theories? Looking up articles by Gisselquist, Brody, Baldwin and others certainly indicates that these authors do not support anything out of the ordinary, as claimed above.

>Had he read the article by Gisselquist he would have understood that various assumptions were made to obtain the stated estimate

I was under no delusions here at all! Of course Gisselquist's estimate of 30% heterosexual transmission of HIV and his statement that 'most experts' suggest 90% heterosexual transmission involved certain assumptions by the parties involved.

Whether it is approximately 30%, approximately 90%, or approximately something in between, this would (as supported by de Vincenzi) still be a lot more than precisely zero.

References:

(1) de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med. 1994 Aug 11;331(6):341-6. PMID: 8028613 [Abstract]

Competing interests:   None declared


Drifting in a state of denialist déjà vu. 18 April 2003
Peter J Flegg,
Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Drifting in a state of denialist déjà vu.

David Rasnick asks this of me: "Peter Flegg, if not for me, then for the sake of the many observers of this debate who do not work on AIDS and who have not delved into the labyrinth of AIDS literature, could you please provide at least a short list of names of the individuals who have published the proof (along with the year of publication) that HIV and AIDS are sexually transmitted--and while you're at it, the names of those who proved that HIV causes AIDS?"

Firstly, I doubt that there are "many observers" left to witness our exchange; indeed I would not be surprised if he and I were the only ones who have had the stamina to endure thus far.

Secondly, I must remind him that I entered this particular discussion to point out that HIV is more readily transmitted during the phase of primary HIV infection than subsequently. Why is Rasnick constantly repeating a demand of me for "proof" that HIV is sexually transmitted at all?

Has he already forgotten, or think we have forgotten that Brian Foley has already provided this evidence for him back in February? (1-4)? We all now seem to be drifting in a surreal state of denialist déjà vu. Perhaps Rasnick thinks that by vociferously demanding "proof" at sporadic intervals, new participants or readers of this discussion will be fooled into believing he has never been provided with any.

It would be more honest for Rasnick to say, "I do not accept the evidence you provide as sufficient proof" rather than to keep repeating "Provide the proof". Rasnick may not wish to accept what he has been given as evidence for the sexual transmission of HIV, but that is his personal choice, and there we will have to agree to differ. I suggest any neutral observers read the evidence for themselves and make up their own minds. Let them look at the articles from NIAID (5,6) as well as Brian Foley's extensive list of references for further evidence, if any is really needed.

1. http://bmj.com/cgi/eletters/326/7381/126/e#29017 2. http://bmj.com/cgi/eletters/326/7381/126/e#29095 3. http://bmj.com/cgi/eletters/326/7381/126/e#29307 4. http://bmj.com/cgi/eletters/326/7381/126/e#29416 5. http://www.niaid.nih.gov/factsheets/evidhiv.htm 6. http://www.niaid.nih.gov/factsheets/howhiv.htm

(Oh, and before Rasnick mentions it, I am aware that dissidents dispute the NIAID evidence)

How big does a "shred" have to be before it is noticed?

David Rasnick denies that he was given any evidence for the HIV hypothesis during either of the 2 meetings of Mbeki's Presidential Aids Advisory Panel in 2000. Rather than rely on memory, however, which as we can see can play anyone false, perhaps we should look at what the official report actually stated (1). Although produced by Mbeki's secretariat, the document takes great pains to demonstrate its impartiality and honesty in reporting the proceedings, so as not to be seen to be biased towards any side. I therefore accept its record as a true one, even though I was not there. Within the text I found the following examples:

"Proponents for the use of anti-retroviral drugs produced evidence that these drugs improve the quality of life of HIV-infected people" "Dr Williamson presented evidence that HIV is necessary and sufficient to cause AIDS but that cofactors increase the risk" "There are a large number of reports that have shown that transmission of HIV results in AIDS, and a number of examples where it has been proven, by characterising the virus in both the donor and the recipient, that transmission has occurred." "Dr Morris presented evidence to show that HIV is not an innocent bystander but a pathogenic virus that destroys the immune system." "Dr Williamson then covered evidence from animal models." "Prof Abdool-Karim quoted epidemiological evidence that HIV causes AIDS" "Extensive epidemiological evidence has shown that the detection of a number of AIDS cases in countries is preceded by the detection of HIV antibodies in the population." Dr Mossie reported that evidence for blood transmission had been derived from occupational exposure data, which the CDC had accumulated over time Studies conducted among drug users also proved that it was only when there was sharing of needles that HIV transmission occurred between them. Further evidence for blood-borne transmission has been derived from haemophiliacs who had contracted the virus from transfusion with infected blood products Drs Williamson and Gayle provided examples of healthcare workers who subsequently acquired AIDS from HIV transmission from accidental inoculation through contaminated instruments.

Rasnick now tells us (2): "I actively participated in the meetings in Pretoria and Johannesburg in 2000. During the entire process, I did not observe the mainstream members of the panel try to produce even a shred of evidence for the contagious/HIV hypothesis of AIDS."

And: "Here is a short list of what the mainstream members of Mbeki's AIDS Advisory Panel did not do. They did not attempt to provide the evidence that HIV is sexually transmitted. They did not attempt to show that AIDS is sexually transmitted. They did not attempt to show how or even that HIV causes AIDS. They did not attempt to show that the anti-HIV drugs do more good than harm. During both meetings, the mainstream members were present in body but not in spirit. Sitting at the table across from me, Luc Montagnier (the discoverer of HIV) actually fell asleep at one point during the meeting in Pretoria".

What exactly is Rasnick's definition of a "shred" of evidence? There seems to be a wide credibility gap between what Rasnick recalls took place and what the record states took place.

I suspect Luc Montagnier was not the only one to fall asleep.

1. http://www.polity.org.za/html/govdocs/reports/aids/aidspanel.htm 2. http://bmj.com/cgi/eletters/326/7387/495#31174

Oh, and for his information, it is HIV that is sexually transmitted, and not AIDS.

Competing interests:   None declared


Misquotations 18 April 2003
Peter J Flegg,
Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Misquotations

David Rasnick says: "Flegg accuses me of misquoting. I try very hard to quote people and texts accurately. Therefore, I ask Flegg to post the most egregious example(s) of where I misquoted him or others so that I can acknowledge the errors and correct them."

I have already pointed out to Rasnick (April 3rd) where he has deliberately misquoted me— I suggest he read my letter again.

For observers wanting a quick taste, here is a flavour:

"..HIV is maximally infectious during the acute phase of infection, and that many if not most transmissions occur during this period". (Flegg, March 30th)

"Flegg says after a short time following infection an HIV positive individual eventually fights off HIV and is thus unable to spread the infection". (Rasnick, April 1st)

Having already waited 2 weeks for a requested correction, I will not be holding my breath on this occasion.

Competing interests:   None declared


Re: Comments and an Analysis of Flegg's reference number 1 18 April 2003
Peter J Flegg,
Physician
BlackpoolVictoria Hospital, UK, FY3 8NR

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Re: Re: Comments and an Analysis of Flegg's reference number 1

It is usually a sign that someone is losing an argument when they feel the need to resort to ad hominem attacks questioning a researcher or his motives, rather than letting the research speak for itself. (Rasnick, http://bmj.com/cgi/eletters/326/7387/495#31248).

I wonder on what basis David Rasnick makes the accusation that "in order to get funded and published, Jacquez et al. were compelled to accept as axiomatic that HIV was sexually transmitted." I am used to hearing this perennial excuse being trotted out by dissidents ("there is a biomedical conspiracy ensuring that only those who have already accepted the "truth" of HIV can get research funding and publications"), but am surprised to see it being implicated here.

Having read his comments on the Jaquez paper (1), I am still not sure what Rasnick really thinks. On the one hand he seems to accept that the data demonstrate the infectious basis of HIV (since he admits "This scenario is not far removed from what one would expect for the spread of a new infectious agent in a closed population", and "HIV is behaving like a typical infectious agent"), but he also rejects the paper's conclusions.

Let others read this paper and see if their conclusions match the author's, or Rasnick's. Those reading this BMJ "debate" are not the usual bunch of gullible suspects with no scientific knowledge who trawl the web to find "publications" about AIDS conspiracies scattered among the stories of alien abductions, paranormal phenomena and similar pseudoscientific froth.

They are intelligent people with a medical background and some understanding of the concepts involved in studies such as these. Let them read the relevant papers and see if their conclusions match either the authors', or Rasnick's.

I eagerly await the promised re-interpretation of the next research paper in breathless anticipation.

(1) Jacquez, J. A., et al. (1994) Role of the primary infection in epidemics of HIV infection in gay cohorts, J Acquir Immune Defic Syndr 7, 1169-1184

Competing interests:   None declared


Conspiracy indeed! 18 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Conspiracy indeed!

Conspiracy indeed

Dear Editor,

Peter Flegg is annoyed that I bring out into the open the demonstrable fact that there is indeed a systematic refusal in the USA to fund and publish any work on AIDS that does not accept HIV dogma. Here is where Foley and Floyd's talents for doing PubMed searches would come in handy. Search for the number of scientific publications in mainstream journals studying or accepting HIV as the cause of AIDS. Then do the same thing for scientific publications in mainstream journals not studying or accepting HIV as the cause of AIDS. Then report the results in BMJ, one of the rare journals that permits free and open discourse and debate on AIDS. Let's see if there is numerical support for Flegg's faith in free and open access to the scientific journals to those who do not accept HIV dogma.

Peter Duesberg's experience provides numerical evidence that Flegg is wrong and that there is indeed a systematic denial of access to funding and publishing to those who do not accept HIV dogma. Duesberg is a member of the National Academy of Sciences in the USA and he cannot get any of his grant proposals funded because he disputes the contagious/HIV hypothesis of AIDS. Prior to Duesberg's critique of the pathogenicity of retroviruses, and HIV in particular (1), he did not have even one grant proposal turned down by any of the major funding sources. After that publication appeared, he has had 23 grant proposals in a row turned down and not one approved.

Through the end of 2003, US tax payers will have spent $118 billion on AIDS (2,3), and not one penny of that colossal figure went to researchers who do not accept HIV as the cause of AIDS. Because of this, Peter Duesberg has said "they could spend billions to study HIV on the moon or Jupiter if they wanted, but they can't afford $50,000 to prove themselves wrong." Flegg can find out the specifics of how Duesberg has been isolated and neutralized within scientific circles on pages 396-406 in his book Inventing the AIDS Virus (4).

Flegg doubts that conspiracy is behind the systemic denial of access to research funding and publishing by dissident scientists. But, shortly after Duesberg's paper appeared in Cancer Research, a memo was sent out from the office of the secretary of Health and Human Services under the heading "MEDIA ALERT". The memo noted that, "[t]he article apparently went through the normal pre- publication process and should have been flagged at the NIH" (4). No one bothered to ask: what business does a government agency have flagging any scientific paper? The memo pointed out the threat Duesberg posed for the government:

"This obviously has the potential to raise a lot of controversy (If this isn't the virus, how do we know the blood supply is safe? How do we know anything about transmission? How could you all be so stupid, and why should we ever believe you again?) and we need to be prepared to respond. I have already asked NIH public affairs to start digging into this." (5)

Copies of the memo were addressed to the secretary, under secretary, and assistant secretary of Health and Human Services, as well as the assistant secretary of public affairs, the chief of staff, the Surgeon General, and the White House (4).

One thing critics discover very soon is that the high priests of HIV dogma rarely if ever address the specific criticisms of the AIDS axioms. (Flegg, for example, completely ignores my specific and pointed questions.) Instead, they do everything possible to silence their critics. To save their careers most scientists stop asking embarrassing questions and prostrate themselves before the golden idol of HIV. The courageous (or stubborn, depending on you point of view) few who stick to their principles are forced to scrape up the money any way they can to do their research. Duesberg's lab, for example, relies on the generosity of wealthy individuals, private foundations, and general donations.

But even if you get the money to do the work, you won't be able to get your results published in American scientific or medical journals and you will no longer be invited to professional meetings. If you publicly question HIV dogma too loudly you risk ad hominem attacks and are accused of being a homophobe, or of encouraging people to stop taking AZT and the other DNA chain- terminating drugs (to which I plead guilty), or of causing people to stop using condoms.

Since the middle 1980s the United States has been engaged in a kind of medical McCarthyism, where anyone who asks questions about the HIV dogma is punished as a heretic. Those who are seen talking with a dissident are warned that they risk their careers and reputations if they continue. Even heads of state are not immune to threats and intimidation.

South African President Thabo Mbeki continues to receive intense personal attacks because he included on his AIDS Advisory Panel in 2000 a number of scientists and physicians from around the world who dispute the mainstream dogma of AIDS. Having failed to silence Mbeki, the AIDS establishment has orchestrated an international campaign to portray him as insane because he insists on getting answers to some very simple questions:

1) Why is AIDS in Africa so completely different from AIDS in the USA and Europe?

2) How does a virus know to cause different diseases on different continents?

3) How does a virus know if you are male or female, gay or straight, white or black?

Journalists who interview dissidents almost never see their work published or broadcast, they are no longer invited to mainstream meetings, and are vilified by former friends and colleagues.

On page 709 of his book Challenges (6), Serge Lang, the legendary Yale mathematician and member of the National Academy of Sciences, describes his unsuccessful effort to publish his commentary on Richard Horton's (editor of The Lancet) review of Peter Duesberg's book Inventing the AIDS Virus published in the New York Review of Books. Since the New York Review of Books would not publish his commentary, Lang sent a letter to the editor of The Lancet concerning the HIV scandal but it was turned down. He then sent a check along with his letter to have it published in the advertisement section of the journal. Yielding to Lang's persistence, the editor of The Lancet finally published Lang's letter (in the letters to the editor section) and returned his check.

There are countless more stories of censorship, intimidation, and financial and professional manipulation. But the discordant data still sits there, indestructible and unresolved.

With so many careers dependent on, and billions of dollars invested in, the HIV dogma and the axioms of AIDS, it is easy to see what is at stake. If some or all of the AIDS axioms are false (I'm certain that all of them are false), then we are faced with the biggest blunder of the 20th Century. It would require superhuman courage and integrity on the part of numerous government officials and the directors of the National Institutes of Health, the Medical Research Council, the World Health Organization, and the Centers for Disease Control, and of countless physicians, scientists, health care workers, journalists, celebrities and average citizens, to admit that they made a big mistake--that they got it all wrong about AIDS.

Many informed critics think that the billions of dollars at stake is the biggest roadblock to ending the AIDS insanity. That money is certainly a formidable weapon in the service of the HIV/AIDS establishment. However, I think it is simple human embarrassment that is the biggest obstacle to bringing this insanity to an end. It is the fear of being so obviously and hopelessly wrong about AIDS that keeps lips sealed, the money flowing and AIDS rhetoric spiraling to stratospheric heights of absurdity.

The physicians who know or suspect the truth are embarrassed or afraid to admit that the HIV tests are absurd and should be outlawed, and that the anti-HIV drugs are injuring and killing people. We are taught to fear antibodies, and to believe that antibodies to HIV are a harbinger of disease and death ten years in the future. When you protest this absurdity and point out to health care workers that antibodies are the very essence of anti- viral immunity your objections are met with either contempt or embarrassed silence.

The National Institutes of Health, the Centers for Disease Control, the Medical Research Council, and the World Health Organization are terrorizing hundreds of millions of people around the world by their reckless and absurd policy of equating sex with death. Linking sex to death has put these organizations in an impossible situation. It would be intolerably embarrassing for them to admit at this late date that they are wrong, that AIDS is not sexually transmitted. Such an admission could very well destroy these organizations or at the very least put their future credibility in jeopardy. Self preservation compels these institutions to not only maintain but to actually compound their errors, which adds to the fear, suffering, and misery of the world--the antithesis of their reason for being.

David Rasnick

PS: Flegg says that I misquoted him. However, that is not true. I did not quote Flegg but paraphrased his characterization when I said: If, as Flegg says, after a short time following infection an HIV positive individual eventually fights off HIV and is thus unable to spread the infection, then by definition that individual has become immunized against HIV. I did not put that in quotation marks. I did not quote Flegg as having said that.

1. Duesberg, P. H. (1987) Retroviruses as carcinogens and pathogens: expectations and reality, Cancer Res. 47, 1199-1220

2. Johnson, J. A. (2000) AIDS funding for federal government programs: FY1981-FY2001, Washington DC, Congressional Research Service, The Library of Congress, November 6, RL30731

3. HHS. (2002) Budget for HIV/AIDS Increases 8 Percent: Targets Expanded Efforts on Research, Washington DC, US Dept. of Health and Human Services, Feb. 4, Press release, http:// newsroom.hrsa.gov/releases/2002releases/HHSnews-HIV.htm

4. Duesberg, P. H. (1996) Inventing the AIDS Virus, Regnery Publishing Inc., Washington

5. Kline, C. (1987) MEDIA ALERT, memorandum of the office of the secretary, Washington, DC, Health and Human Services, April 28,

6. Lang, S. (1998) Challenges (Springer, Ed.), Springer, New York

Competing interests:   None declared


Re: Conspiracy indeed! 19 April 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK FY3 8NR

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Re: Re: Conspiracy indeed!

I never cease to be amazed at the degree of rampant paranoia and victimisation that threads through HIV dissidents' discussions about HIV research, its funding and its publication.

Since David Rasnick is involved in this discussion within the pages of the BMJ, perhaps he can ask Richard Smith what the journal's policy is on approving papers for publication, and what the view of other similar journals may be. I doubt that a Pubmed search for publications "for" and "against" HIV will tell us anything of note. Rasnick implies the numerical lack of papers "against" would corroborate his theory of a pro-HIV conspiracy. However, this would no more vindicate him than the lack of publications espousing a "flat earth" in geophysics journals would indicate a conspiracy against flat-earthers.

Apart from the allegations in Duesberg's book and some other indirect evidence Rasnick mentions, is there any real evidence that research concerning "alternative" theories on AIDS is deliberately not funded, or results unpublished? (Or is there only anecdote? - As a scientist I assume Rasnick would wish to see irrefutable evidence before making accusations - are there any controlled trials??? Any double-blind studies???) ;)

Let me remind everyone how we have arrived at our current state of knowledge concerning HIV. The initial years were full of uncertainties and a number of theories concerning the aetiology, epidemiology and transmission of the agent that causes AIDS competed for dominance. There are still contentious areas of debate, and such areas are fruitful targets for research (along with funding, and if appropriate, publication). Progress has been made largely through a process of inductive reasoning in keeping with the modern scientific method. The fact that there is now near -universal acceptance of HIV's existence and role in the pathogenesis of AIDS is the result of scientific consensus achieved because of the results of this research accrued over the years.

I know Rasnick refuses to accept it, but HIV causes AIDS. Why should precious funding be diverted to now try and disprove this fact? HIV ranks among the main threats to mankind, yet Rasnick seems to bemoan the fact that $118 billion has been spent on it. How much has the space programme consumed? How much does a war in Iraq cost? How much money poured into Duesberg's research coffers when he was fruitlesley chasing viral causes of cancer? Did he complain then that someone's research proposal on the wherabouts of Elvis was unable to get funding? Rasnick alleges that not a single penny has gone to fund those who dispute the orthodox view of HIV, but his letters are seemingly filled with references to publications supporting his views. (In my opinion these are usually incorrectly cited, but either way can Rasnick not see the inconsistency of his position here?)

Rasnick states: "It would require superhuman courage and integrity on the part of numerous government officials and the directors of the National Institutes of Health, the Medical Research Council, the World Health Organization, and the Centers for Disease Control, and of countless physicians, scientists, health care workers, journalists, celebrities and average citizens, to admit that they made a big mistake--that they got it all wrong about AIDS".

Has Rasnick never, ever contemplated the far more likely scenario, namely that he is the one who has got it all wrong, and that everyone else is right?

Rasnick again accuses me of ignoring his questions on the nature of HIV. He is ignoring my answers. I have shown him where to look, and pointed out that others before me such as Brian Foley have provided numerous references and sources. It becomes frustrating when the horse that one has led to water will not drink, but Rasnick, for all his proclaimed thirst, seems reluctant to even take the first few few steps towards the river.

Rasnick brings up the "simple" questions that President Mbeki asks. These are:

1) Why is AIDS in Africa so completely different from AIDS in the USA and Europe?

Answer: because differences in environment and pathogen prevalence determine the different manifestations of immunosuppression. For example, leukaemic children in Africa get different infections to leukaemic children in Norway. However they both still have leukaemia.

2) How does a virus know to cause different diseases on different continents?

Answer: see answer to 1) above. Remember, the virus causes immunodeficiency, and not the infections/diseases directly. And the diseases are not different; they just vary in geographic prevalence.

3) How does a virus know if you are male or female, gay or straight, white or black?

Answer: It doesn't. Its just a microorganism, like hepatits B, or syphilis, or malaria. The different prevalences for HIV depend upon many factors such as host genetic susceptibility, population demographics and dynamics, coinfection with other STDs, variation in sexual behavioural, variation in exposures through non-sexual routes, viral transmission dynamics,etc.

I can only presume that because hepatits B's epidemiology is similar to that of HIV, Rasnick/Mbeki must dispute its existence also. Or that because syphilis rates differ between races this means it is not sexually spread. Or because malaria affects Africans more than Europeans it must have a predeliction for dark skin.

Rasnick says (of HIV antibodies) "When you protest this absurdity and point out to health care workers that antibodies are the very essence of anti- viral immunity your objections are met with either contempt or embarrassed silence."

I am afraid that I have to meet this objection with contempt. I have lost count of how often Rasnick has had it explained to him, but antibodies merely indicate immune recognition. For chronic or latent infections they indicate ongoing infection (mainly because the immune response is not fully effective at eradicating the infection), and do NOT represent a cure. The repeated failure of a biomedical scientist to grasp this point after several attempts at explanation displays either a deliberate intent to remain in denial of the facts, or stupidity. Since Rasnick is obviously not stupid, I suspect the former explanation in his case. The embarrassed silence he experiences when raising his theory about antibodies with other health care workers is probably because they are too polite to correct the glaring errors in his logic.

Competing interests:   None declared


Analysis of Flegg's references 2-4 23 April 2003
David Rasnick,
Chief Science Officer, Boveran, inc.
San Ramon, CA 94583

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Re: Analysis of Flegg's references 2-4

Dear Editor,

In keeping with all references posted so far, none of Peter Flegg's references was designed to prove the sexual transmission of HIV. All authors have assumed from the start that HIV is sexually transmitted. To get around the awkward problem of having to say just when, where and by whom it was shown that HIV and AIDS were sexually transmitted, Flegg says that, "More direct evidence accrued for [the contribution of early sexual transmission] with the finding within the Swiss HIV cohort Study, which included 191 patients with PHI [primary HIV infection]. Through case contact tracing and nucleic acid sequence analysis it was demonstrated that onward transmission to another partner had occurred in 17 of these cases during the time of PHI [Flegg's reference (2)]" His reference 2 is Yerly, S. et al. HIV drug resistance and molecular epidemiology in patients with primary HIV infection. Abstract 754, 8th Conference on Retroviruses and Opportunistic Infections. Chicago 2001.

Since this is only a citation to a conference abstract I will not discuss it because there are no data or details to analyze.

Flegg went on to say that, "A detailed analysis of 5 heterosexual couples where transmission occurred clearly demonstrated the dynamics of early HIV transmission [Flegg's ref (3), reference (1) below]". However, Pilcher et al.'s "detailed analysis" amounts to a short letter to the editor of only five paragraphs, which was published in 2001. Their letter does not claim to offer proof that HIV is sexually transmitted because the authors are compelled to assume that from the start since it had been declared to be true back in the 1980s. They report on only "5 cases drawn from 4 university hospital clinics, in whom sexual transmission was suspected to have occurred between an individual with documented PHI [primary HIV infection]. We defined PHI as p24 antigen positivity, RNA and/or DNA positivity, enzyme-linked immunosorbent assay negativity, or 2 or fewer bands on Western blot within 30 days." In short, these 5 HIV-negative cases (as the authors' criteria specify) were considered to be infected with HIV not on the basis of being antibody positive to HIV but to being positive for p24 antigen and by the so-called viral load test. Furthermore, these 5 couples were assumed to have gotten infected with HIV through sex. Before considering p24, let's first examine the PCR viral load's ability to detect infectious HIV since, after all, it is only infectious virus that can be transmitted.

Pilcher et al. do not provide experimental details in their short letter. Therefore, we do not know how they measured HIV RNA or DNA. Since (to the best of my knowledge) the Roche viral load test is the only one approved by the FDA, I will assume that they used the Roche test. Recall that on March 7, 2003, I posted a letter titled "An Abuse of surrogate markers for AIDS". I quoted from the third paragraph of the insert that comes with Roche's viral load test, which says: "AMPLICOR HIV-1 MONITOR Test is not intended to be used as a screening test for HIV or as a diagnostic test to confirm the presence of HIV infection" (Roche Diagnostic Systems AMPLICOR HIV-1 MONITOR Test package insert, PMA No. BP950005/4). Yet, Pilcher et al. offered not one word of justification for using RNA and DNA measurements to label someone as being infected with HIV.

Also in the March 7, 2003, letter I listed numerous references to false positives resulting from the viral load test. I will restate only one of the quotes here: "The availability of sensitive assays for plasma HIV viral load and the trend toward earlier and more aggressive treatment of HIV infection has led to the inappropriate use of these assays as primary tools for the diagnosis of acute HIV infection. ...Physicians should exercise caution when using the plasma viral load assays to detect primary HIV infection... Plasma viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV infection..." (2).

Flegg can read the other quotes from my March 7 letter that throw into serious doubt the use of PCR viral load as a measure of infectious HIV or anything else for that matter.

Since the viral load test is not a reliable measure of infectious HIV, the only thing left to Pilcher et al. as a measure of infectious HIV was the presence of p24 antigen in the blood of their five cases. It is surprising that Pilcher et al. even tried to use p24 antigen to indicate the presence of infectious HIV since it was discredited for that purpose a decade ago (3). Kaplan et al. (4) and Kageyama et al. (5) have demonstrated that simply measuring the amount of p24 antigen present does not necessarily indicate the level of infectious HIV even in cell culture, where HIV does not have to contend with the immune system.

Flegg says that the biological evidence linking higher rates of sexual transmission of HIV with high levels of HIV can be found in Rakai, Uganda, as reported by Quinn et al. (6). As is typical of much of AIDS research, Quinn et al. piggybacked their study onto one that was designed to address a different question from the one they were interested in. Quinn et al. retrospectively selected 415 discordant HIV-seropositive couples from a 1994-1998 Wawer et al. study of 15,127 individuals from Rakai, Uganda (7). The intention of the Wawer et al. study had been to reduce HIV incidence by mass treatment of STDs with conventional antibiotics. More about this study below.

As Quinn et al. acknowledged, their respective "study differs from other investigations that selectively identified and followed HIV-1 discordant couples." The authors are probably referring to Padian et al. (8) and similar studies but they don't tell us. As is customary in AIDS research, the presence of HIV infection was presumptively determined by testing for antibodies to HIV and or using the Roche Amplicor viral load test. Again, as is typical of AIDS publications, there was no discussion of the appropriateness of using these tests to diagnose HIV infection (both of which are specifically not approved for detecting HIV infection) or even of the limitations of their accuracy under the specific conditions prevailing in sub- Saharan Africa. Because Quinn et al. were looking only for and thinking only of sexual transmission of HIV, they automatically assumed that the appearance of antibodies to HIV in their discordant couples (after retrospective analysis) had to be from sexual transmission.

The lack of consideration of the appropriateness and accuracy of the HIV antibody and viral load testing may explain the otherwise inexplicable results reported by Quinn et al. The authors reported that "22 percent of the HIV-1-negative partners seroconverted during the course of the study, for an overall incidence of 11.8 per 100 person-years."

But surprisingly, "There were no significant differences in the rate of acquisition of HIV-1 infection according to either the presence or absence of symptoms of sexually transmitted diseases or the presence or absence of syphilis, gonorrhea, Chlamydia, trichomonas, and bacterial vaginosis." There was also "no significant difference in risk of infection among HIV-1 negative partners according to the level of formal education, history of travel outside the district within the previous year, the number of sexual partners within the past year (one vs. two or more), or condom use or nonuse."

These results were completely contrary to the expectations outlined in the first paragraph of the introduction: "A wide variety of behavioral and biologic risk factors are associated with the risk of transmission, including the frequency and types of sexual contact, the use or nonuse of condoms, immunological status,... and sexually transmitted diseases."

The discordance between results and expectations only gets worse when the entire Wawer et al. study population is taken into consideration. The rationale behind the Wawer et al. study (7) was that reducing STDs (which was assumed to be a co-factor in the transmission of HIV) should reduce the transmission of HIV. However, the result of the study was paradoxical. While the investigators were very successful in significantly reducing STDs, their intervention had "no [effect] on incidence of HIV-1 infection..." (7).

The results of Wawer et al. were no fluke. An even more recent study by Kamali et al. "showed that in a "community-randomised trial in rural southwestern Uganda, behavioural and STI interventions were associated with an increase in condom use with the last causal partner--a proxy measure for consistent condom use in high-risk encounters, and substantial reductions in incidence of active syphilis and prevalence of gonorrhoea. There was also evidence...of reduced incidence of HSV2--a proxy measure of unprotected sexual contact, and increased recognition of symptoms of STIs... . These effects were not translated into any measurable reduction in HIV-1 incidence over a median follow-up of 3-6 years" (9).

In South Africa, pregnant women were tested for syphilis and antibodies to HIV in order to see how the two diseases were correlated by geographical location and over time. But, there was no correlation (10). On the contrary, KwaZulu-Natal, which is leading when it comes to HIV, has the lowest rate of syphilis in all provinces. Western Cape, on the other hand, had the highest rate of syphilis in 2000 but the lowest HIV prevalence. Northern Cape had the highest rate of syphilis in 2001 but the third lowest prevalence of HIV antibodies in that year. Paradoxically, then, there is an inverse geographical correlation between syphilis and HIV although both are said to be transmitted by heterosexual intercourse. An even more extraordinary result is the divergence over time between an increasing prevalence of antibodies to HIV and a declining rate of syphilis (10). This is also difficult to understand given the assumption that both are sexually transmitted.

The data from Thailand show that these paradoxical results are not peculiar to Africa. Even though Thailand is said to be severely hit by a heterosexually transmitted HIV-epidemic, we find yet again the same scenario presented by South Africa and Uganda. Bangkok has the highest rate of STDs but low HIV prevalence. Conversely, the so called Golden Triangle of northern Thailand has the highest rate of HIV but the second lowest STD morbidity of all regions. And, even within the different provinces of the Northern Region there is a negative correlation between HIV and syphilis (11). The conclusion from these observations is obvious: HIV cannot be heterosexually transmitted.

About the only thing Quinn et al. can find that correlates with the rate of appearance of antibodies to HIV in discordant couples are the numbers produced by the viral load test. In addition to the problems discussed above and in my March 7, 2003, letter, the viral load test in the Quinn et al. study was not performed during the study but actually one year after its completion. Furthermore, the authors did not perform the obvious control of performing the viral load test on the HIV-negative partners. This, at the very least, would provide a negative control, which is certainly called for given Flegg's reference to Pilcher et al. who had HIV antibody negative but viral load positive individuals (1).

AIDS researchers chronically assume too much.

David Rasnick

References

1. Pilcher, C. D., Eron, J. J., Jr., Vemazza, P. L., Battegay, M., Harr, T., Yerly, S., Vom, S., and Perrin, L. (2001) Sexual transmission during the incubation period of primary HIV infection, Jama 286, 1713-1714

2. Rich, J. D., and et al. (1999) Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case study, Annals of Internal Medicine 130, 37-39

3. Papadopulos-Eleopulos, E., Turner, V. F., and Papadimitriou, J. M. (1993) Is a positive Western blot proof of HIV infection?, Biotechnology 11, 696-707

4. Kaplan, A. H., Zack, J. A., Knigge, M., Paul, D. A., Kempf, D. J., Norbeck, D. W., and Swanstrom, R. (1993) Partial inhibition of the human immunodeficiency virus type 1 protease results in aberrant virus assembly and the formation of noninfectious particles, J Virol 67, 4050-4055

5. Kageyama, S., Hoekzema, D. T., Murakawa, Y., Kojima, E., Shirasaka, T., Kempf, D. J., Norbeck, D. W., Erickson, J., and Mitsuya, H. (1994) A C2 symmetry-based HIV protease inhibitor, A77003, irreversibly inhibits infectivity of HIV-1 in vitro, AIDS Res Hum Retroviruses 10, 735-743

6. Quinn, T. C., Wawer, M. J., Sewankambo, N., Serwadda, D., Li, C., Wabwire-Mangen, F., Meehan, M. O., Lutalo, T., and Gray, R. H. (2000) Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group, N Engl J Med 342, 921-929

7. Wawer, M. J., Sewankambo, N. K., Serwadda, D., Quinn, T. C., Paxton, L. A., Kiwanuka, N., Wabwire-Mangen, F., Li, C., Lutalo, T., Nalugoda, F., Gaydos, C. A., Moulton, L. H., Meehan, M. O., Ahmed, S., and Gray, R. H. (1999) Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group, Lancet 353, 525-535

8. Padian, N. S., Shiboski, S. C., Glass, S. O., and Vittinghoff, E. (1997) Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study, Am J Epidemiol 146, 350-357

9. Kamali, A., Quigley, M., Nakiyingi, J., Kinsman, J., Kengeya- Kayondo, J., Gopal, R., Ojwiya, A., Hughes, P., Carpenter, L. M., and Whitworth, J. (2003) Syndromic management of sexually- transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial, Lancet 361, 645-652

10. Makubalo, L. E., Netshidzivhani, P. M., Mulumba, R., Levin, J., du Plessis, H., Ratsaka, M., Mahlasela, L., Mudzanani, L., Johnson, C., and Shikweni, F. (2001) Summary Report:NATIONAL HIV AND SYPHILIS SERO-PREVALENCE SURVEY IN SOUTH AFRICA, Pretoria, South Africa, Directorate: Health Systems Research, Research Coordination and Epidemiology, http:// 196.36.153.56/doh/index.html

11. Chitwarakorn, A. e. a. (1998) Sexually Transmitted Diseases in Asia and the Pacific, Ministry of Public Health, AIDS Division, HIV/ AIDS Situation in Thailand, Region 10, Chiang Mai, Thailand

Competing interests:   None declared


CONSPIRACY THEORY??? 23 April 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

Send response to journal:
Re: CONSPIRACY THEORY???

At my University we are almost indoctrinated with a distrust of Pharmaceutical Companies. Hell I'm a card-carrying member of nofreelunch.org!

Most Doctors that I've spent time with think little of the Government or big business.

These disparate groups could not coordinate the proverbial in a brothel, let alone dupe the entire world into some sort of orchestrated suppression of the 'hidden truth' about any pathology as suggested, especially one as unfortunately omnipresent as HIV/AIDS.

Of course you would expect anyone involved in a conspiracy to deny that they are part of one. Hence it is best to 'fess up. That's right, I'm part of it. :)

Or perhaps those that are pointing the finger have several pointing straight back at them?

Being a much smaller group of people it would be far more feasible for them to the conspirators! Perhaps what is really going on is a Conspiracy to Fabricate a Conspiracy Theory or a CFCT.

You heard it here first.

So when the scientific world fails to embrace my all natural patented 3000C potentised herbal virgin yak fat infusion theory I'll have something to fall back on. The Medical Establishment (you know, them) will be implicated in my very own CFCT!

Cheers

Tony

Competing interests:   None declared


A critical examination of the evidence for the existence of HIV 25 April 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics,Royal Perth Hospital, Western Australia 6001,
Valendar F. Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: A critical examination of the evidence for the existence of HIV

A critical examination of the evidence for the existence of HIV

In his rapid response "For some people it's April Fool's day all year round" (3 April 2003) with regards to the Padian study, Peter Flegg wrote "I explicitly stated that "there was a low transmission rate" in her study…". It must be pointed out that in the prospective study of 175 HIV—discordant couples, tested every six months, not one of the 175 non-infected men or women became HIV positive. That is, the prospective Padian study did not prove a low transmission rate but a zero transmission rate, that is, no transmission.

As far as Peter Flegg being perplexed about the thinking of "dissidents", does he expect all scientists to think alike? Science develops by a diversity of views and by questioning existing paradigms. While we agree with the main views held by other "dissidents", that is, there is no proof that HIV cause AIDS, there are also differences. We also agree with some views held by the "HIV" experts including the following:

  • We agree a positive antibody test in individuals from the AIDS risk groups indicates a propensity for the development of some diseases. However, nowhere in the scientific literature is there evidence that a positive test proves HIV infection. In other words, the antibody test is similar to the erythrocyte sedimentation rate (ESR), a laboratory test of considerable clinical utility that predicts the onset or presence of illness and whose level is used to monitor the natural history or treatment of diseases. Nonetheless, it is devoid of specificity.
  • Public Health Policy — like the "HIV" experts, we believe safe sex is necessary for the prevention of AIDS. In fact we go one step further. The HIV experts advise safe sex need be practised only with a positive partner. We say safe sex should be practised with all partners irrespective of antibody status.

Like the "HIV" experts, we are all for clean needles and again we go one step further. Since, in our view it is the content of the syringe, that is, the recreational drug injected which is one of the primary causes, the best way to prevent AIDS is to avoid all injections.

  • Like the "HIV" experts we do not believe in conspiracy theories.

Peter Flegg also wrote we claim that HIV "spreads through anal intercourse". In fact, in one of our rapid responses we wrote "It is also our view that a positive antibody test ("HIV") is acquired by the same means, that is, passive anal intercourse."( 24th March 2003) In another rapid response we wrote "all the presently available data prove it is only passive anal intercourse which is the risk factor for the acquisition of a positive antibody test." (1st April 2003.) This means that either HIV is the only unidirectionally spread STD in the history of medicine or whatever causes the positive antibody test cannot be an infectious agent.

It is true that in some of our articles, to present our argument we have assumed the existence of HIV in order to show how such an assumption leads to untenable claims for the HIV theory of AIDS.

Peter Flegg wrote that we have been "asserting that HIV does not exist". Peter Flegg may have interpreted our published material in this manner but it is important to state that we have never said HIV does not exist. Rather, from the very beginning when Montagnier and Gallo published their studies in 1983/1984, we have consistently argued that neither their data nor anybody else's prove that HIV exists. (This issue can be resolved by performing experiments. This is exactly what we argued for and what was accepted by both sides at the Presidential AIDS Panel Meetings held in July 2000, Johannesburg, South Africa http://aidsmyth.addr.com/panelreport.htm). Some of the reasons can be found in what follows.

INTRODUCTION

Following the appearance of AIDS in 1981 many aetiological factors were proposed. In May 1983 Montagnier announced the discovery of a retrovirus, now known as HIV, from lymphatic tissue of a gay man with lymphadenopathy. One year later Gallo reported data which "suggests that HTLV-III [HIV] is the primary cause of AIDS". By 1986 the scientific community accepted the Gallo assertion that the same data was "clearcut evidence" that HIV is the causative agent of the clinical syndrome. Even today the five Science papers published by these French and American groups are still widely regarded as proving beyond all reasonable doubt that HIV exists and is the cause of AIDS.

However, not all scientists accepted these findings. In 1987 Peter Duesberg published an invited paper in Cancer Research on retroviruses and cancer in which he also questioned the role of HIV in AIDS. At the same time one of us (EPE) also challenged the theory including the data claimed to prove the existence of HIV. Papadopulos-Eleopulos also proposed an alternative, non-infectious aetiology and treatments based on this hypothesis. Since then our group has published papers addressing every facet of the HIV theory including a detailed examination of HIV isolation and the HIV genome. Here we confine ourselves largely to addressing the data published by Montagnier and Gallo in their 1983/84 Science papers. Genomic data are only briefly discussed because the existence of HIV and the HIV theory of AIDS were universally accepted before such data were available. For a comprehensive discussion on genomic data the reader is referred to reference 19.

RETROVIRUSES AND THEIR IDENTIFICATION

A virus possesses two characteristic properties. The first is anatomical, that is, being a microscopic particle of individual morphology, the second, the ability to generate identical progeny by synthetic processes obligatorily occurring within living cells. It is the latter attribute which defines a particle with the appearances of a virus, that is, a viral-like particle, as infectious and thus a virus. The three subfamilies (0ncovirinae, Lentivirinae and Spumavirinae) of Retroviridae (Retroviruses) are "enveloped viruses with a diameter of 100-120 nm budding at cellular membranes. Cell released virions contain condensed inner bodies (cores) and are studded with projections (spikes, knobs)". The retroviral particles contain RNA and the enzyme reverse transcriptase (RT), an RNA dependent DNA polymerase which catalyses the synthesis of DNA contrary to the central dogma of biology, that is, in a direction "reverse" from DNA to RNA. According to retrovirologists, such DNA is then integrated into existing cellular DNA as a "provirus". Retroviral particles share the property of concentrating (banding) at a density of 1.16 gm/ml when centrifuged at high speeds in sucrose density gradients, a fact long used in their purification.

All retrovirologists agree that to prove the existence of a new retrovirus one must isolate it. However, the term "virus isolation" is beset with semantic difficulties and ambiguities. The dictionary meaning of "isolation" derives from the Latin insulatus (made into an island) and refers to the act of separating an object from all other matter that is not that object. "Purification" means to obtain something free from impurities. In this context isolation is the same as purification. Because virus particles are small it is not possible to obtain a single, isolated particle. The next best thing is to obtain a mass of particles separate from everything else. Until the early 1980s, for the isolation of animal retroviruses as well as the "first" human retrovirus HL23V, by isolation retrovirologists meant purification. On the other hand, nowadays both basic and specialised texts rarely define "isolation" and when they do such attempts are non-illuminating. For example, Levy defines isolation as a "sample of a virus from a defined source", and White as the ability to "identify a totally unforeseen virus, or even discover an entirely new agent". Encompassed as "virus isolation" are listed methods of culturing specimens in tissue and chick embryo cells, as well as live animals, following by documentation therein of cytopathic and pathological effects, haemoabsorption, immunofluorescence, antigen/antibody reactions and "characterisation of the viral genome". HIV experts, including Luc Montagnier and Robin Weiss define "virus isolation" as "propagating them [viruses] in cells in culture" and see www.theperthgroup.com/aids/vftweiss.html. However, if "virus isolation" is to "take a sample of a virus from a defined source", or "propagating them in cells in culture", then first one must have prior proof that a virus exists in "a defined source" or "in cells in culture". One cannot know that a virus exists or define its constituents without purification (isolation) of the putative viral particles.

There are several reasons why this is mandatory:

To prove that the retrovirus-like particles are infectious, that is, they are a virus

The finding of particles with the appearances of retroviruses, is not proof that such particles are retroviruses and even less proof a particle is a particular retrovirus. Particles bearing the morphological characteristics of retroviruses are ubiquitous. In the 1970s such particles were frequently observed in human leukaemia tissues, cultures of embryonic tissues and "in the majority if not all, human placentas". Type-C retroviral particles are present in "fish, snakes, worms, pheasant, quail, partridge, turkey, tree-mouse and agouti" as well as in "tapeworms, insects...and mammals". Gallo was well aware of this problem as far back as 1976 when he wrote: "Release of virus-like particles morphologically and biochemically resembling type-C virus but apparently lacking the ability to replicate have been frequently observed from leukaemic tissue". In other words, it is not possible to claim a particle is a retrovirus merely by appearances. To prove that retrovirus-like particles observed in a culture are a virus one must isolate the particles, characterise their proteins and RNA and introduce the particles into a secondary culture. If any particles are released in the secondary culture they too must be isolated and proven that their proteins and RNA are the same as those from the primary culture. In such experiments one must not ignore the use of legitimate controls and in doing so take in consideration an important difference between retroviral and other infectious agents.

When one finds an infectious agent, for example a virus or a bacterium, either in vitro or in vivo, one may be assured that the agent has been introduced into the culture or animal from outside. Retroviruses are the exception. This is because normal human and animal genomes contain information which, under the appropriate conditions, leads to the synthesis of retroviral RNA and proteins, or even to the assembly of retroviral particles, that is, to the expression of endogenous retroviruses. And although as late as 1994 both Gallo and Fauci taught "there are no known human endogenous retroviruses", it is known that at least 1% of the human DNA is retroviral DNA and that endogenous retroviruses are present "in all of us". Furthermore, new endogenous retroviral genomes may arise from rearrangements of existing retroviral genomes, cellular DNA or both, caused by many factors, including pathogenic processes. The expression of endogenous retroviral genomes may arise spontaneously and may be significantly accelerated and the yield increased by conditions which induce cellular activation. According to the eminent retrovirologist George Todaro, "the failure to isolate endogenous viruses from certain species may reflect the limitations of in-vitro cocultivation techniques". Endogenously produced retroviruses are morphologically and biochemically indistinguishable from exogenous retroviruses. Because of this, the finding of identical retrovirus in serially "infected" cultures/cocultures is not proof that the cells are infected with exogenous retrovirus. One method which may assist resolve but will not prove whether cells acquire virus from the outside (exogenously acquired retrovirus, infectious retrovirus) and have not assembled a retrovirus from information already existing in normal cells (endogenous retrovirus), is to conduct control cultures/cocultures in parallel with test cultures/cocultures. The only difference between test and control cultures should be the introduction of tissue assumed infected into the test cultures. In every other respect control cultures must be dealt with identically. For example:

  1. because detection of RT and retroviral genetic sequences, and release of retroviral particles depends on the metabolic state of the cells, the physiological state of the cells used in the control cultures should be as close as possible to the test culture;
  2. because the mere act of co-cocultivation may lead to release of endogenous retroviral particles, if test cells are cocultured, so should the controls;
  3. extracts even from normal, unstimulated cells when added to the cultures may increase endogenous retroviral expression. Because of this, when host cells are cultured with supernatant or material which bands at 1.16 gm/ml from cultures thought to be infected, the controls must be cultured with similar material from noninfected cultures;
  4. since the appearance of endogenous retrovirus can be accelerated and the yield increased a million fold by stimulating the cultures with mitogens, mutagens, chemical carcinogens and radiation, if test cultures are exposed to or employ such agents so should the controls;
  5. to avoid observer bias and in the best interests of science, blind examination of test and control cultures/cocultures should be performed.

To determine their biological effects

Without recourse to pure particles it is impossible to determine whether effects are due to virus particles or contaminants including "chemical stimulants", a caveat stressed as far back as 1911 by the Peyton Rous, the father of retrovirology.

In 1911 Rous induced malignancy in chickens by injections of cell-free filtrates obtained from a muscle tumour. Similar experiments were repeated by many researchers and the tumour inducing filtrates became known as filterable agents, filterable viruses, Rous agents, Rous virus and ultimately retroviruses. However, Rous himself expressed doubts that the agents which caused the tumours were infectious in nature. Indeed he warned, "The first tendency will be to regard the self-perpetuating agent active in this sarcoma of the fowl as a minute parasitic organism. Analogy with several infectious diseases of man and the lower animals, caused by ultramicroscopic organisms, gives support to this view of the findings, and at present work is being directed to its experimental verification. But an agency of another sort is not out of the question. It is conceivable that a chemical stimulant, elaborated by the neoplastic cells, might cause the tumour in another host and bring about in consequence a further production of the same stimulant".44

To characterise the viral proteins

The only way to prove that a protein is a constituent of an object is to obtain it from that object, or when the object is very small as is the case of viruses, from material consisting of purified virus particles. If the material contains impurities which are proteins or contain proteins, it is not possible to determine which are viral and which are not. Yet only after the viral proteins are characterised is it possible to employ them as antigens in antibody tests.

To characterise the viral genome

As for viral proteins the only way to prove that a stretch of RNA is viral it is to obtain it from material which contains nothing else but virus particles. If the material contains impurities the impurities must not include RNA. Then and only then can the RNA and its complementary DNA (cDNA) be used as probes and primers for genomic hybridisation and PCR studies.

To act as a gold standard for the antibody tests

The reaction of a virus or viral protein with an antibody present in a patient's serum does not prove that the antibody is induced by or directed against the virus or a viral protein. That is, it does not prove the reaction is specific. This is because there are significant obstacles which hinder the interpretation of antibody/antigen reactivity including non-specific stimulation, cross-reactivity or both. Cross reactivity results from antibody molecules, even monoclonal antibodies, interacting not only with the inducing antigen but also with other antigens. Indeed, there are instances where "cross-reactive antibodies may have higher affinity with antigens other than the inducing antigen. Even antigens that differ for most of their structure can share one determinant, and a monoclonal antibody recognising this site would then give a 100% cross-reaction. An example is the reaction of autoantibodies in lupus with both DNA and cardiolipin...It should be emphasised that sharing a "determinant" does not mean that the antigens contain identical chemical structures, but rather that they bear a chemical resemblance that may not be well understood, for example, a distribution of surface charges". Since polyclonal antibodies are composites of monoclonal antibodies these facts apply equally, if not more so, to polyclonal antibodies. These facts have been extensively exploited in clinical medicine for the diagnosis of diseases such as syphilis and infectious mononucleosis. In these diseases, T. pallidum and Epstein-Barr virus cause the appearance of antibodies reactive with ox-heart proteins and sheep and horse red blood cells. However, this does not mean that patients are "infected" with ox-heart, or horse red blood cells and the diseases are induced by these agents. The only way to determine the specificity of an antibody/antigen reaction is to use an independent method, a gold standard to prove the presence or absence of the antigen. The only possible gold standard for a test to prove a virus infection is the virus in question. That is, virus isolation/purification.

METHODS FOR THE ISOLATION/PURIFICATION OF RETROVIRUS-LIKE PARTICLES

Up till the 1950s retroviruses were isolated/purified by filtration although this method was less than satisfactory. With the development of the electron microscope, apparently, for some retrovirologists, the detection of retrovirus-like particles was deemed sufficient to prove the existence of a retrovirus. However, other scientists including the well-known retrovirologist, JW Beard, recognised that cells, including uninfected cells, under various conditions, were responsible for the generation of a heterogenous array of particles some with the appearances of retroviruses. Beard stressed: "identification, characterisation, and analysis are subject to well-known disciplines established by intensive investigations, and the possibilities have by no means been exhausted. Strangely enough, it is in this field that the most frequent shortcomings are seen. These are related at times to evasion of disciplines or to their application to unsuitable materials. As was foreseen, much of the interest in the more tedious aspects of particle isolation and analysis has been diverted by the simpler and undoubtedly informative processes of electron microscopy. While much can be learned quickly with the instrument, it is nevertheless clear that the results obtained with it can never replace, and all too often may obscure, the need for the critical fundamental analyses that are dependent on access to homogenous materials" (italics ours).

By the 1970s there was general agreement that "Virions of RTV [retroviruses] have a characteristic buoyant density, and centrifugation to equilibrium in density gradients is the preferred technique for purification of RTV". The method of banding in density gradients is not ideal either. Substances other than retroviruses may band at the same density. This is why at a meeting held at the Pasteur Institute in 1972, Francoise Barre-Sinoussi and Jean-Claude Chermann stressed that to claim purification of retrovirus-like particles using sucrose density gradients it is absolutely necessary to prove, using the electron microscope, that the 1.16 gm/ml band contains nothing else but particles with "no apparent differences in physical appearances".

THE PHENOMENA CLAIMED TO PROVE THE EXISTENCE OF HIV

In May 1983 Luc Montagnier, Francoise Barre-Sinoussi, Jean-Claude Chermann and colleagues published a paper in Science entitled, "Isolation of a T-Lymphotropic retrovirus from a patient at risk for Acquired Immune Deficiency Syndrome (AIDS)". This is the paper which, since the resolution of the polemics between Montagnier and Gallo concerning allegations of misappropriation by the latter of the French virus sent to the US by the Pasteur Institute, is accepted as being the study which proved the existence of HIV. There it was shown that mitogen stimulated lymph node cell cultures from a gay man (BRU) with lymphadenopathy were able to transcribe the synthetic RNA primer-template An.dT15. From this data Montagnier and his colleagues concluded that BRU's lymph node cells were infected with a retrovirus. The finding of the same activity in the supernatant of a coculture consisting of the same cells with stimulated lymphocytes from a healthy individual was considered proof for virus transmission as well as isolation. In another experiment supernatants from the cocultures were added to two, three day old, stimulated umbilical cord lymphocytes cultures. "Electron microscopy of the infected umbilical cord lymphocytes showed characteristic immature particles with dense crescent (C-type) budding at the plasma membrane". Supernatant from the culture was banded in sucrose density gradient and the 1.16 gm/ml band was shown to transcribe An.dT15. The proteins in the 1.16 gm/ml band as well as the proteins of a cellular extract were separated according to their molecular weight using "denaturing buffer and electrophoresed on 12.5 percent polyacrylamide-SDS slab gel". When the strips were incubated with human sera many proteins from the cellular extracts were found to react with serum from BRU, another gay man as well as a "healthy donor". In the strips containing the proteins from the 1.16 gm/ml band three proteins including a p25 ('p' for protein, 25 for its molecular weight in thousands) were found to react. They also reported that the p25 did not react with antibodies to HTLV-I. The material banding at 1.16 gm/ml was claimed to be "purified, labelled, virus" although no electron microscopic data were presented. The authors concluded: "A retrovirus belonging to the family of recently discovered human T-cell leukaemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24".

Robert Gallo and his associates did not consider the Montagnier group data as proving "true isolation". As late as 1997, in a book published by one of the best known HIV experts, Jaap Goudsmit, one reads: "The BRU lymph node was first cultured in early January 1983 and, on January 15, it shed an enzyme absolutely unique to the lentivirus group. [The enzyme is not even specific to retroviruses much less to Lentiviruses (see below)]...The BRU virus grew slowly and with difficulty, but its identity and activity were reported in the May 20, 1983 issue of Science...The Pasteur Group was widely acclaimed but very worried. In the world of virology, finding a new virus is not enough: You must propagate and isolate the organism for analysis by other virologists. The French had not yet isolated their new lentivirus".

Why then did: (a) Gallo, who reviewed the Montagnier manuscript, recommend its publication? (b) all the HIV experts including Gallo and Goudsmit (on page 24 of his book one reads: "BRU was the first strain to be isolated") accept that the first isolation of HIV and thus of its existence was proven in the May 1983 Science paper?

A year later, in May 1984, Gallo, Popovic and their colleagues published four papers in Science in which they claimed "isolation" of another retrovirus from AIDS patients. However, in addition to the use of a leukaemic cell line, the only difference between the Montagnier and Gallo groups' data were quantitative. In the first paper entitled "Detection, Isolation and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and pre-AIDS", (HTLV-III=HIV), experiments were described in which "concentrated culture fluids harvested from short-term [mitogenically stimulated] cultures of T-cells" from patients with AIDS or pre-AIDS were cultured with a mitogenically stimulated leukaemic cell line HT and highly selected clones obtained by culturing HT with irradiated cells of a healthy donor. The data presented as proof of isolation of HIV were: (a) RT activity in cell free supernatants and the 1.16 gm/ml band; (b) reaction in the cultures with "Rabbit antiserum to HTLV-III" and "Patient serum (E.T.)"; (c) EM showing the presence of retroviral-like particles in the cultures.

An enquiry conducted by the National Institutes of Health Office of Scientific Integrity found that the HT cell line was cultured not with concentrated fluids (supernatant) originating from individual AIDS patients, but with concentrated fluids pooled initially from individual cultures of three patients and ultimately from the individual cultures of ten patients. In evidence given to this enquiry the reason given was because none of the supernatants "individually was producing high concentrations of reverse transcriptase". In other words, Gallo and his colleagues did not regard the levels of RT from individual cultures as proof that individual specimens contained a retrovirus. The Gallo investigation found the pooling of specimens to be "of dubious scientific rigor". One scientist described the procedure as "really crazy". Most importantly how could Gallo use the reaction with rabbit antiserum to prove HIV isolation (purification) when, to obtain rabbit antiserum rabbits must first be injected with pure HIV? It is inexplicable how Gallo and his colleagues could already possess "Rabbit serum to HTLV-III" before they had proved the existence of a novel virus. However, if the antiserum was manufactured "from rabbits infected repeatedly with disrupted HTLV-III", that is, the material banding at 1.16 gm/ml, one would expect to obtain antibodies to all the proteins constituting this material even if the proteins were cellular and not viral.

In the second paper entitled "Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from patients with AIDS and at risk of AIDS", Gallo and his colleagues claimed to have "isolated" HTLV-III (HIV) from 26/72 (36%) of AIDS patients. In this paper isolation was defined as "more than one of the following": "repeated detection of a Mg2+-dependent reverse transcriptase activity in supernatant fluids; virus observed by electron microscopy (EM) [retrovirus-like particles in the culture]; intracellular expression of virus-related antigens detected with antibodies from seropositive donors or with rabbit antiserum to HTLV-III; or transmission of particles". Transmission of particles was defined as "detected by RT assays or by electron microscopic observation, to fresh human [umbilical] cord blood, bone marrow, or peripheral blood T lymphocytes", cultured with supernatants from the "infected" cultures. (It can be seen that the Gallo group method permitted "isolation" of a retrovirus without evidence for either particles or RT).

In the third paper, proteins from the 1.16 gm/ml band which they claimed was "purified" HIV, as well as the proteins from the "infected" cells, were "lysed and fractionated by electrophoresis on a 12% polyacrylamide slab gel in the presence of SDS. The protein bands were electrophoretically transferred to a nitrocellulose sheet" and reacted with different sera. In other words Gallo used a technique which is known as Western blot (WB) antibody test. Many proteins from the cellular extract were found to react with sera from both patients and healthy individuals. They also reported that two proteins from the 1.16 gm/ml band, p24 and p41, reacted with patient sera. For this and no other reason it was claimed that "these molecules are the major components of the virus preparation. p24 and p41 may therefore be considered the viral structural proteins". As far as morphology is concerned, the Gallo group reported that the HIV particle "is produced in high numbers from infected cells by budding from the plasma membrane. A possible unique feature of this virus is the cylindrical shaped core observed in many mature virions...HTLV-III is a true member of the HTLV family". (HTLVs are type C retroviral particles and not Lentiviruses as HIV is claimed to be).

In the fourth paper, instead of separating the proteins which banded at 1.16 gm/ml and then incubating them with patient sera, the mixture of all proteins was used, that is, they performed a test known as enzyme-linked immunosorbent assay (ELISA). "To understand the molecular nature of the antigens recognised by ELISA", they also performed WB, with some of the sera. They reported that: "Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus…The data presented here and in the accompanying reports suggest that HTLV-III is the primary cause of AIDS". Two years later Gallo wrote that "The results presented in our four papers provided clearcut evidence that the aetiology of AIDS and ARC was the new lymphotropic retrovirus, HTLV-III"67 (italics ours).

COMMENTS

As mentioned, apart from the quantitative difference, the Gallo group experiments are no different from those performed by Montagnier and his colleagues. It follows then, that if Montagnier's group data do not prove "true isolation" neither did Gallo's nor anybody else's because to date everybody has repeated (for the vast majority only part thereof) the same experiments as these two groups. It is of pivotal significance that neither group reported the use of valid controls (see above) nor did they prove they had obtained purified retrovirus-like particles. The question then is, do the data obtained by the Montagnier and Gallo group, that is RT, particles in culture and antigen/antibody reactions prove the isolation of a unique, or even a retrovirus, any retrovirus?

Without doubt, if by isolation one expects proof of purification, then the detection of an enzyme, or retrovirus-like particles in a culture, or proteins either in the cells or the 1.16 gm/ml band which react with antibodies present in human or animal sera, do not comply. To argue otherwise one must define the detection of cardiac or hepatic enzymes in the blood of patients suffering chest pain or jaundice as proof for isolation of the human heart or liver. Likewise, if an antibody/antigen reaction is proof for isolation of a virus then antibody reactivity to the protein βHCG is proof for isolation of the human placenta. The assertion that the detection of a retrovirus-like particle in a culture proves isolation is no different from asserting that the detection of a fish-like creature in the ocean is the same as having a definite fish in your frying pan. The detection of RT, retrovirus-like particles and antibody/antigen reactivity can only be considered proof for the detection of a retrovirus, and then if, and only if, there is prior knowledge that the three phenomena are specific to retroviruses.

To claim that the detection of this phenomena proves the existence of a new retrovirus one must have proof that at least one of the three phenomena is different from that observed in all other known retroviruses.

Reverse transcriptase

At present some of the leading HIV researchers consider RT as being the "sine qua non" of retroviruses and regard the detection of reverse transcription in lymphocyte cultures from AIDS patients not only as proof of the presence of such viruses but of HIV itself including HIV isolation and quantification. However, according to some of the best known retrovirologists including its discoverer, as well as the Nobel Laureate and former Director of the US National Institute of Health Harold Varmus, reverse transcriptases are present in all cells as well as bacteria and viruses. "Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years, evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transcriptional events that include both viral and nonviral genetic entities". Even if RT were a property only of viruses it is not specific to retroviruses. According to Varmus, "Reverse transcription was assigned a central role in the replication of other viruses [hepatitis B and cauliflower mosaic viruses] and in the transposition and generation of other kinds of eukaryotic DNA". "The hepatitis B viruses (HBVs) are small DNA viruses that produce persistent hepatic infections in a variety of animal hosts and replicate their DNA genomes via reverse transcription of an RNA intermediate. All members of this family contain an open reading frame (ORF), "P" (for pol), which is homologous to retroviral pol genes" [pol=polymerase]. "Hepatitis B virus (HBV) resembles retroviruses, including HIV, in several respects. In particular, both viruses contain reverse transcriptase, and replicate through an RNA intermediate". Because of this, it has been suggested that hepatitis B infection should be treated with the same antiretroviral agents as HIV infection.

At present, evidence exists which shows that although the major target organ for hepatitis B virus is the liver, cells other than hepatocytes "including peripheral blood lymphocytes and monocytes, may become infected with HBV". Lymphocyte stimulation in general and PHA (an agent employed in the majority of cultures with tissues from AIDS patients), is associated with the production of hepatitis B virus from peripheral blood lymphocytes in patients infected with HBV including "viral replication in chronic hepatitis B infection of childhood". Hepatitis B virus infection is widespread in the AIDS risk groups.

In the early 1970s Gallo proved that cultures of leukaemic cells transcribe the An.dT15 template-primer as does material banding at 1.16 gm/ml originating from "PHA stimulated (but not unstimulated normal human blood lymphocytes". Reading the Gallo 1984 Science papers the impression is gained that the leukaemic HT cell line and thus its clones, including H9 which Gallo used, was a new cell line developed in Gallo's laboratory. However it is now known that the HT cell line is the HUT78 cell line which originated from a patient with adult T cell leukaemia, a disease which Gallo claims is caused by the retrovirus, HTLV-I. A year earlier Gallo claimed to have proven that the HUT78 cells are infected with HTLV-I. If this is the case, the Gallo group would have detected RT in their cultures even if the enzyme is specific to retroviruses and the cultures were not infected with HIV. Other researchers reported RT activity in normal non-infected spermatozoa.

It must also be pointed out that the presence of HIV reverse transcriptase was detected by both Montagnier and Gallo, (and all HIV experts since) indirectly, that is, by detecting the transcription of the template-primer An.dT15. However, at least in 1984 if not 1983, Montagnier and his colleagues knew that in the 1970s there was proof that "Among a number of template primers, (rA)n.(dT)12-18 has been most frequently employed since RT shows high activity with this template primer. However, the problem is that the cellular DNA polymerases (pol b and pol g ) also effectively utilize the same template primer". In fact, in 1975, an International Conference on eukaryotic DNA polymerases defined DNA polymerase γ as the cellular enzyme which "copies An.dT15 with high efficiency but does not copy DNA well". One year earlier Gallo wrote: "Under appropriate reaction conditions DNA polymerase β can efficiently transcribe poly (A) primed by oligo (dT)". Thus it is possible to detect transcription of An.dT15 even when no RT, either viral or cellular, is present, especially under the conditions used to prove the existence of HIV. (Both Montagnier and Gallo accept that the phenomena detected in cultures which are said to prove HIV isolation cannot be detected unless the cells are chemically stimulated). Nowadays the non-specificity of RT is broadcast even in the popular press to readers contemplating the purchase of shares in biotechnology companies.

In conclusion, even if one accepts Montagnier and Gallo's groups' definition of isolation, given that RTs and reverse transcription are nonspecific to retroviruses, their detection even in an unlimited number of consecutive cultures/co-cultures cannot be considered proof for isolation and propagation of a retrovirus.
"HIV" particles

Montagnier and his colleagues reported HIV initially as a type C particle, then as a type D particle and then as a Lentivirus. In 1984 Gallo and his colleagues reported HIV as a type C particle. However, in 1985 Gallo wrote: "A possible unique feature of the virions is the cylindrical core observed in many presumably mature virions. Virions having this type of core have been frequently reported for certain type D retroviruses, and in some instances, for type C retroviruses". Jay Levy reported HIV as a type D particle. Others at the University of California wrote that "AIDS virus isolated show morphologic characteristics of type C, type D and Lentiviruses". According to Anthony Fauci and others" "T-cells and macrophages handle the virus very differently. In the T-cell, virus buds out of the external plasma membrane of the cell. In the monocyte/macrophage cultures it buds into membrane-bound vesicles inside the cells". The latter is a description of a type A, retroviral particle. Thus the leading HIV experts have described HIV as a member of two subfamilies and three genera of Retroviridae. These taxonomical differences imply that if HIV was a newly discovered mammal, it could have been either human, a gorilla or an orang-utan. By consensus at present HIV is regarded as a Lentivirus. This agreement was reached when it was realised that in "HIV" positive individuals AIDS did not appear soon after "infection", although the designation Lentivirus is a morphological description.

"HIV infected cultures" contain in addition to the particles with the morphology attributed to HIV many other "viral particles". For example: Hockley and his colleagues from the Electron Microscopy and Photography Section and Division of Virology at the National Institute for Biological Standards and Control in the United Kingdom describe a profusion of particles which they divide broadly into three groups, mature, ring-like and small with spikes. The mature particles "were approximately spherical in shape and 100 to 150nm in diameter. The outer lipid membrane was frequently broken or absent in places, and there was no evidence of surface spikes...A few mature particles were found that were larger than average and appeared to contain a double nucleoid...in the preparation of HIV there were always many vesicles with granular contents in which it was not possible to recognise a distinct nucleoid". Also, "The ring-like particles had a more consistently spherical shape and were larger (140nm in diameter)" and the small particles "were unusually spherical but sometimes slightly angular in shape and 65 to 90nm in diameter" and had spike-like projections on their surface. Hans Gelderblom who has done most of the EM studies in HIV/AIDS research reported that although Lentiviruses and thus HIV is considered to have a cone shaped core, he and his colleagues found centrosymmetric and tubular cores as well. The caption to one photograph reads: "Virions can be seen having either elongated, 'baton-like' tubular cores 30-35nm in diameter or containing more than one core. Tubular and regular cone-shaped cores can coexist within one virion". The text states: "Rarely, tubular core structures reminiscent of batons with a diameter of 30-35nm and a length of 150-250nm are observed". Lekatsas and other virologists from Pretoria and Johannesburg reported: "We used the characteristic cylindrical structure in the core as an identifying characteristic for the virus to distinguish it from cellular debris and also noted that it may vary considerably in its dimensions and morphological features. We have found two basic virus particle sizes, 90nm and 120nm, both present in large numbers. The larger particle bears no surface projections while the smaller particle is rarely 'naked' and usually bears projections". The US CDC reported: HIV particles are "usually round and have a diameter of about 85-95nm...Virus with bar-shaped nucleoids and particles with a tear-drop shape are commonly seen in HTLV-III/LAV infected lymphocytes, sometimes ring-shaped particles without dense nucleoids are also seen". The question then arises if the particles with the "unique" morphology considered to be HIV represent an exogenous retrovirus originating from tissues of AIDS patients or those at risk, then what is the origin and role of the many non-HIV particles and which, if any, of the "HIV" or non-HIV particles band at 1.16 gm/ml? That is, which have the density characteristic of retroviruses? Retrovirus-like particles have been found in non-HIV-infected cord blood lymphocytes cell cultures and in cells used for HIV "isolation" such as and H9 (HUT-78), CEM, C8166 and EBV transformed B-cells. Retrovirus-like particles antigenically related to HIV have been found in cultures of salivary gland extracts from patients with Sjorgen's syndrome. In the only EM study, either in vivo or in vitro in which suitable controls were used and in which extensive blind examination of controls and test material was performed, particles indistinguishable from "HIV" were found in 18/20 (90%) of AIDS as well as in 13/15 (87%) of non-AIDS related lymph node enlargements. This led the authors to conclude: "The presence of such particles do not, by themselves indicate infection with HIV".

It is of pivotal significance to note that:

  1. As Hans Gelderblom and his colleagues pointed out in 1998, to date nobody has reported the presence of "infectious plasma HIV".
  2. In no "HIV-infected" cultures are there particles which display both principle morphological characteristics of retroviruses, that is, "a diameter of 100-120nm" AND surfaces which "are studded with projections (spikes, knobs)". The electron microscopist agree that the "HIV" particles are devoid of knobs and thus of the "HIV" protein gp120 (see below) said to be the constituent protein of the knobs.

Hans Gelderblom and his colleagues have estimated that immediately after being released from the cell membrane "HIV particles" possess an average of 0.5 knobs per particle which are rapidly lost, but also pointed out that "it was possible that structures resembling knobs might be observed even when there was no gp120 [knobs] present, i.e. false positives". Yet all HIV experts agree that the infectivity of the HIV particles is determined by the gp120 (knobs). Thus, according to Montagnier et al, "The gp120 is responsible for binding the CD4 receptor" while for Matthews and Bolognesi, "First gp120 binds to the CD4 receptor on an uninfected cell; then gp41 becomes anchored in the adjoining membrane; next the two membranes begin to fuse, and the virus spills its contents into the cell". Callebaut et al state, "The human immunodeficiency virus (HIV) infects lymphocytes, monocytes, and macrophages by binding to its principal receptor, the CD4 molecule, through the viral envelope glycoprotein gp120. The V3 loop of gp120 is critical for HIV infection". Others are in complete agreement.

The general agreement that gp120 (knobs) is absolutely necessary for HIV particles to be infectious and the fact that this protein (knobs) is not present in the cell free particles leads to one unavoidable conclusion, that is, the "HIV" particles are not infectious, they are not viral particles. Furthermore,

  1. To infect umbilical cord lymphocytes and the HUT-78 cells Montagnier and Gallo used cell-free fluids (supernatants). Montagnier cultured umbilical cord lymphocytes with supernatant from the cocultures of lymphocytes from BRU cultured with lymphocytes from a healthy individual. Gallo cultured the HUT-78 cell line with supernatants from the cultures of ten "infected" individuals. Even if the supernatants contained particles, being cell free the particles would be devoid of knobs (gp120), that is, they would not have been infectious. This means that even if Montagnier and Gallo had proof that their umbilical and HUT-78 cloned cultures contained particles with all the morphological characteristics of retroviruses, that in sucrose density gradients the particles banded at the 1.16 gm/ml band and the band contained nothing else but particles, the particles could not have originated from their patients. Furthermore, since the only samples which the Pasteur Institute gave to the Gallo laboratory were cell free, one must question the basis upon which Gallo was accused of misappropriation of the French virus.
  2. It is generally accepted that haemophiliacs are infected with HIV by contaminated factor VIII. However, to date nobody has reported the presence of "HIV" particles in plasma. Even if such particles were present the particles would be devoid of gp120. Since gp120 is "crucial to HIV's ability to infect new cells" it is not possible for haemophiliacs to be infected with HIV through factor VIII administration. There is another fundamental reason why it is impossible for haemophiliacs to be infected with "HIV" from "contaminated" factor VIII. According to a publication from the CDC,112 "In order to obtain data on the survival of HIV, laboratory studies have required the use of artificially high concentrations of laboratory grown virus...the amount of virus studied is not found in human specimens or any place else in nature,...it does not spread or maintain infectiousness outside its host. Although these unnatural concentrations of HIV can be kept alive under precisely controlled and limited laboratory conditions, CDC studies have shown that drying of even these high concentrations of HIV reduces the number of infectious viruses by 90 to 99 percent within several hours. Since the HIV concentrations used in laboratory studies are much higher than those actually found in blood or other body specimens, drying of HIV-infected human blood or other body fluids reduces the theoretical risk of environmental transmission to that which has been observed--essentially zero". Given that factor VIII is dispensed as a freeze-dried powder which spends many weeks or months waiting use, it is incomprehensible that the CDC and others continue to regard patients with haemophilia at risk for HIV infection via contaminated factor VIII concentrates and enigmatic that another explanation for "HIV" and AIDS in haemophiliacs has not been sought.4

The only conclusion one can draw from the electron microscopy data is that the reported particles are non-HIV or even retroviral specific which means that the detection of such particles, be it in an unlimited number of consecutive cultures/cocultures, is not proof for isolation, no matter how isolation is defined.

Furthermore:

  1. Even if reverse transcriptase activity and retrovirus-like particles are specific to retroviruses, they are not specific for a unique retrovirus. The only evidence both groups presented for the existence of a unique retrovirus, HIV, is the antigen/antibody reaction, as acknowledged by both Montagnier and Gallo.
  2. It is accepted that the finding of a retrovirus in culture, especially under the conditions used by Montagnier and Gallo is not proof that the retrovirus is present in vivo. The only evidence which both Gallo and Montagnier's groups presented for the existence of HIV in vivo was the antigen/antibody reaction.
  3. Even today the only evidence given as proof that HIV is the cause of AIDS is a "correlation" between the antibody test and the appearance of AIDS.

It is obvious that:

  1. the Montagnier and Gallo interpretation of the antigen/antibody reaction is crucial for the HIV hypothesis of AIDS and in fact for the existence of a unique retrovirus, HIV;
  2. if the interpretations are not correct, one would have no choice but to question not only the HIV hypothesis of AIDS but also the existence of HIV.

"HIV" antibodies

It has already been mentioned that the mere interaction between an antigen such as a protein or a virus and an antibody does not prove any more than a chemical relationship. In all other aspects the reaction may be totally nonspecific. To prove the specificity of the reaction one must employ an alternative, independent method of proving the existence of the antigen, that is, one must use what is generally known as a gold standard. The only possible gold standard for the HIV antibody tests (the antigen/antibody reaction) is HIV itself, that is, HIV isolation. No matter how one defines isolation, obviously the definition cannot include the antibody/antigen reaction (the antibody test, neither the WB nor the ELISA) because, by doing so, not only does one not have an independent analysis, the test becomes its own gold standard and is thus rendered meaningless. Reading the 1984 Gallo Science papers it appears that Gallo always defined isolation as "more than one of the following: reverse transcriptase activity either in the supernatant or the 1.16 gm/ml band; retrovirus-like particles in the culture or reaction between proteins (either in the cultured cells or the 1.16 gm/ml band) with antibodies present in the patients sera or "antiserum to HTLV-III". However, in an interview Gallo gave to Huw Christie, the editor of the British magazine Continuum, at the 1998 Geneva AIDS Conference, Gallo said, "Sometimes we had Western Blot positive but we couldn't isolate the virus. So we got worried and felt we were getting false positives sometimes so we added the Western Blot. That's all I can tell you. It was an experimental tool when we added it and for us it worked well because we could isolate the virus when we did it". In other words:

  1. In 1984 Gallo knew that to prove the specificity of the antibody test one must use a gold standard.
  2. The gold standard had to be HIV isolation.
  3. Although it is not known how he and his colleagues initially defined isolation, the definition did not include the antibody/antigen reaction (the Western Blot). This means that Gallo and his colleagues were aware that an antibody/antigen reaction cannot be used as proof for isolation. Yet, by the time their Science papers were published, and in order to reconcile the low correlation between what they initially called isolation and the antibody/antigen reaction, arbitrarily, and against all scientific reasoning, they "added the Western Blot" to their definition of isolation. (It is interesting that even with their novel definition the correlation between "isolation" and antibody tests was still less than perfect. They "isolated" HIV from 26/72 (36%) of patients with AIDS, while 88% of patients with AIDS were seropositive using an antibody test Gallo considered highly specific).

In an interview which Montagnier gave to the French Journalist Djamel Tahi in 1997, he stated: "analysis of the proteins of the virus demands mass production and purification. It is necessary to do that". Indeed, the only way to prove that a protein is a viral constituent is to obtain it from material which contains nothing else but viral particles. Instead Montagnier's and Gallo's groups incubated the proteins which banded at 1.16 gm/ml with sera from AIDS patients. The proteins which were found to react more often with the sera were said to be HIV proteins (although neither group published any evidence for the existence of retrovirus-like particles, pure or impure, at the 1.16 gm/ml band); and the antibodies to be HIV antibodies. However, even if the antigen/antibody reaction is 100% specific, that is, antibodies react only with inducing antigens and with no other, from such a reaction it is impossible to determine the origin even of one reactant much less the origin of both the antigen and the antibody. Let us consider differing scenarios:

  1. Both Gallo and Montagnier had proof that the 1.16 gm/ml band contained nothing else but retrovirus particles and that their antibodies reacted specifically with their proteins. According to Montagnier, in the cultures which contain cells originating from patients with adult T4 cell leukaemia, as did Gallo's HUT-78 cell line, "it is a real soup" of retroviruses. Indeed, even if the cultures do not harbour HIV they will harbour HTLV-I and, given the condition used by Gallo and the fact that the cells were leukaemic, they may also contain endogenous retroviruses. According to one well known HIV expert, Myron Essex, 35% of AIDS patients possess antibodies to HTLV-I. (In the same issue of Science in which Montagnier published his isolation of "HIV", Gallo published three papers claiming isolation of HTLV-I from AIDS patients suggesting this retrovirus was the cause of AIDS). According to another equally as well known HIV expert, Reinhard Kurth, from the Paul-Ehrich Institute in Germany, 70% of "HIV-positive patients" have antibodies which react with the retrovirus HTDV/HERV-K, an endogenous retrovirus, or, as Kurth put it, a retrovirus present "in all of us". Thirty seven per cent of HIV positive individuals were also found to have antibodies to type D retroviruses whereas HIV is claimed to be a Lentivirus. Although Montagnier's cultures may not have contained HTLV-I, the result may still have been "a real soup" of endogenous retroviruses especially if one considers their culture conditions and the cells used, umbilical cord lymphocytes, which have been shown to release retrovirus-like particles even when not infected with HIV. Since we cannot obtain the proteins from each particle and characterise them, the next best thing is to take the mass of particles, disrupt their proteins and position them in an electrophoretic strip according to their molecular weights. Although we know that the proteins in the strip are retroviral, we have no way of determining which protein belongs to which retrovirus if more than one retrovirus is present at the 1.16 gm/ml band. When the proteins are incubated with sera, we may find some of the proteins react. From such a reaction we will be able to say that the antibodies and obviously the proteins are viral but we cannot determine which protein belongs to which virus and by which virus the antibodies were induced. We will be definitely wrong if we consider such a reaction proof that the 1.16 gm/ml band: (a) contains only one retrovirus; (b) the retrovirus is a new exogenous retrovirus, HIV; (c) the proteins are the HIV proteins; (d) the antibodies are HIV antibodies; (e) these data are proof that the patient is infected with HIV even if the antibody antigen reactions are specific.
  2. Both Montagnier and Gallo had proof that the vast majority of the 1.16 gm/ml band was composed of retrovirus particles but that the band also contained non-retroviral material. This material could have been of cellular origin (cellular constituents also band at 1.16 gm/ml) and may be of bacterial, fungal and viral origin (constituents of the many infectious agents other than retroviruses, known to be present in the cultures and the patients). It is a fact that in the USA, Europe and Australia individuals with AIDS as well as those at risk have antibodies to many infectious agents including viruses such as EBV, CMV and hepatitis B virus. Evidence also exists which shows that individuals with AIDS and those at risk have circulatory immune complexes, rheumatoid factor, anti-nuclear, anti-cellular, anti-platelet, anti-red cells, anti-actin, anti-tubulin, and anti-myosin antibodies. Montagnier himself demonstrated that individuals with AIDS and those at risk have high levels of antibodies to the ubiquitous cellular protein actin whose molecular weight is 41,000, as well as to another ubiquitous protein, myosin, which has two sub-units of molecular weights, 18,000 and 25,000. Anti-lymphocyte antibodies have been found in 87% of patients who have a positive "HIV" antibody test and their levels correlate with clinical status. It is also acknowledged that Africans with AIDS and those at risk are infected with many agents other than HIV.

We know that it is not possible to take a protein from the 1.16 gm/ml mass and know from which component it originates. Let us then follow the same steps as Gallo and Montagnier. Take the mass of material banding at the 1.16 gm/ml, disrupt the proteins and electrophoretically position the proteins in a strip according to their molecular weights. Using this technique we are unable to state from which component of the 1.16 gm/ml band mass a protein on the strip derives. Next we incubate the proteins in the strip with patient sera and discover that some of the proteins react with antibodies present in the sera. Even if the antibody/antigen interaction is 100% specific such a reaction does permit us to define the origin of the proteins. Yet from such a reaction and without any proof that the antibodies specifically reacted, Montagnier and Gallo defined the origin of both the proteins and the antibodies as "HIV".

As mentioned, Montagnier found three proteins in the 1.16 gm/ml band which reacted with antibodies present in his patients' sera. These were p25, p80 and p45. Montagnier concluded that his patients were infected with a retrovirus which "contains a major p25 protein, similar in size to that of HTLV-I", but made no comment in regard to the p80 protein. Regarding p45 he wrote: "The 45K [p45] protein may be due to contamination of the virus by cellular actin".

In 1997 Montagnier said that the protein he detected in 1983 had a molecular weight of 43,000 and was actin. (The molecular weight of actin is neither 45,000 nor 43,000 but 41,000. However since Montagnier and Gallo determined the molecular weights of the proteins by their migration in an electrophoretic strip, and because the migration may be influenced by other factors, for example, by the protein's charge, it is possible that these slight differences in the molecular weight are simply the result of experimental variation).

When Gallo and his colleagues used the cellular proteins as antigens in the WB they reported: "The most prominent reactions were the antigens of the following molecular weights: 65,000, 60,000, 55,000, 41,000 and 24,000. Antigens with molecular weights of approximately 88,000, 80,000, 39,000, 32,000, 28,000 and 21,000 gave less prominent reactions…A large protein with a molecular weight of approximately 130,000 and a protein of 48,000 were also detected". In another experiment the "antigens from virus purified from the culture fluids", that is, the 1.16 gm/ml band, were incubated with different sera. They found an "Extensive" reaction of the AIDS patients sera with p24 and p41 and concluded: "these molecules are the major component of the virus-preparation. P24 and p41 may therefore be considered viral structural proteins…Furthermore, an antigen with a molecular weight of approximately 110,000 was detected in the virus preparation but was below limit of detection in the cells. Also, p39 was present in the virus preparation…Occasionally an additional set of antigens was recognised by a serum but their relation to the antigens described above is unclear".

Between 1983-87 the detection of antibodies in patient sera which reacted with p24 or p41 (Montagnier considered reaction with p24 and Gallo with p41 HIV specific) was considered proof that the patient was infected with HIV. In the same period of time it became obvious that a significant number of individuals at no risk of AIDS had antibodies which reacted with these proteins. Since 1987 most of the proteins which Gallo found to react either in the cell extracts or the 1.16 gm/ml band are now considered HIV proteins and laboratories require the presence of antibodies which react with more than one protein before the patient is considered infected with HIV. The number and identity of antibody/protein (Western blot) bands required vary from continent to continent, from country to country and even between and within laboratories in the same country. Thus it is possible for the same patient to be HIV seropositive in New York for example, but not in Africa or Australia.

Furthermore, for many years evidence exists which shows that p24 is not "HIV" specific123,124, p41 is the cellular protein actin,58,125,126 p32 is class II histocompatability DR protein126,127 and p120 / p160 are oligomers of p41.128

Even if proof exists that the "HIV" proteins do indeed belong to a unique exogenous retrovirus, it cannot be assumed that antibodies that react with them are diagnostic of "HIV" infection. To prove the specificity of the antibody tests it is mandatory to:

  1. test a large number of subjects with and without AIDS. The subjects without AIDS must not exclusively be healthy individuals (since they do not have high levels of antibodies, one would expect few if any reactions) but include the sick, such as patients with infectious diseases (other than those which are said to result from HIV infection), those receiving chemotherapy and those with auto-immune disorders;
  2. simultaneously (preferably on the same blood sample) perform tests for HIV isolation;
  3. compare the antibody test results with the results of HIV isolation, that is, use HIV as a gold standard for the antibody test.

To date nobody has published such studies using any definition of "HIV" isolation.

The inescapable conclusion is that the antibody/antigen reaction is not HIV specific and thus cannot be used to prove HIV isolation, no matter how isolation is defined.

 

MORE RECENT DEVELOPMENTS

By 1997 some of the best known HIV experts accepted that:

  1. "Purified" HIV contains cellular proteins, "some are over-represented in comparison to the relative amount in the cell membrane, whereas others appear to be absent", and that these proteins "serve as protective immunogens in vaccination experiments".
  2. HIV "used for biochemical and serological analyses or as immunogens is frequently prepared by centrifugation through sucrose gradients", but in none of the studies "the purity of the virus preparation has been verified". In other words, up till 1997 nobody has published electron micrographs of the 1.16 gm/ml band to prove that the "purified virus" contained nothing else but virus particles.

In that year, in Virology, two studies were published, one by a USA team, principal author Julian Bess, and the other by a Franco-German group, principal author Pablo Gluschankof, with the first electron micrographs of "purified HIV". While in the Gluschankof et al studies the EMs were from the 1.16 gm/ml band, in the Bess et al band they were from pooled bands. The authors of both studies claimed that their "purified" material contained some particles with the appearances of retroviruses and in fact were HIV particles. But they admitted that their material predominantly contained particles which were not retroviruses but "budding membrane particles frequently called microvesicles" or "mock virus". Indeed the caption to the Gluschankof et al electron micrograph reads, "Purified vesicles from infected H9 cells (a) and activated PBMC (b) supernatants", not purified HIV. In further experiments the supernatant from non-infected cultures was also banded in sucrose gradients. Both groups claimed that the banded material from these cultures contained only microvesicles, "mock virus" particles, but no HIV. Both the "HIV" particles and the mock-virus particles possessed membranes. In the USA study the "HIV-1 particles" were differentiated from the microvesicles "by the electron dense cores", whereas in the other study the "HIV" particles were "identified by the relatively homogenous diameter of about 110 nm, the dense cone-shaped core, and the "lateral bodies". However, in the arrowed particles which are said to be HIV it is difficult if not impossible to locate any which have cone-shaped cores or bilateral, "lateral bodies". In fact no particle in any study has the principle morphological characteristic of retrovirus, a diameter of 100-120 nM and surface spikes, knobs. In the Franco-German study the average "HIV" particle diameter is 136 nM and no particle had a diameter less than 120 nM. In the USA study the corresponding dimensions are 236 nM and 160 nM. In other words, the American "HIV" is twice the diameter of the European "HIV", and all other "HIV" particles. The US authors did not note or explain this discrepancy and "were much more focused on showing the mixture of particles in the preparations as opposed to their actual diameters". The diameter of the microvesicles "range in size from about 50 to 500 nm". Both the "HIV" and the "mock" virus particles contained RNA. The RNA of the latter had contained mRNA which is known to be rich in adenine and which, according to Gallo is specific to retroviral RNA. According to Gluschankof et al, "The vesicles contain large amounts of protein and nucleic acids which are unstructured and thus are transparent by electron microscopy", that is why many, but not all, appear "empty" by electron microscopy, while the nucleic acids in the "HIV" particles are structured and for this reason they appear to have an "electron dense cores". However, according to a leading retrovirologist, John Bader, the core density can be changed by external conditions, that is, the culture conditions. It is well known that a structural virus particle or virus-like particle can become "unstructured" in the presence of reducing agents. The possibility cannot be excluded then, that the apparent morphological differences between the two types of particles may be due to nothing more than the difference in the redox of the microenvironment in which they are assembled, released or both. It is significant that actin polymerisation (or actin/myosin interaction) "mediates HIV budding" and release. Evidence also exists that:

  1. As shown by Bess et al, uninfected cells exhibit buds which are no different from those in infected cells.
  2. There is an association between the redistribution of polymerised actin, myosin and other cellular proteins (glycoproteins) and many cellular processes including budding unrelated to release of retrovirus.
  3. Polymerisation of actin, actin-myosin interaction and cross-linking of polymers in general is regulated by the redox state, oxidation leading to interaction.
  4. Both AIDS patients and cultures derived from AIDS patients are subjected to oxidising agents. In fact, for the detection of "HIV" proteins and particles the cell cultures must be stimulated (treated with oxidising agents).
  5. In the presence of antioxidants no "HIV" phenomena can be observed.

The minimum absolutely necessary but not sufficient condition to claim that what are called "HIV-1 particles" are a retrovirus and not cellular microvesicles is to show that the sucrose density fractions obtained from the "infected" cells contain proteins which are not present in the same fractions obtained from non-infected cells. However, Bess et al have shown this is not the case. The only difference one can see in their SDS-polyacrylamide gel electrophoresis strips of "purified virus" and "mock virus" is quantitative, not qualitative. This quantitative difference may be due to many reasons including the fact that there were significant differences in the history and the mode of preparation of the non-infected and "infected" H9 cell cultures, in addition to the "infection".

A similar finding was reported by the same authors a few years earlier. However, while in both studies the proteins of molecular weight "near 42 kDa" (42,000) are labelled as "Actin" and "in the 30- to 40-kDa range" as "HLA DR", all the proteins with molecular weight higher than approximately 42,000 and lower than approximately 30,000 are left unlabelled in the earlier paper. In the 1997 study, three proteins of molecular weight lower than 30,000 are labelled as p24CA, p17MA, and p6/p7NC and are said to represent "major bands of viral proteins". However, also according to the authors, "these labels were added when one of the reviewers asked for them. He felt it would help orient readers when looking at the figure - the reviewer is correct. We did not determine the identities of the bands in this particular gel".

In their earlier study the researchers from the USA presented further evidence that the "viral proteins" were nothing more than cellular proteins. In their efforts to make an HIV vaccine they immunised macaques with, amongst other antigens, "mock virus", that is, sucrose density banded material from the supernatants of non-infected H9 cell cultures. After the initial immunisation the monkeys were given boosters at 4, 8 and 12 weeks. The animals were then challenged with "SIV" propagated either in H9 cells or macaque cells. When the WBs obtained after immunisation but before "SIV" challenge were compared with the WBs post-challenge, it was found that challenge with "SIV" propagated in macaque cells had some additional bands. However, the WBs obtained after the challenge with SIV propagated in H9 cells were identical with the WBs obtained after immunisation but before challenge. In other words, the protein immunogens in the "virus" were identical with the immunogens in the "mock virus". Since both the "mock virus" and "purified" virus contain the same proteins, then all the particles seen in the banded materials including what the authors of the 1997 Virology papers call "HIV" particles must be cellular vesicles. Since there is no proof that the banded, "purified virus", material contains retrovirus proteins and thus retrovirus particles then there can be no proof that any of the banded RNA is retroviral RNA. When such RNA (or its cDNA) is used as probes and primers for hybridisation and PCR studies, no matter what results are obtained, they cannot be considered proof for infection with a retrovirus, any retrovirus.

In the interview which Montagnier gave to Djamel Tahi he was asked why they did not publish an electron micrograph of the 1.16 gm/ml band to prove that the band represented "purified" virus, as they claimed. He replied that the reason for this was that even after "Roman effort" in their "purified" virus they could not see any particles with the "morphology typical of retroviruses. They were very different. Relatively different". When Montagnier was asked if Gallo isolated HIV he replied: "I do not believe so". If there were no retrovirus-like particles in Montagnier's "purified" virus, then obviously Montagnier and his colleagues could not claim to have isolated a specific exogenous retrovirus, HIV.

THE "HIV GENOME"

To claim that the stretch of RNA (cDNA) is the genome of a unique retroviral particle, HIV, the most basic requirement is proof for the existence of a unique molecular entity "HIV RNA" ("HIV DNA") that is, a unique fragment of RNA (DNA) identical in both composition and length in all infected individuals. The claim that a stretch of RNA (cDNA) is a unique molecular entity which constitutes the genome of a unique retrovirus can be accepted if and only if it is shown that the RNA belongs to particles with the morphological, physical and replicative characteristic of retroviral particles. Proof of this can only be obtained isolating the particles, that is, by obtaining them separate from everything else (purifying them). In 1984 both Gallo's and Montagnier's groups reported finding polyadenylated (adenine rich) RNA (poly(A)-RNA) in the 1.16 gm/ml band material obtained from "infected" cultures. The RNA was claimed to be HIV RNA that is, the HIV genome, and its complementary DNA, the HIV provirus. However,

  1. as mentioned, although Montagnier claimed his 1.16 gm/ml band contained pure "HIV"particles, according to him neither his band nor that of Gallo's contained any particles with "morphology typical of retroviruses";
  2. poly(A)-RNA is not specific to retroviruses. It can be found in all cells and even at the 1.16 gm/ml band obtained from "non-infected" cells;
  3. there is no proof for the existence of a unique molecular entity, "HIV-RNA" or "HIV-DNA", while the genomes of the most variable RNA viruses do not differ by more than 1%. The difference between the human and the chimpanzee genomes is no more than 2% while there is up to 40% variation between "HIV" genomes;
  4. in hybridization studies using the "HIV RNA" or cDNA, Gallo and since then many other researchers have been unable to prove the existence of the HIV genome in fresh lymphocytes from AIDS patients. In 1994 Gallo stated "We have never found HIV DNA in the tumour cells of KS…In fact we have never found HIV DNA in T-cells".
  1. All the claims of the existence of HIV in humans are based on polymerase chain reaction (PCR) studies using small fragments of the "HIV" genome as primers. However even researchers who believe that there is proof that the HIV primers and probes used in these studies are HIV accept that the specificity of this assay, using the antibody as a gold standard, varies between zero and 100 per cent. Even with the PCR nobody has reported the existence of the full "HIV" genome in the fresh lymphocytes of even a single AIDS patient.

Furthermore, despite the ample evidence to the contrary, for most retrovirologists the finding of a novel nucleic acid in a cell can be due to nothing else but an infectious agent. Half a century has passed since the Nobel Laureate Barbara McClintock discovered the phenomenon of transposition which can lead to the appearance of new genotypes and phenotypes. According to McClintock, the genome can be restructured not only by transposition but also by other means as well. In her Nobel lecture of 1983, she said, "rapid reorganisation of genomes may underline some species formation. Our present knowledge would suggest that these reorganizations originate from some "shock" that forced the genome to restructure itself in order to overcome a threat to its survival...Major genomic restructuring most certainly accompanied formation of new species". The "genomic shock" which leads to the origin of new species may be "either produced by accidents occurring within the cell itself, or imposed from without such as virus infections, species crosses, poisons of various sorts, or even altered surroundings such as those imposed by tissue culture. We are aware of some of the mishaps affecting DNA and also of their repair mechanisms, but many others could be difficult to recognize. Homeostatic adjustments to various accidents would be required if these accidents occur frequently. Many such mishaps and their adjustments would not be detected unless some event or observation directed attention to them...Unquestionably, we will emerge from this revolutionary period with modified views of components of cells and how they operate, but only however, to await the emergence of the next revolutionary phase that again will bring startling changes in concepts".

As we have mentioned elsewhere9,19 an exogenous retrovirus is only one possible explanation for the finding of novel nucleic acids in AIDS patients. Other explanations are:

  1. The genome of an endogenous retrovirus, that is, a stretch of RNA with a corresponding proviral DNA present in the cellular DNA of uninfected animals and which is passed from generation to generation vertically (from parents to offspring via the germ cell line) and which under certain conditions can be expressed and incorporated into retroviral particles.
  2. The genome of a retrovirus de novo assembled by genetic recombination and deletion of: (a) endogenous retroviral sequences or (b) retroviral and cellular sequences or (c) non-retroviral cellular genes.
  3. An RNA obtained by transposition, that is, by certain replicating DNA sequences (transposons) becoming inserted elsewhere in the genome, or by retroposition, that is, by particular RNA (retrotransposons) first being transcribed into DNA and then similarly being inserted into the genome. Retroposition can "use cellular mechanisms for passive retroposition, as well as retroelements containing reverse transcriptase". The retroelements may be retrovirus-like elements or nonviral elements. Not only can retroposition "shape and reshape the eukaryocytic genome in many different ways" but the nonviral retroelements may be similar to the retroviral elements.

A basic principle of molecular biology is that the primary sequence of RNA faithfully reflects the primary sequence of the DNA from which it is transcribed. However, in the 1980s RNA editing, "broadly defined as a process that changes the nucleotide sequences of an RNA molecule from that of the DNA template encoding it", was discovered. In the process a non-functional transcript can be re-tailored, producing a translatable mRNA, or modify an already functioning mRNA so that it generates a protein of altered amino acid sequences. Sometimes editing is so extensive that the majority of sequences in a mRNA are not genomically encoded but are generated post-transcriptionally producing the "paradoxical situation of a transcript that lacks sufficient complementarity to hybridize to its own gene!". According to Nancy Maizels and Alan Weiner from the Department of Molecular Biophysics and Biochemistry at Yale University, "the central dogma has survived hard times. The discovery of reverse transcriptase amended but did not violate the central dogma of how genes make proteins; introns qualified the conclusion that genes are necessarily collinear with the proteins they encode; somatic rearrangement of lymphocyte DNA called stability of eukaryotic genomes into doubt...and catalytic RNA challenged the pre-eminence of proteins and breathed new life into the ancient RNA world". However, the discovery of RNA editing "could come close to dealing it a mortal blow".

Thus the finding of novel RNAs in human cells, especially those of AIDS patients and those at risk, can no longer be regarded as incontrovertible proof that the RNA has been exogenously introduced by a putative HIV or any other infectious agents. That this may be the case has of late been accepted by Luc Montagnier. In a written testimony dated February 2nd 2000, to the US House of Representatives Committee on Government Reform, Subcommittee on National Security, Veterans Affairs and International Relations, in support of the work of his colleague, Howard B Urnovitz, (Montagnier is on the scientific advisory board of a publically traded biomedical company whose director is Urnovitz), Montagnier wrote: "I have reviewed Dr Urnovitz's published research and the testimony prepared for presentation to this Committee and strongly advise that future research on Gulf War Syndrome should include the study of the detected genetic material".

Urnovitz and his colleagues presented evidence of the existence, in Persian Gulf War veterans, of "novel", "nonviral" RNAs, "possibly induced by exposure to environmental genotoxins". They concluded: "The patterns of the occurrence of RPAs [polyribonucleotides] in the sera of GWVs [Gulf War Veterans] and healthy controls are sufficiently distinct to suggest possible future diagnostic applications…Our studies of patients with active multiple myeloma suggest that patients with individual chronic multifactorial diseases may have unique RPAs in their sera. Validated tests for such putative surrogate markers may aid in the diagnosis of such diseases or in the evaluation of responses to therapeutic modalities".

In the same year that Montagnier claimed HIV isolation, 1983, in a paper entitled "Expression of novel transposon-containing mRNAs in human T cells" researchers from the USA and Canada reported "Using an HERV-H LTR probe, 6 and 4.5 kb transcripts were detected by Northern blot analysis which were induced in normal peripheral T cells after treatment with phytohaemagglutin" (HERV human endogenous retrovirus). Phytohaemagglutin has been and continues to be used not only by Montagnier but by virtually every retrovirologist who claims proof for HIV isolation.

Since Montagnier agrees with Urnovitz that novel, nonviral RNAs appear in the Gulf War Veterans, then why should the existence of novel RNAs:

  1. In AIDS patients and those at risk be the genome of a retrovirus HIV and not the result of the many toxins including genotoxins to which they are exposed?
  2. In cultures containing tissues from AIDS patients be interpreted as HIV RNAs rather than the result of the many toxins including genotoxins to which both the patients and the cultures are exposed? Especially when both Montagnier and Gallo accept that HIV cannot be detected in cultures which are not treated with such toxins (oxidant agents) including PHA?

When hard pressed all the HIV experts will ultimately accept the non-specificity of retroviral-like particles, reverse transcription and antibody/antigen reactions. That this is the case is illustrated is exemplified by the fact that at the beginning of the AIDS era they were the first to report isolation of HIV from individuals at no risk of AIDS.166-168 In 1985 Weiss and his colleagues reported the isolation of a retrovirus from mitogenically stimulated T-cell cultures of two patients with common variable hypogammaglobulinaemia. This retrovirus "was clearly related to HTLV-III/LAV" (HIV); evidence included positive western blot with AIDS sera and hybridization with HIV probes.168 In 1984 Montagnier and his colleagues reported that "activated lymphocytes from a healthy blood donor were spontaneously releasing a virus similar to LAV1 in culture."169 With the method presently used for "HIV" isolation (reaction of p24 with proteins in culture) Schupbach and his associates using cultures of whole blood reported positive results in 49/60 (82%) of "presumably uninfected but serologically indeterminate" individuals and in 5/5 (100%) "seronegative blood donors".170

CONCLUSION

In 1983 Luc Montagnier and his colleagues and in 1984 Robert Gallo and his colleagues claimed to have proven the existence of HIV by purifying retroviral particles, that is, by obtaining a mass of particles isolated from everything else and showing that the particles are infectious. A critical analysis of their evidence shows that neither group presented proof of isolation of a novel retrovirus from AIDS patients. The phenomena they interpreted as HIV are all non-specific and were known to be so long before the AIDS era. In fact, given the origin of the cells and the culture conditions one would be expect to find all these phenomena even if the cultures are not infected with a retrovirus. In 1997 Montagnier himself stressed that to prove the existence of a unique retrovirus purification is absolutely necessary and admitted that he had not presented such proof, and in his view, neither had Gallo. Recognition of these facts may prove the first step in solving the problem of AIDS.

 

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151. Owens DK, Holodniy M, Garber AM, et al. (1996). Polymerase chain reaction for the diagnosis of HIV infection in adults. A meta-analysis with recommendations for clinical practice and study design. Annals of Internal Medicine 124:803-15.

152. McClintock B. (1984). The significance of responses of the genome to challenge. Science 226:792-801.

153. Weiner AM, Deininger PL, Efstratiadis A. (1986). Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annual Review of Biochemistry 55:631-661.

154. Leib-Mosch C, Brack-Werner R, Werner T, et al. (1990). Endogenous retroviral elements in human DNA. Cancer Research 50:5636s-5642s.

155. Covello PS, Gray MW. (1989). RNA editing in plant mitochondria. Nature 341:662-666.

156. Eisen H. (1988). RNA editing: Who's on first? Cell 53:331-332.

157. Lamond AI. (1988). RNA editing and the mysterious undercover genes of trypansomatid mitochondria. Trends in Biochemical Sciences 13:283-284.

158. Maizels N, Weiner N. (1988). In search of a template. Nature 334:469-470.

159. Montagnier L. (2000). Written testimony to the US House of Representatives. www.house.gov/reform/ns/hearings/subfolder/urnovitztest.htm

160. Urnovitz HB, Tuite JJ, Higashida JM, Murphy WH. (1999). RNAs in the sera of Persian Gulf War veterans have segments homologous to chromosome 22q11.2. Clinical Diagnostic Laboratory Immunology 6:330-5. http://cdli.asm.org/cgi/content/full/6/3/330

161. Kelleher CA, Wilkinson DA, Freeman JD, Mager DL, Gelfand EW. (1996). Expression of novel-transposon-containing mRNAs in human T cells. Journal of General Virology 77:1101-10.

162. Papadopulos-Eleopulos E, Hedland-Thomas B, Causer DA, Dufty AP. (1989). An alternative explanation for the radiosensitization of AIDS patients. International Journal of Radiation Oncology and Biological Physics 17:695-697.

163. Urnovitz HB. (2000). Statement for the Durban AIDS conference. . www.chronicillnet.org/AIDS/durban.htm

164. Ameisen J, Capron A. (1991). Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunology Today 12:102-105.

165. Urnovitz HB, Murphy WH. (1996). Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease. Clinical Microbiological Reviews 9:72-99.

 

166. Boussin, F.,Rey, F., Dormont, D. et al. 1988. Isolation of HIV in a seronegative demented patient without symptoms of immune deficiency. Cancer Detection and Prevention. 12:257-265.

167. Bayliss, G.J., Jesson, W.J., Evans, B.A. et al. 1989. Isolation of HIV-1 from small volumes of heparinized whole blood. AIDS 3:45-49.

168. Webster, A.D.B., Dalgleish, A.G., Beattie, R. et al. 1986. Isolation of retroviruses from two patients with "Common Variable" Hypogammaglobulinaemia. Lancet i:581-582.

169. Montagnier, Chermann, Barre-Sinossi et al. A new human lymphotropic retrovirus; characterization and possible role in lymphadenopathy and AIDS, in Human T-Cell Leukemia/Lymphoma Virus, edited by Robert C. Gallo, Cold Spring Harbor Laboratory, 1984, pages 363-379.

170. Schupbach, J., Jendis, J.B., Bron, C. et al. 1992. False-positive HIV-1 virus cultures using whole blood. AIDS 6:1545-1546.

 

References re introductory remarks

1. Padian NS, Shiboski SC, Glass SO, Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology 1997;146:350-357.

2. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, et al. Mother to Child Transmission of HIV and its Prevention with ATZ and Nevirapine. Perth: The Perth Group,2001. http://aidsmyth.addr.com/report/news/newperthpaper.htm

3. Papadopulos-Eleopulos E. Reappraisal of AIDS: Is the oxidation caused by the risk factors the primary cause? Medical Hypotheses 1988;25:151-162.

4. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Kaposi's sarcoma and HIV. Medical Hypotheses 1992;39:22-9.

5. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Oxidative stress, HIV and AIDS. Research in Immunology 1992;143:145-8.

6. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Hedland-Thomas B, Causer D, Page B. A critical analysis of the HIV-T4-cell-AIDS hypothesis. Genetica 1995;95:5-24.

7. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Bialy H. AIDS in Africa: Distinguishing fact and fiction. World Journal of Microbiology and Biotechnology 1995;11:135-143.

8. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Causer D. Factor VIII, HIV and AIDS in haemophiliacs: an analysis of their relationship. Genetica 1995;95:25-50.

9. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. The Isolation of HIV: Has it really been achieved? Continuum 1996;4:1s-24s.

10. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Virus Challenge. Continuum 1996;4:24-27.

11. Papadopulos-Eleopulos E, Turner VF, Causer DS, Papadimitriou JM. HIV transmission by donor semen. Lancet 1996;347:190-1.

12. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. HIV antibodies: Further questions and a plea for clarification. Current Medical Research and Opinion 1997;13:627-634.

13. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Page B. HIV antibody tests and viral load - more unanswered questions and a further plea for clarification. Current Medical Research and Opinion 1998;14:185-186.

14. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Alphonso H, Miller T. A critical analysis of the pharmacology of AZT and its use in AIDS. Current Medical Research and Opinion 1999;15 (Supplement 1):1s-45s.

15. Papadopulos-Eleopulos E, Turner VF. Analysis of mother-to-child transmission of HIV and the HIVNET 012 (Nevirapine) trial from Uganda, 2001 www.theperthgroup.com/aids 

16. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BA, Causer D, et al. Global voices on HIV/AIDS. Heterosexual transmission of HIV in Africa is no higher than anywhere else. British Medical Journal 2002;324:1035 /cgi/content/full/324/7344/1034#resp3

17. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, et al. High rates of HIV seropositivity in Africa-alternative explanation. in press International Journal of STD and AIDS 2003.

  Competing interests: None declared


Critical appraisal of evidence - does the BMJ have a vacancy? 25 April 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Critical appraisal of evidence - does the BMJ have a vacancy?

Wouldn't it be wonderful if the problem of ever-burgeoning nmbers of medical research publications could be tackled by someone with David Rasnick's amazing faculties of critical review?

Perhaps he should be snapped up by the BMJ to reject all the papers that are submitted for publication - this will certainly save a lot of trees.

It seems that nothing, no methodology, no data, no facts and no evidence, even if it has already passed muster through a peer-review process, will ever get his seal of approval. If the evidence seems sound, he will criticise the authors' motives in doing the study. A paper is either too short, or too long. A conclusion can be dismissed because it came from a cohort study, or because the study design is flawed. I can just imagine his rejection letters ..... "I am sorry to dismiss what you think is a significant finding, Dr Fleming. I don't care what you found, it cannot be true because your experiment was not really designed to show moulds can inhibit bacterial growth"

Before he gets too excited by the prospect of a new job, however, I must point out to David that there are bound to be problems. Firstly, his criticisms are usually completely without foundation, and secondly his critical faculties seem to mysteriously fail him when he is confronted by anything that might support his own idiosyncratic theories about HIV/AIDS.

Rasnick should realise that a lack of critical consistency and constant bias actually undermine his position, not strengthen it.

Competing interests:   None declared


Analysis of Flegg's references 5&6 26 April 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Analysis of Flegg's references 5&6

Dear Editor,

Peter Flegg uncritically accepts viral load as a measure of infectious HIV in spite of the documented problems with using it for that purpose (see my letters of March 7 and April 23, 2003). For example, he says that, "[viral load] levels are often extremely high during PHI [Flegg's reference(5), reference (1) below], and some individuals have seminal viral loads that consistently exceed plasma levels and are considered to be highly infectious hyperexcretors" even though they were either HIV negative at entry or HIV positive within 30 days of entry.

Apparently, Pilcher et al. were not aware of the pioneering study of Piatak et al. where high HIV viral load did not translate into infectious virus (2). Commenting on that study, Shepard et al. said that, "...the high level of plasma virus observed by Piatak et al. was about 99.9 per cent non-culturable, suggesting that it was either neutralized or defective... . [W]e question the longitudinal conclusions some of these investigators have drawn from cross- sectional data. The results presented are equally consistent with the conclusion that higher viraemia is a consequence of, rather than the proximate cause of, defective immune responses" (3).

Piatak et al. were unable to culture HIV from 53% of patients with viral loads ranging from 10,000 to over 2,000,000 copies of HIV RNA per ml of blood plasma (2). The authors said that, "Plasma virus levels determined by QC-PCR correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture. ... [And] For HIV-1 propagated in vitro, total virions have been reported to exceed culturable infectious units by factors of 10,000 to 10,000,000, ratios similar to those we observed in plasma."

With the Piatak et al. results in mind, I noticed that Pilcher et al. said that, "All subjects with primary HIV infection tested had positive PBMC HIV culture". However, they provided no data and it is unclear whether they cultured HIV from seminal plasma or only from blood plasma. If "positive PBMC HIV culture" meant the presence of p24 antigen in the supernatant, then (as I reported in the April 23, letter) the presence of transmissible HIV is in doubt because p24 antigen is not a reliable indicator of infectious HIV (or non-infectious HIV, for that matter).

Flegg goes on to say that, "Pilcher has also model[ed] transmission and estimates that during the peak viral shedding that is associated with PHI, transmission would be 20-fold higher than that during stable chronic infection. For individuals with peak seminal viral loads of log 8.85, the probability of transmission per act would be 1.0 (i.e. transmission would occur with every single exposure), dropping to 0.03 for individuals with levels of 5.43log, down to 0.0015 for levels of 3.75log [Flegg's reference (5), reference (1) below]. However, I could not find this information in the Pilcher et al. reference that Flegg cited (1). Perhaps he meant a different reference or I may have overlooked it, but I scanned the paper three times with no luck.

Flegg's last citation was to Chakraborty et al. who have "looked at HIV's infectiousness in 86 males and 24 females, and developed a model for calculating the probability of HIV transmission per heterosexual coital act [Flegg's reference (6), reference (4) below]. As levels of HIV-RNA rise in semen, probability of transmission increases (seminal level of log5 equating with probability of transmission of 1 per 100 episodes of intercourse)."

Chakraborty et al. begin by saying that, "Epidemiological and mathematical models have been developed to estimate the likelihood of HIV-1 transmission during a single episode of sexual intercourse. Such models are confounded by difficulty in collecting appropriate empirical data from discordant couples (when HIV-1 positive and negative people engage in sex) and from limitations in different kinds of estimation."

The "difficulty in collecting appropriate empirical data from discordant couples" is indeed a problem when the best controlled studies of discordant couples have failed to observe even a single HIV-negative sex partner becoming HIV-positive after years of observations (e.g. Padian et al. (5), where the observed efficiency of heterosexual transmission of HIV was zero).

Chakraborty et al. say that, "The probability of per-partner sexual transmission of HIV-1 has been examined in 11 different studies, whereas the per-sex-act probability of transmission has been reported in 13 studies. The probability of transmission of HIV-1 from male to female during an episode of intercourse has been examined in seven of these studies. Analysis of data from North America and European studies of heterosexual couples provide estimates of per-sex-act HIV-1 transmission of approximately 1 in 1000...".

Nevertheless, in 2001, the authors deemed it necessary to come up with yet another estimate because "the transmission probabilities presented [by the 7 studies in their Table 2] are so low that it becomes difficult to understand the magnitude of the HIV-1 pandemic, especially in developing countries. An alternative approach to explain the epidemic is development of mathematical models." Yet, the authors admit that, "The greatest limitation of this and other models lies in the tremendous difficulty in clinical validation."

The authors "assumed that the best predictor of infectiousness of the male partner is the cell-free virus measured in seminal plasma. It is not known whether HIV-1 is transmitted from cell free virus in the seminal plasma, or from cellular HIV-1." The unstated assumption, of course, is that HIV-1 is sexually transmitted in the first place. But of course, being that honest would never have gotten past the gatekeepers reviewing the manuscript.

Here is a summary of the stated and unstated assumptions that the authors used to construct their model: 1) HIV is sexually transmitted, 2) viral load is measuring the presence of HIV, 3) viral load measures the level of infectious HIV, 4) "the risk of HIV-1 transmission remains the same for each episode of intercourse..., although some have argued that exposure leads to some degree of immunity", 5) "that total non-synctium-inducing (NSI) HIV-1 RNA concentrations (x1) and CD4+CCR5 receptor cells (x2) were represented by a Pearson's type-1 distribution that could be transformed into a Beta distribution (subtracting the minimum value and divided by the range)", 6) "that 100% of the HIV-1 variants in the semen express the NSI phenotype, 7) "that HIV-1 variants which use CCR5 receptors (NSI isolates) are preferentially sexually transmitted", and 8) "The number of receptors for HIV-1 will also determine the efficiency of transmission".

Armed with these assumptions, an uncritical acceptance of the uncontrolled HIV-1 viral load data for seminal plasma from Chapel Hill, Seattle, and St. Gallen, plus additional subjects, and a considerable degree of mathematical hand-waving, the authors came up with an estimate of the probability of sexually transmitting HIV that is 10-fold greater (i.e. "1 per 100 episodes of intercourse") than the numerous estimates produced by others that they cite in Table 2 as being unable to explain "the magnitude of the HIV-1 pandemic, especially in developing countries". However, the authors make no comment as to whether their 10-fold higher estimate is sufficient to explain "the magnitude of the HIV-1 pandemic, especially in developing countries".

David Rasnick

References

1. Pilcher, C. D., Shugars, D. C., Fiscus, S. A., Miller, W. C., Menezes, P., Giner, J., Dean, B., Robertson, K., Hart, C. E., Lennox, J. L., Eron, J. J., Jr., and Hicks, C. B. (2001) HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health, Aids 15, 837-845

2. Piatak, M., Saag, M. S., Yang, L. C., Clark, S. J., Kappes, J. C., Luk, K.-C., Hahn, B. H., Shaw, G. M., and Lifson, J. D. (1993) High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR, Science 259, 1749-1754

3. Sheppard, H. W., Ascher, M. S., and Krowka, J. F. (1993) Viral burden and HIV disease, Nature 364, 291-292

4. Chakraborty, H., Sen, P. K., Helms, R. W., Vernazza, P. L., Fiscus, S. A., Eron, J. J., Patterson, B. K., Coombs, R. W., Krieger, J. N., and Cohen, M. S. (2001) Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model, Aids 15, 621-627

5. Padian, N. S., Shiboski, S. C., Glass, S. O., and Vittinghoff, E. (1997) Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study, Am J Epidemiol 146, 350-357

Competing interests:   None declared


The Piatak Study CONFIRMS the Link Between HIV and Disease AND Shows Antiretroviral Drug Efficacy... 28 April 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: The Piatak Study CONFIRMS the Link Between HIV and Disease AND Shows Antiretroviral Drug Efficacy...

M Piatak Jr and others have been cited above in support of alternative AIDS theories (yawn). As I have demonstrated with other researchers it is all too easy to establish that they do not support such ideas and that they have published numerous other papers which also confirm that they do not share the very beliefs attributed to them or their research.

for example:

> the pioneering study of Piatak et al. where high HIV viral load did not translate into infectious virus

The study in question was published in Science magazine(1). It found that HIV1-RNA levels were:

---
"significantly associated with disease stage and CD4+ T cell counts"
---

The strong association between HIV-1 RNA levels and both disease stage and CD4plus T cell counts was found to "confirm and extend work" by Coombs(2), Ho(2), Pantaleo(3), Schnittman(4), and Michael(5)

In spite of all this evidence, the (alleged) critic of this work is:

> Piatak et al. were unable to culture HIV from 53% of patients with viral loads ranging from 10,000 to over 2,000,000 copies of HIV RNA per ml of blood plasma

AND???

They were able to culture HIV from the other 46%. And even if they weren't, they weren't aiming to culture HIV. They were showing a correlation between HIV levels and disease. Which they did.

Piatak et al. also found that HIV levels:

---
"decreased by as much as 235-fold with resolution of primary infection or institution of antiretroviral therapy."
---

So aside from the association between disease and HIV levels the study found antiretroviral therapy highly effective. Now I'm sure someone will propose some obtuse and/or fallacious reason to discredit the study. Before doing so please explain why you called it 'pioneering', and why you cited it in support of the enduringly specious argument that there is no link between HIV and AIDS?

The evidence, once again, proves that their is little reason to doubt the existing rationale.

References:

(1) Piatak M Jr. Saag MS. Yang LC. Clark SJ. Kappes JC. Luk KC. Hahn BH. Shaw GM. Lifson JD. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.[comment]. [Journal Article] Science. 259(5102):1749-54, 1993 Mar 19. UI: 8096089 [Abstract]

(2) R. W. Coombs et al., ibid. 321, 1626 (1989); D. D. Ho, T. Moudgil, M. Alam, ibid., p. 1621.

(3) G. Pantaleo, C. Graziosi, A. S. Fauci, N. Engl. J. Med. 328, 327 (1993).

(4) S. M. Schnittman, J. J. Greenhouse, H. C. Lane, P. F. Pierce, A. S. Fauci, AIDS Res. Hum. Retroviruses 7, 361 (1991).

(5) N. L. Michael, M. Vahey, D. Burke, R. R. Redfield, J. Virol. 66, 310 (1992).

Competing interests:   None declared


Forget HIV/AIDS, is there sufficient evidence to prove that LIFE is sexually transmitted???????????? 29 April 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: Forget HIV/AIDS, is there sufficient evidence to prove that LIFE is sexually transmitted????????????

Studies examining the transmission of life appear to be rooted in an ASSUMPTION that life is sexually transmitted.

I hereby demand that you list for me all researchers who have shown unequivocally that it is. I will then, as done ad nauseam above, point to dubious procedural errors which may or may not pose any reason to doubt the conclusion of the study.

I will then present studies to prove my point, only to declare them invalid if some uppity student provides a link to the study and highlights that it didn't support my argument in the first place. Or I could point out that he/she mustn't have read the body of the article and clearly falsely assumed that any salient findings might be found in the Introduction, Findings and Conclusion.

So aside from 'rethinking' the HIV/AIDS issue, let's apply the same logic to the SPERM/EGG hypothesis. There's also no double-blind randomised controlled trial to prove that theory, and I'm sure the MEDICAL ESTABLISHMENT (whatever the hell that is) is propping up that theory for its own good also.

Tony

Competing interests:   None declared


Critical appraisal is essential 2 May 2003
Carl Williams,
layperson
TQ11 0LQ

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Re: Critical appraisal is essential

Dear Editor,  

It is both disappointing and frustrating to continue to witness the lack of civility and respect that certain contributors persistently display in their responses to fellow debaters.   

The recent contribution by Eleopulos et al, A critical examination of the evidence for the existence of HIV, illustrates above all else that there is still the need for serious critical debate of the contentious issues regarding HIV/AIDS.  Through critical appraisal of evidence and meaningful dialogue between scientists, researchers and clinicians, such as this forum makes possible, there is an opportunity to eradicate false impressions, to identify and make allowances for assumptions and to correct erroneous interpretations so that responsible public health recommendations can be made and safe and effective medical practices ensured.  Those who attempt to stifle such debate, or to debase it with inane and meaningless commentary do so out of fear because their own views lack intellectual propriety.  

A meaningful and productive debate can only be achieved if commentary is unfettered by personal attacks on contributors and if contributors themselves refrain from making deliberately obliquitous remarks that are intended to distract the reader from the original comments, rather than answer them.   

If the current understanding of HIV/AIDS is supported by an irrefutable mountain of evidence and research as some contributors to this debate would have us believe, then it is perfectly reasonable to expect that each and every one of Eleopulos's points should be fully considered and thoroughly confuted by both the researchers who support the accepted theory that HIV is a new exogenous retrovirus that is sexually transmitted and by those clinicians who make decisions daily by reference to that theory.  If such a confutation is not possible then surely it is time for the medical community to acknowledge this, rather than to continue to ignore the reality.  

In his rapid e-mail response to the allied BMJ article by Spurgeon, HIV denial, 18th February, Peter Flegg makes the following comments:

The standpoint of those in "HIV denial" has little in common with the scientific method, no matter how prettily "dressed up" they can make it appear. It is based firstly on an unbreakable conviction (faith?) that they are correct, so they ignore data that do not support their own hypothesis, champion data (irrespective of its provenance) that is supportive, misquote and misinterpret data to suit their own ends, and sometimes, as Brian Foley has demonstrated, knowingly mislead and lie. They are past masters at trying to pass off the prevailing scientific view on HIV as being rigidly entrenched in dogma, and like to view themselves as the modern-day Gallileos challenging the Orthodox Church. This flies in the face of what we have learned about HIV over the last two decades using and incorporating new scientific evidence and the systematic evaluation of data to reach a clear consensus.  

To adequately address the dissidents' arguments is difficult, since it can too easily become bogged down in detail and seemingly trivial points of order. Questions are seldom answered directly, but always replied to, with the intention of dragging the debate further off course and hopefully into a blind alley. Blatant misrepresentation of the evidence, dressed up to look scientifically plausible, can help persuade interested third parties with no scientific background as to the strength of their case.  

In another response by Peter Flegg, Do not be seduced by the sirens of dissidence, 21st February 2003 he goes on to say:  

Anand may not realise it, but rebuttals of points similar to Rasnick's have been made time and time again, but the dissidents ignore the message and refuse to behave like decent scientists should by modifying their views in the face of new evidence. Rasnick talks about problems with HIV testing, and quotes several sources, most of which are either not peer-reviewed or which are so old as to have been superceded by new data (of which he is no doubt aware but prepared to ignore). Of course HIV tests are not perfect, with 100% sensitivity and specificity, but recent assays approach this level and are some distance away from early assays used in the 1980s and often bedevilled by low (but unacceptable) false positivity rates.  

And lastly in a response entitled HIV/AIDS — there is no "debate" 3rd March 2003, Peter Flegg makes the following remarks:  

Whenever his claims are discounted, or a point by point rebuttal is given, instead of staying "on topic" and discussing these, he moves in a different direction. Good scientists are meant to accept new evidence and incorporate this into their hypotheses. The dissident approach is to ignore new evidence that is contradictory to their predetermined stance. After comprehensive rebuttal of any point of view, the dissident tactic is to quickly switch to a different topic. Then later, when no- one is looking, they can switch back to the original theme, hoping no-one will realise that these points were completely discredited on an earlier occasion.  

Having read all the responses to these two BMJ articles, it is difficult to understand how Peter Flegg can draw the conclusion that it is the so-called dissident commentators who are guilty of the anti-scientific approach he has leveled in his remarks above.   

I became interested in this web debate after reading Gisselquist et al's commentary in the International Journal of STD & AIDS 2003;14:148-161.  In that commentary the authors' note:  

"The post-1988 consensus that ascribed over 90% of adult HIV to heterosexual transmission and an insignificant proportion to unsafe injections was not at the time-or later-supported by calculations from evidence associating HIV with sexual behaviours. Instead, the numerical estimate seems to have been derived by a process of elimination."  

The authors go on to say:  

"Influential epidemiologic reviews published between 1987 and 1990 presented a variety of inferential arguments and hypothesis to support consensus estimates of sexual transmission."  

Later under the section: Why was evidence ignored? The authors' state:  

"It has been said that people often see what they wish to see."  

In Brewer et al's introduction to the same article pages 144-147, the authors make the following mention in their conclusion:  

"HIV is not transmitted by 'sex', but only by specific risky practices."   

The authors conclude by saying:  

"Dispassionate assessment of our conclusions admittedly depends on a willing suspension of disbelief, since the current paradigm is deeply embedded.  Counter arguments can (and will) be levelled at each of the anomalies noted, but the depth and breadth of concerns deserve fair scrutiny.  At issue in a re-evaluation of the heterosexual hypothesis are the profound implications for our interventive approach, and for the kind of social and financial commitments that must be made.  Finally Africans deserve scientifically sound information on the epidemiologic determinants of their calamitous AIDS epidemic."  

In looking at the research into the African AIDS epidemic I found that, in fact, large numbers of healthy, HIV positive individuals were living well into adulthood prior to 1973, at a time when HIV wasn't even thought to exist.  See my letter: Further comments on debate 18th March 2003 Rapid responses to: Canadian aboriginals in Vancouver face AIDS epidemic David Spurgeon, BMJ 2003; 326:  

More recently I became aware of research that is documented in Jaap Goudsmit's book 'Viral Sex'.  In the book Goudsmit discusses an epidemic of Pneumocystis carinni pneumonia in children that emerged just before World War II and lasted for about twenty years. It affected only children in their first year of life, only in continental Europe, but thousands of children died...Adults were affected but only sporadically".  According to Goudsmit, the cause of the PCP epidemic in children even before the AIDS era, was HIV.   

1 The epidemics appeared in "institutionalized, debilitated children…premature, malnourished infants".{Walzer, 1987 *2041}
2. Such epidemics occurred in widely separated hospitals of Eastern and Western Europe only in children, without parents or any other adult group being affected.
3. "In the laboratory the most striking observation was a hypergammaglobulinaemia.  This means an abnormally high level of antibodies—a sign of chronic infectious disease and a hallmark of AIDS in children".  Yet, "the 1950s disease was importantly different from paediatric AIDS as seen since the 1980s".
4."No children who recovered from early PCP (with or without CMV) died years later of other manifestations of immunodeficiency".
5. The epidemic stopped and the children cleared HIV without any treatment while in the AIDS era with tens of billions of dollars spent on treatment, HIV has not been cleared even from one single individual.{Goudsmit, 1997 *1330}

In conclusion  

If, as Jaap Goudsmit has documented, illnesses that are now considered to be proof of AIDS existed more than 50 years ago in central Europe in very large numbers and more importantly, if those diseases were caused by HIV, then the currently accepted notion that HIV is a new sexually transmitted exogenous retrovirus needs to be re-examined.   

The fact that those who survived (what is now considered to be an AIDS defining illness) did not go on to develop further manifestations of AIDS (without the modern diagnostic, monitoring and treatment for HIV that is believed to extend the lives of those diagnosed HIV positive), has deep significance with respect to the current treatment of HIV and the notion that being diagnosed HIV positive on its own leads inevitably to an early death.   

It is surely time that the medical community take seriously the points made by Eleopolus et al.  To my mind her comments, as do Brewer's and Gisselquist's send an important message to the medical community in general and to the HIV community in particular: that the accepted paradigm on which research is undertaken, treatment recommendations and clinical decisions made, needs to be urgently reappraised.  

Yours  

Carl Williams    

Competing interests:   None declared


Let's critically analyse data instead of merely reading and quoting abstracts 1 May 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: Let's critically analyse data instead of merely reading and quoting abstracts

Let's critically analyse data instead of merely reading and quoting abstracts

In his rapid response "Use of CONDOMS for heterosexual intercourse is HIGHLY EFFECTIVE IN PREVENTING HIV TRANSMISSION......" (17th April 2003) Tony misleads again by his use of the word "found" in his statement: "Perhaps the results of de Vincenzi's longitudinal study published in the New England Journal of Medicine (1) mean that she 'found' that: "Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV." If Tony had read not only the abstract of the de Vincenzi study but had also critically analysed her data he certainly would not have suggested that de Vincenzi "found".

For de Vincenzi (1) to make the above claim, she had first to prove that heterosexual (vaginal) transmission of HIV takes place. She did not.

• In her study, 65% of the index cases were drug users. This means that an unknown number of their partners may have also been drug users. This was acknowledged by Padian in her studies.
• 16.5% of the male index partners were bisexuals. This means that an unknown number of the non-index male partners may have also been bisexual.
• 11 of the 256 couples refused to answer questions about sexual behaviour although the negative partners agreed to follow-up testing. Of the remaining couples, 17.5% were practising anal intercourse at entry into the study and 12.5% during follow-up.

Taking these things into consideration, finding of a positive antibody test in a negative partner during followup cannot be considered as proof for HIV transmission through vaginal intercourse. Although, de Vincenzi did not specify how many of the individuals who seroconverted were practising anal intercourse, she did point out that the seroconversion may have taken place either through "vaginal or anal sex". She wrote: "Twelve initially uninfected partners seroconverted among the 121 couples using condoms inconsistently for vaginal or anal sex…".

According to Brody (2): " 'The problem of subjects' lying (often euphemistically termed "social desirability responding") about engaging in anal intercourse and intravenous drug use plagues most studies of behavioral risk factors for the transmission of HIV, and the study by de Vincenzi and colleagues is no exception. How was the absence of homosexual contact verified? How was the absence of anal intercourse among the women verified? If only 4 men and 6 women among the 121 couples inconsistently using condoms lied when they denied engaging in anal intercourse (or misreported the facts for other reasons), there would be no cases attributable to vaginal intercourse without a condom. At least this much lying should be expected."

Regarding the claim that condoms prevent transmission:

• In the de Vincenzi study there was a significant loss (19.5%) to followup.
• The study was conducted in several European countries and HIV testing was performed "in the laboratories of the participating centers". Since each country uses different criteria for the antibody test, the test was not standardised (www.virusmyth.com/aids/data/vtwbtests.htm).
• The testing was not performed blind.
• Compared to the consistent condom users, Brody pointed out, "The inconsistent condom users in the study by de Vincenzi and colleagues had more than twice the prevalence of anal intercourse at follow-up and also had more sexual contacts."

According to US researchers (3): "De Vincenzi (Aug. 11 issue)concludes that consistent use of condoms is highly effective in preventing heterosexual transmission of the human immunodeficiency virus (HIV). However, the data analysis is flawed. First, the use of person- years as the unit of comparison for seroconversion rates does not take into account the difference between consistent and inconsistent users of condoms in the frequency of sexual contact. The author reports that the median frequency of sexual contact among the latter was twice that among the former. Once this is accounted for, the seroconversion rate for inconsistent users is 2.5 per 100 person-years (95 percent confidence interval, 1.2 to 5.8), which is not significantly different from the rate of 0 for consistent users (95 percent confidence interval, 0 to 1.5 per 100 person-years).

Second, the author does not adequately define the temporal pattern of seroconversion among inconsistent users of condoms. Those who seroconverted within the first three months of the study were most likely infected before enrollment. Thus, the seroconversion rate for the group of inconsistent condom users may be even lower."

Again, Tony misleads with his statement regarding heterosexual transmission of HIV: "Whether it is approximately 30%, approximately 90%, or approximately something in between, this would (as supported by de Vincenzi) still be a lot more than precisely zero.", since such a statement implies that Gisselquist claims a lower limit of approximately 30% which is not the case. Gisselquist (3) wrote "There are many considerations — focused on specific parameters — that suggest that the estimates we present are too high or too low" as we pointed out in our rapid response "Assumptions and opinions do not prove heterosexual transmission of HIV" (15th April 2003). Note, "too high" is not the same as "approximately".

References

1. de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med. 1994 Aug 11;331(6):341-6.

2. Brody S. Heterosexual Transmission of HIV. N Engl J Med 1994; 331:1717-1719, Dec 22, 1994.

3. Ambati J., Ambati B. K., Rao A. M. Heterosexual Transmission of HIV. N Engl J Med 1994; 331:1717-1719, Dec 22, 1994.

4. Gisselquist D, Potterat JJ. Heterosexual transmission of HIV in Africa: an empiric estimate. Int J STD AIDS. 2003 Mar;14(3):162-73

Competing interests:   None declared


Does sexual intercourse result in pregnancy? 2 May 2003
Peter J Flegg,
Consultanat Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Does sexual intercourse result in pregnancy?

Like your correspondent, Tony Floyd, I am also beginning to entertain doubts about a lot of things, having spent some time appreciating the scientific logic of the HIV dissidents and their "evidence" that HIV is not spread sexually.

I realise that one of the main cornerstones in their argument is the finding by Nancy Padian that HIV transmission occurred infrequently in heterosexual couples (the dissidents conveniently ignore other studies showing higher transmission rates, or refuse to acknowledge the reasons as to why the rate of transmission was low in Padian's study).

I wondered if I could apply the same infallible logic to the thorny issue of whether pregnancy is the result of sexual intercourse. After all, they are not very well correlated temporally, not everyone who has sex becomes pregnant, and there are many cases where pregnancy has occurred when the woman concerned has categorically denied having had sex! These facts are highly suggestive that the outcome event and the putative risk activity are completely unrelated.

I eventually found "proof" for my theory when I read of a study looking at pregnancy rates in heterosexual couples over a study period of 250 couple-years duration(1). This study found very few pregnancy events, and indeed in one part of the study no pregnancies were recorded at all. This reinforces my pre-existing conviction that my theory is right.

However, I am ignoring some relevant facts. These will obviously be important in diminishing the chances of observing a pregnancy event, but I will conveniently choose to ignore them, since as a true neodissident scientist, I will be sure not to let facts get in the way of my opinions.

(1) To be eligible for the study, couples had to have been engaged in a long term sexual relationship that had already failed to be associated with a pregnancy event.

(2) Nothing was known about the couples underlying fertility.

(3) Before, and during the study at 6 monthly intervals, couples were encouraged to practice safe sex and use condoms.

(4) 75% of couples used condoms in the study.

(5) 15% abstained from sex entirely.

I know all of these things would significantly lessen the chance of pregnancy if indeed it is sexually "transmitted", but none of them can shake my conviction that this study above all others provides conclusive proof that sex cannot result in pregnancy.

References (with apologies to Nancy Padian) (1) Padian N, Shiboski S, Vittinghoff E, Glass S. Heterosexual transmission of pregnancy: Results from a ten year study. Am J Epidemiol 146:350-357, 1997

PS - substitute HIV for pregnancy to get the original Padian reference.

Competing interests:   None declared


Time to Put Padian to Bed Before Moving on to Other Authors Who Have Been Misrepresented 4 May 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Time to Put Padian to Bed Before Moving on to Other Authors Who Have Been Misrepresented

The Padian paper(1) is, it seems, just as effective for disproving the idea that life is sexually transmitted as it is for claims that HIV isn't(2).

From a response dated 24th March 2003:

>"The Padian study is considered to be the best study of its type in which the author vigorously strived to prove heterosexual transmission."

Rubbish.

The Padian paper (available on line here) does not strive to vigorously prove heterosexual transmission. That goal is not stated ANYWHERE in the abstract or in the full text version. The authors wished to 'examine' rates, although I doubt they 'vigorously' discouraged condom use or were disappointed about the very low (less than 3%) occurrence of other STD's in the group before enrolling, or the decrease in anal sex and increase in condom use etc. etc.

For other reasons already enunciated ad nauseam above, the Padian paper provides no good reason to doubt heterosexual transmission. Nor does it prove heterosexual transmission, nor does it prove or disprove that life itself is sexually transmitted. It was designed to do none of these.

From another response:

>"It has been said that people often see what they wish to see."

Precisely!

References:

(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15. [Abstract] Does sexual intercourse result in pregnancy?

(2) Flegg PJ. Does sexual intercourse result in pregnancy? BMJ Rapid Response. 2 May 2003

Competing interests:   None declared


Yes. It is about time to move on. 5 May 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: Yes. It is about time to move on.

Yes. It is about time to move on

In his rapid response "Time to Put Padian to Bed Before Moving on to Other Authors Who Have Been Misrepresented" (4 May 2003), Tony Floyd again misleads. He wrote: "The Padian paper (available on line here) does not strive to vigorously prove heterosexual transmission. That goal is not stated ANYWHERE in the abstract or in the full text version." Note that "Padian paper" is NOT the same as "Padian study". In her study, Padian published several papers (not only just one paper) and presented her data at several meetings. She did not have to state that she did "strive to vigorously prove heterosexual transmission". It is obvious from her lengthy study that her aim was to prove heterosexual transmission. Tony wrote: "Nor does it prove heterosexual transmission, nor does it prove or disprove that life itself is sexually transmitted. It was designed to do none of these." We are glad that Tony agrees with us that the Padian study does not prove heterosexual transmission. If it was not designed to prove heterosexual transmission then what was Padian doing in what she herself called "the largest and longest study of heterosexual transmission of HIV in the United States"(1)?

In his rapid response "Does Sexual intercourse result in pregnancy?" (2 May 2003), Peter Flegg wrote: "I realise that one of the main cornerstones in their argument is the finding by Nancy Padian that HIV transmission occurred infrequently in heterosexual couples (the dissidents conveniently ignore other studies showing higher transmission rates, or refuse to acknowledge the reasons as to why the rate of transmission was low in Padian's study)." As Tony acknowledges, the Padian study did not prove infrequent or low heterosexual transmission. It does not "prove heterosexual transmission".

We agree to its "time to put Padian to bed" and for Tony Floyd and Peter Flegg to draw our attention to "other studies showing higher transmission rates". However, let us draw their attention once again to the fact that for such studies to be accepted as scientific proof for heterosexual transmission they must satisfy the following (as pointed out in our rapid response, 24 March 2003): • Be prospective • Use tests which have been proven to be specific • Have a statistically meaningful population • The results must be statistically significant and must exclude other possible routes of infection

References (1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997.

Competing interests:   None declared


No Matter How You Twist Mr Gisselquist, He Does Not Support Alternative AIDS Theories. 7 May 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: No Matter How You Twist Mr Gisselquist, He Does Not Support Alternative AIDS Theories.

Responding to some of the comments above:

>Again, Tony misleads with his statement regarding heterosexual transmission of HIV

au contraire.

In fact you have mislead (again) regarding heterosexual transmission of HIV:

>"Whether it is approximately 30%, approximately 90%, or approximately something in between, this would (as supported by de Vincenzi) still be a lot more than precisely zero.", since such a statement implies that Gisselquist claims a lower limit of approximately 30% which is not the case.

I in no way implied that Gisselquist himself suggested a 'lower limit' of approximately 30%. And how would it matter if he did? In fact the ranges that he gave were unequivocally clear from the quote I have already given above(1):

---
"For more than a decade, most experts have assumed that more than 90% of HIV in African adults results from heterosexual transmission. In this exercise, we show how data from studies of risk factors for HIV can be used to estimate the proportion from sexual transmission, and we present our estimates. Calculating two ways from available data, our two point estimates - we do not estimate confidence intervals - are that 25-29% of HIV incidence in African women and 30-35% in men is attributable to sexual transmission"
---

Both his estimate of approximatley 30% heterosexual transmission of HIV and that of 'most experts' remain very much distant from any claims that it is precisely zero.

Hence I repeat my question from April 5th: Why has Gisselquist been cited to support claims that HIV isn't sexually transmitted? He has published work to indicate that he does not support any such alternative theories.

Here's another fine example (referring to the Padian study):

"It is obvious from her lengthy study that her aim was to prove heterosexual transmission"

Obvious? Yet she failed to state that anywhere.

In fact she was examining ways to prevent transmission in the same study group(2):

---
"Couple counseling in combination with social support appears to be an effective means to promote and sustain behavior change among HIV-infected individuals and their heterosexual partners."
---

If anything it is obvious that she didn't want any seroconversions.

Gisselquist and Padian continue to be falsely referenced in support of alternative AIDS theories.

References:

(1) Gisselquist D, Potterat JJ. Heterosexual transmission of HIV in Africa: an empiric estimate. Int J STD AIDS. 2003 Mar;14(3):162-73. PMID: 12665438 [Abstract]

(2) Padian NS, O'Brien TR, Chang Y, Glass S, Francis DP. Prevention of heterosexual transmission of human immunodeficiency virus through couple counseling. J Acquir Immune Defic Syndr. 1993 Sep;6(9):1043-8. PMID: 8340895 [Abstract]

Competing interests:   None declared


Your argument has more holes in it than something full of holes used for comparative purposes. 8 May 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Your argument has more holes in it than something full of holes used for comparative purposes.

Taking a closer look at two articles referenced above:

>the 'HIV' proteins have been and still are obtained from particulate material which consists overwhelmingly of cellular fragments in which are interspersed a small number of particles whose morphology more resembles that of retrovirus particles but none of which have all the structural characteristics attributed to HIV or even to retrovirus particles.26 27 ...In other words, the antigens in the antibody tests could be nothing more than cellular proteins

The first reference given is from Bess and colleagues' 1997 paper(1). It does discuss the problem of 'nonvirion-associated cellular proteins'. It does not suggest that there was any doubt as to which proteins were from the virus and which were picked up from the host T-cell as the virus budded.

Furthermore Bess has continued to work on vaccines targeting HIV(2):

---
"By exploiting the intrinsic chemistry of retroviruses, we have developed a novel method for generating whole inactivated virion vaccine immunogens"
---

Why would he do this if his earlier work on microvesicles as 'contaminating proteins' gave cause to doubt HIV testing in general? Perhaps it didn't.

Does the other author cited (Gluschankof) provide any reason to doubt the existence of HIV or the validity of HIV testing? Or did he also entitle a paper in such a way that it would later be misused to support extraordinary claims?

His 2001 paper(3) states:

---
"The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection. "
---

Those encouraging 'critical analysis' should also encourage accurate analysis. There is no evidence that these researchers (or their work) add credence to alternative AIDS theories.

References:

(1) Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virology. 1997 Mar 31;230(1):134-44. PMID: 9126269 [Abstract]

(2) Chertova E, Crise BJ, Morcock DR, Bess JW Jr, Henderson LE, Lifson JD. Sites, mechanism of action and lack of reversibility of primate lentivirus inactivation by preferential covalent modification of virion internal proteins. Curr Mol Med. 2003 May;3(3):265-72. PMID: 12699362 [Abstract]

(3) Gondois-Rey F, Biancotto A, Pion M, Chenine AL, Gluschankof P, Horejsi V, Tamalet C, Vigne R, Hirsch I. Production of HIV-1 by resting memory T lymphocytes. AIDS. 2001 Oct 19;15(15):1931-40. PMID: 11600820 [Abstract]

Competing interests:   None declared


The politics of AIDS in South Africa 8 May 2003
Gordon Stewart,
Emeritus Professor of Public Health
University of Glasgow

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Re: The politics of AIDS in South Africa

In this article, Fassin and Scheider allege that President Mbeki has "Formally distanced himself from the AIDS dissidents". Having served at the President's invitation as a neutral member of his Panel since 1999, I have to say that I have received no such intimation. The questions which he addressed to this Panel, in my view correctly, remain unanswered. The controversy to which Fassin and Schneider refer would be quickly settled if these questions were debated openly in the light of proposals and investigations submitted by experts on the Panel, perticularly with regard to the reliability of the surrogate tests and definitions used in sub-Saharan Africa for surveillance and diagnosis of HIV/AIDS.

In this context, I should say also that I do not favour restrictions in the judicious use of approved anti-microbial drugs for palliative purposes in individual patients with symptomatic AIDS. If doctors care to prescribe these drugs in the best interests of their patients and on their own responsibility, they should be free to do so but they should be informed of the scheduled risks which should be independently monitored. Any commercial or other conflict of interest should be declared. I have none.

Gordon Stewart, Emeritus Professor of Public Health, University of Glasgow, UK.

Competing interests:   None declared


Re: The politics of AIDS in South Africa 14 May 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Re: The politics of AIDS in South Africa

Gordon Stewart challenges Fassin and Scheider's assertion that President Mbeki has distanced himself from the AIDS dissidents (http://bmj.com/cgi/eletters/326/7387/495#32045).

Stewart says "Having served at the President's invitation as a neutral member of his Panel since 1999, I have to say that I have received no such intimation." Does this omission really constitute evidence as to what Mbeki's intentions might be? As a "neutral member" (whatever that means), why should Gordon Stewart expect to be personally informed of Mbeki's decisions?

It is quite clear that Mbeki has tired of dissidents using the designation "Member of the Presidential AIDS Panel". A year ago it is reported that Joel Netshitenzhe, a South African Government spokesman, confirmed that there had been discussion about getting the dissidents to stop misusing Mbeki's name. He has stated that dissidents were being told that they couldn't sign themselves as if they represent the view of the entire panel (1). It is also stated in this same report that Mbeki had decided to cut informal contact with the dissidents and communicate with them only when the advisory panel meets. These statements add weight to the claim by Fassin and Scheider that Mbeki has distanced himself from the AIDS dissidents.

However, it is clear that the dissidents are still continuing to use the epithet "Member of the Presidential AIDS Advisory Panel" whenever it suits them, despite Mbeki's objections (2). I must admit, it is a grand and eye-catching title, and presumably the dissidents feel it confers considerable debating prestige.

The question has also been raised as to whether the Presidential Panel is defunct. David Rasnick has categorically stated that it is not. Perhaps he, or Gordon Stewart, would be so kind as to tell us on what occasions it has met since July 2000, or when the next meeting is to be held? Surely it is quite safe to say this particular Norwegian Blue Parrot, er, ...sorry, Panel, has ceased to be?

(1) Makhanya, Mondli. Mbeki shuns Aids dissidents; Scientists ordered to stop using President's name. Sunday Times (Johannesburg) - Sunday 21 April 2002.

(2) Turner, Valender. AIDS is not a party political problem. Mail and Guardian (SA) 25 April 2003.

Competing interests:   None declared


Mbeki's AIDS Panel still active 15 May 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Mbeki's AIDS Panel still active

Dear Editor,

Peter Flegg cites two South African newspapers as evidence that Mbeki has distanced himself from the AIDS dissidents and that his AIDS Panel is defunct. He says that, "It is quite clear that Mbeki has tired of dissidents using the designation "Member of the Presidential AIDS Panel". He also asks, "on what occasions has [the Panel] met since July 2000, or when the next meeting is to be held?

Flegg failed to cite the Health Minister saying that, "Rasnick may sign himself as presidential panelist because that is what he is" (1).

Flegg also failed to cite the government's response to the newspaper reports that he cited. Mbeki's spokesman, Bheki Khumalo, replied that, "no decision had been taken to disband the panel or to instruct its members to refrain from using Mbeki's name" (2).

To this day, none of the members of Mbeki's AIDS Advisory Panel has been instructed by the government to stop identifying himself or herself as a member of the panel. We have also not been informed that the AIDS Advisory Panel has been disbanded.

In welcoming the international group of AIDS experts to the first Panel meeting in May 2000, Mbeki said that we were to advise the SA government as individuals and not as representatives of any organizations. That point was made clear at subsequent meetings.

The government of SA continues to seek our services. October 2001, Harvey Bialy, Sam Mhlongo and I participated in a meeting with other SA members of the AIDS Advisory Panel to develop protocols for future experiments to determine the accuracy of the HIV antibody test. Roberto Giraldo, also a member of the AIDS Advisory Panel, just returned from SA last Sunday after advising the government on nutrition and AIDS. Just months before, at the request of the Health Minister, he participated in a large meeting on nutrition and AIDS.

The interim report of the AIDS Advisory Panel that was published March 2001, recommended ten experiments and studies that address hotly disputed questions about the contagious/HIV hypothesis of AIDS, the validity of the HIV antibody tests, and the safety and efficacy of the anti-HIV drugs (3). All ten have been approved by the government and the funds allocated. Members of the AIDS Advisory Panel will conduct and oversee these experiments and studies.

This is strong evidence that the Presidential AIDS Advisory Panel continues to be of service to the people and government of SA.

David Rasnick, PhD Member of the Presidential AIDS Advisory Panel

1) No Stopping This AIDS Dissident, Business Day, Johannesburg, September 14, 2001.

2) HIV/Aids Dissidents Cling to Their Links With Mbeki, Business Day, Johannesburg, April 26, 2002.

3) Secretariat for Thabo Mbeki (March 2001), Presidential AIDS Advisory Panel Report, Johannesburg.

Competing interests:   None declared


"If it makes you feel good....." 17 May 2003
Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital,
UK, FY3 8NR

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I thank David Rasnick for updating me on the activities of members of the Presidential AIDS Panel. I hope that progress on the outstanding questions can be properly addressed. If my memory serves me correctly, was the report on the validity of the HIV antibody tests not published recently?

I doubt, however, whether individual visits from members (Giraldo) to South Africa count as "meetings of the Advisory Panel".

What is clear from browsing South African news reports on the web is that there has been continuing and increasing disapproval of Mbeki's flirtation with dissidents such as Rasnick, particularly since the Government seemingly conceded the reality of a link between HIV and AIDS, and the value of therapy in the scenario of mother to child transmission (even if they have been dragged kicking and screaming into this acceptance by the high court).

Rasnick says that the Health Minister has sanctioned his use of the term Presidential Panelist (1). The report quotes the minister as saying "If it makes him (Rasnick) feel good to sign himself that way then he can do it. I can't stop him." This hardly sounds like an unqualified endorsement to me. The report also states "Rasnick has been reportedly irritating government health officials with a flood of letters, proclaiming that HIV was harmless and not contagious".

More recent news reports reveal the continuing unease about the use of the title "Presidential Panellist" in dissident communications (2). Business Day records the following: "(the)State's about-turn on drugs raises questions over his (Mbeki's) relationship with David Rasnick and Peter Duesburg, who question the link between HIV and AIDS. There have been discussions among senior members of government aimed at getting the socalled HIV/AIDS dissidents to stop misusing President Thabo Mbeki's name. Presidential spokesman Bheki Khumalo said that the matter had been discussed at some levels of government "but these discussions did not involve the President"."

An outsider trying to make sense of the situation might well conclude that the South African Government doesn't know what to think or say about the HIV situation. For that matter, I doubt if any insider really knows either. Rasnick may not have recieved direct instructions from the powers that be on use of his "title", but I wonder if this is a result of the SA Government's cognitive paralysis on the issue, or fear that any positive action might provides Mbeki's critics with a propaganda coup. After all, was it not Rasnick himself who said there was a CIA-led conspiracy to target Mbeki, with "millions of US dollars being spent to monitor and neutralise" him?(3)

1) No Stopping This AIDS Dissident. Business Day, Johannesburg, September 14, 2001.

2) Officials Urge Aids Dissidents to Stop Misusing Mbeki's Name. Business Day, Johannesburg, April 22, 2002.

3)Dissident Supports "Plot Against Mbeki" Theory. Mail and Guardian, Johannesburg, May 10, 2001.

Competing interests:   None declared


Mbeki's AIDS Advisory Panel: what happened 19 May 2003
David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583

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Re: Mbeki's AIDS Advisory Panel: what happened

Dear Editor,

I have an advantage over Peter Flegg in that I know what actually happened during the Presidential AIDS Advisory Panel meetings of 2000. While I and the other minority members of the panel were active contributors, the mainstream members, on the other hand, were reluctant participants. It was clear that the members from the US CDC and the NIH had been ordered to attend the panel meetings. They certainly didn't want to be there. Just as the first meeting got underway, three well-dressed black men with stern faces joined the panel. None of us know who they were. This unexplained intrusion angered a number of the South African members on the panel. They demanded to know who those three were, why they were there and who sent them. Finally, someone from the Health Minister's office stepped forward to say that the Clinton administration had sent them to observe the proceedings. Beyond giving their names and affiliations, I don't recall any of the three saying another word.

The May 2000 meeting didn't accomplish much because the mainstream members objected to the presentation of any information. This became clear when Peter Duesberg tried to show slides with data. Immediately, someone from the NIH, as I recall, objected. Inexplicably, the moderator allowed the mainstream to veto the presentation of any material. So, we just went around the table saying in a few minutes whatever each of us had to say. When Luc Montagnier's turn came, he tried to make a presentation of data, but Duesberg reminded the moderator that he had not been allowed to present data, at which point Montagnier sat down. Later during the meeting, Montagnier fell asleep in his chair. It became very clear that the mainstream's strategy was to say as little as possible, do as little as possible, and let the whole thing blow away.

A second meeting of the panel was scheduled for July 2000. To prepare for that meeting, the government had set up a secure website where the members of the panel could debate issues, exchange information and come up with an agenda for the July meeting. However, the second meeting of Mbeki's AIDS Advisory Panel presented an embarrassing problem for the mainstream because the International AIDS Conference would be taking place in Durban South Africa also in July. Instead of taking advantage of the extraordinary opportunity to make their case for the contagious/ HIV hypothesis of AIDS directly to the President of South Africa, his ministers and other government officials, the mainstream members set up their own secret internet system, which led to the "Durban Declaration" (1). The Durban Declaration was published in Nature in 2000 and was signed by "over 5,000 people, including Nobel prizewinners" and reads like a catechism of HIV-AIDS dogma. The Durban Declaration was intended to neutralize the high profile questioning of AIDS dogma by the President's AIDS panel. (You can find among other things an extensive rebuttal of the assertions made in the Durban Declaration in the June 2003 issue of the Journal of Biosciences (2).)

When the Presidential AIDS Advisory Panel met in July, the Health Minister and the health directorate castigated the mainstream members for boycotting the internet debate and discussions that had been set up by the government. The minister said the government was furious about the secret internet effort by the mainstream members to undermine the work of Mbeki's AIDS Advisory Panel. Due to the lack of good faith on the part of the mainstream members and their participation in the Durban Declaration, the government agreed to the minority (dissident) members' request for formal presentations of arguments and evidence for and against the contagious/HIV hypothesis at the July meeting. This forced the mainstream to put forward at least a token effort of making their case. That was the first and last time I'm aware of that the mainstream members contributed much of anything to Mbeki's AIDS Advisory Panel's deliberations. Therefore, it is little wonder that the government has not gone to the expense and trouble of setting up a third full meeting of the panel given this history. From time to time, those members of the panel who participated in good faith continue to provide help and advice to the government on AIDS.

1. The Durban Declaration. (2000) The Durban Declaration, Nature 406, 15-16

2. Duesberg, P., Koehnlein, C., and Rasnick, D. (2003) The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral chemotherapy and malnutrition, J. Biosci. 28, 383-412

Competing interests:   None declared


Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity? 22 May 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity?

Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity?

In his rapid response "Your argument has more holes in it than something full of holes used for comparative purposes" (8 May 2003), Tony Floyd wrote "Those encouraging 'critical analysis' should also encourage accurate analysis". We go further by saying that those who encourage 'accurate analysis' should read a paper in its entirety when presenting their "accurate analysis" rather than merely quoting from the abstract and then drawing conclusions which may not be supported by the data in the paper. If Tony had read the 1997 paper by Bess et al (1), by looking at figure 1 in the paper where the electrophoretic patterns of proteins in "purified HIV" were compared with those in "mock virus", he may have come to the same conclusion as we did. At the Presidential AIDS Advisory Panel Meeting in Johannesburg, July 2000, we expressed the view that the only difference between the two sets of proteins was quantitative. Not qualitative. The then president of the South African Medical Research Council, William Makgoba, accused us of misinterpreting Bess' findings. In our subsequent correspondence with Julian Bess, he agreed that one could come to our conclusion. Therefore, since the same proteins are present in both the "purified HIV" and the "mock virus", a bright medical student could not fail to conclude that the proteins in the "purified HIV" are cellular proteins. If there are no viral proteins, there can be no virus.

We do not know why Julian Bess, for whom we have the highest regard, "has continued to work on vaccines targeting HIV" (2), if indeed he is doing so. You will have to ask him why.

In the same rapid response (8 May 2003), Tony Floyd wrote: "Does the other author cited (Gluschankof) provide any reason to doubt the existence of HIV or the validity of HIV testing?" Yes, Gluschankof did. In the introduction to his paper, Gluschankof wrote: "[HIV] used for biochemical and serological analyses or as immunogens is frequently prepared by centrifugation through sucrose gradients", but in none of the studies "the purity of the virus preparation has been verified". In other words, Gluschankof agreed with our longstanding claim that no proof existed up to 1997 that the "HIV" proteins and genome originated from a "purified" virus and tried to answer our equally longstanding request of electron micrographs showing "purified HIV". Again, if Tony had read Gluschankof's paper (3), he would have noticed that figure 2 consists of electron micrographs. In the two electron micrographs which are supposed to contain "purified HIV" the overwhelming majority of particles are vesicles (cellular fragments). The caption to these two electron micrographs reads "Purified vesicles…" not "Purified HIV". Also the very few particles present in the two electron micrographs "arrowed" as being "HIV" do not possess all the morphological features attributed to HIV. Furthermore, particles indistinguishable from "HIV" are present in the electron micrograph originating from non-infected cells.

Quoting from the abstract of a 2001 paper by Gluschankof (4), Tony Floyd wrote: "The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection." If Tony had read their paper, he would have seen that in this paper, the "Productive infection was assessed by, measuring p24gag in the culture medium using an HIV-1 p24 antigen enzyme-linked immunosorbent assay (ELISA) kit". There are two problems with this:

• The presence of HIV was determined an antibody-antigen reaction which has never been proven specific. That such a reaction cannot be used to prove HIV infection has been clearly demonstrated in the following study. In 1992, Jorg Shupbach, the principle author of one of the first four 1984 Science papers published by Gallo's group on HIV isolation, reported that the whole blood cultures of 49/60 (82%) of "presumably uninfected but serologically indeterminate individuals and 5/5 seronegative blood donors were found positive for p24".(5)

• There is no proof that p24 is an HIV protein. In 1983, Montagnier and his colleagues claimed to have proven that p24 was the main protein of HIV (6). As we wrote in a previous rapid response (13 March 2003) "According to Luc Montagnier, to characterise the HIV proteins the virus must be purified. Although in 1983 he and his group claimed to have done so, in 1997 he admitted that even after a "Roman effort", in the electron micrographs of their "purified" virus they could not see any particles with the "morphology typical of retroviruses."(7) Again, a bright medical student would conclude, as we did, that the p24 protein could not be an HIV protein or even the protein of any other retrovirus.

The BOTTOM LINE is that Tony Floyd or anyone else needs to present an ACCURATE ANALYSIS rather than merely quoting from abstracts and making conclusions merely from the abstracts and titles of papers. As we have repeatedly stated in previous rapid responses, if anyone wants to support the HIV theory of AIDS then it absolutely necessary to show that experiments have been performed yielding:

• Evidence proving that the HIV antibody tests are specific.

• Evidence proving that HIV is heterosexually transmitted.

• Evidence proving that HIV has been isolated/purified.

As we wrote in a previous rapid response (24 March 2003):

"To claim proof for specificity there MUST BE at least one study and a few confirmatory studies where the antibody antigen reaction (assuming that the antigens are HIV) is compared with the present or absence of HIV, that is, with HIV isolation/purification. This study must include a statistically significant number of both patients who have AIDS as well as patients who do not have AIDS but are sick. In addition, the test must be done blind.

Any study claiming proof for heterosexual transmission MUST satisfy at least the following conditions:

• Be prospective
• Use tests which have been proven to be specific
• Have a statistically meaningful population
• The results must be statistically significant and must exclude any other possible route of infection
• There should be at least a few confirmatory studies Until at least such proof exists resolving these two basic issues, scientists have no option but to question the HIV theory of AIDS."

To claim proof for purification/isolation there must be at least one study and a few confirmatory studies where the supernatant from infected cells is banded in sucrose gradients:

• Electron micrographs of the 1.16gm/ml band contain nothing else but particles within the morphological characteristics of retroviruses

• The particles are infectious. The experiment must use controls, that is, banded supernatant from non- infected cultures which, with the exception of "HIV", have been treated exactly in the same way as the infected cultures. Also this experiment must be performed blindly.

To continue a fruitful debate and for Tony Floyd or anyone else to support the HIV theory of AIDS, such experimental evidence must be presented.

References

(1) Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virology. 1997 Mar 31;230(1):134-44.

(2) Chertova E, Crise BJ, Morcock DR, Bess JW Jr, Henderson LE, Lifson JD. Sites, mechanism of action and lack of reversibility of primate lentivirus inactivation by preferential covalent modification of virion internal proteins. Curr Mol Med. 2003 May;3(3):265-72.

(3) Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ. Cell Membrane Vesicles Are a Major Contaminant of Gradient-Enriched Human Immunodeficiency Virus Type-1 Preparations. Virology 1997 230: 125-133

(4) Gondois-Rey F, Biancotto A, Pion M, Chenine AL, Gluschankof P, Horejsi V, Tamalet C, Vigne R, Hirsch I. Production of HIV-1 by resting memory T lymphocytes. AIDS. 2001 Oct 19;15(15):1931-40.

(5) Schupbach J, Jendis JB, Bron C, Boni J, Tomasik Z. False-positive HIV- 1 virus cultures using whole blood. AIDS 1992 6:1545-6

(6) Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux, C, Rozenbaum W, Montagnier L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983 220:868 -71

(7) Tahi D. Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998 5:30-34.

Competing interests:   None declared


Re: Where are the experiments which prove HIV isolation, sexual transmission and antibody specificit 23 May 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: Where are the experiments which prove HIV isolation, sexual transmission and antibody specificit

There are several dozen infectious molecular clones of HIV-1, HIV-2, SIVs from various non-human primate species, and even hybrids made between HIVs and SIVs (called SHIVs) which are in widespread use in labs all over the world.

Many of these infectious molecular clones can be purchased from the AIDS Reagent Repositories:


NIAID Reagents
UK Reagents
Albert Einstein Reagents
etc...

Others have not been submitted to these repositories, but can be obtained from the people who cloned them.

If the Perth Group would like to claim that density gradient ultracentrfugation is the ONLY acceptable method of isolating a virus, they should provide some evidence that any virus has ever been isolated by that method to their satisfaction, preferably another retrovirus. Density gradient centrifugation is just one of hundreds of methods of seperating biological (and other) materials. It seperates materials based on their boyant densities which is just one of many proterties. Before the biolgocical revolutions which ocurred in the late 20th century, such as Lambda phage library construction, monoclonal antibody production (including binding monoclonal antibodies to various matrices for the purposes of immunopurification), and DNA sequencing electron microscopy and crude serology (with polyclonal sera) were considered cutting-edge tools in virological identification. However, times have changed and many far more accurate technologies now exist.

Below are just a few of thousands of papers published on HIVs and SIVs that illustrate why infectious molecular clones (and techniques such as site-driected mutagenesis which can be used to identify individual amino acids that contribute to pathogenicity) are useful, indeed critical, to AIDS research.

Virology 2003 Mar 15;307(2):328-40
Analysis of the functional relationship between V3 loop and gp120 context with regard to human immunodeficiency virus coreceptor usage using naturally selected sequences and different viral backbones.
Bagnarelli P, Fiorelli L, Vecchi M, Monachetti A, Menzo S, Clementi M.
Istituto di Microbiologia, Universita di Ancona, Ancona, Italy.
ABSTRACT:
The human immunodeficiency virus type 1 (HIV-1) gp120 V3 loop plays a predominant role in chemokine receptor usage; however, other linear and nonlinear gp120 domains are involved in this step of the HIV-1 replication cycle. At present, the functional relationship between V3 and these domains with regard to coreceptor usage is unclear. To gain insights into the nature of this relationship in naturally selected viral variants, we developed a recombinant strategy based on two different gp120 backbones derived from CXCR4 (X4)- and CCR5 (R5)-tropic viral strains, respectively. Using this recombinant model system, we evaluated the phenotype patterns conferred to chimeric viruses by exogenous V3 loops from reference molecular clones and samples from infected subjects. In 13 of 17 recombinants (76%), a comparable phenotype was observed independently of the gp120 backbone, whereas in a minority of the recombinant viruses (4/17, 24%) viral infectivity depended on the gp120 context. No case of differential tropism using identical V3 sequence in the two gp120 contexts was observed. Site-directed mutagenesis experiments were performed to evaluate the phenotypic impact of specific V3 motifs. The data indicate that while the interaction of HIV-1 with chemokine receptors is driven by V3 loop and influenced by its evolutionary potential, the gp120 context plays a role in influencing the replication competence of the variants, suggesting that compensatory mutations occurring at sites other than V3 are necessary in some cases.
PMID: 12667802


Sevilya Z, Loya S, Duvshani A, Adir N, Hizi A.
Mutagenesis of cysteine 280 of the reverse transcriptase of human immunodeficiency virus type-1: the effects on the ribonuclease H activity.
J Mol Biol. 2003 Mar 14;327(1):19-30.
PMID: 12614605

Brunelle MN, Brakier-Gingras L, Lemay G. Replacement of murine leukemia virus readthrough mechanism by human immunodeficiency virus frameshift allows synthesis of viral proteins and virus replication. J Virol. 2003 Mar;77(5):3345-50. PMID: 12584361

Wei X, Liang C, Gotte M, Wainberg MA. The M184V mutation in HIV-1 reverse transcriptase reduces the restoration of wild-type replication by attenuated viruses. AIDS. 2002 Dec 6;16(18):2391-8. PMID: 12461412

J Virol 2002 Dec;76(23):12173-84
Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking. ,br>Williams M, Roeth JF, Kasper MR, Fleis RI, Przybycin CG, Collins KL.
Graduate Program in Cellular and Molecular Biology, University of Michigan. University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
ABSTRACT:
Nef, an essential pathogenic determinant for human immunodeficiency virus type 1, has multiple functions that include disruption of major histocompatibility complex class I molecules (MHC-I) and CD4 and CD28 cell surface expression. The effects of Nef on MHC-I have been shown to protect infected cells from cytotoxic T-lymphocyte recognition by downmodulation of a subset of MHC-I (HLA-A and -B). The remaining HLA-C and -E molecules prevent recognition by natural killer (NK) cells, which would otherwise lyse cells expressing small amounts of MHC-I. Specific amino acid residues in the MHC-I cytoplasmic tail confer sensitivity to Nef, but their function is unknown. Here we show that purified Nef binds directly to the HLA-A2 cytoplasmic tail in vitro and that Nef forms complexes with MHC-I that can be isolated from human cells. The interaction between Nef and MHC-I appears to be weak, indicating that it may be transient or stabilized by other factors. Supporting the fact that these molecules interact in vivo, we found that Nef colocalizes with HLA-A2 molecules in a perinuclear distribution inside cells. In addition, we demonstrated that Nef fails to bind the HLA-E tail and also fails to bind HLA-A2 tails with deletions of amino acids necessary for MHC-I downmodulation. These data provide an explanation for differential downmodulation of MHC-I allotypes by Nef. In addition, they provide the first direct evidence indicating that Nef functions as an adaptor molecule able to link MHC-I to cellular trafficking proteins. PMID: 12414957


Competing interests:   None declared


HIV - which is the simplest and most obvious truth 25 May 2003
Stephen T. Green,
Consultant Physician
Royal Hallamshire Hospital, Sheffield S10 2JF

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Re: HIV - which is the simplest and most obvious truth

I do despair of the human race when I read some of the comments to date in this debate. I can see the appeal of denying that HIV is a problem and is sexually transmitted - you can have as much unprotected sex as you like with whoever you like and all you will ned is the occasional shot of penicillin !!

So ! What if HIV does not cause a nasty disease and cannot be transmitted from person to person through the sexual route ? If this is not the case, I do wonder what killed the many patients I have worked with over the years who would have chosen life had they had a choice. Strangely enough, the introduction of drugs which act to diminish the reproduction of this retrovirus seem to stop HIV-positive people dying so quickly.

A thought struck me. If there is no problem, I wonder how many of those individuals who dispute that HIV is (a) a problem and (b) sexually transmitted would be happy to have regular unprotected sexual intercourse with an another human being who they know to be HIV-antibody positive and has a measurable viral load ? Let's have a show of hands.

Should they do so and subequently develop antibodies themselves to HIV and a measurable viral load, perhaps they might still continue to deny that this virus is associated with the development of a disease and avoid taking treatment, side effects or no side effects.

I have a suspicion that not too many sensible people would dispute that their chances of dying an unpleasant death with chronic diarrhoea and a mouth stuffed full of Candida albicans in about eight to ten years time would have been enhanced somewhat.

Or should I be changing the advice I give to my patients ? Perhaps I should advise the ill African patient in whom, this week, I found HIV antibodies that it is of no consequence, that they can have sex as often as they like with their HIV-negative partner, and they shouldn't bother taking any of the pot pourri of daft medications I have on offer. Lets introduce new, helpful, slogans like "Condoms suck - toss them out". I have to say that I suspect that I would be certified insane and struck off the medical register if I were to do such a thing - that is, if I had survived being trampled afoot in the rush by the (sensible) patient wishing to get the hands on the medications. Whether they work or not, I am quite satisfied with the weight gain patients with advanced HIV disease manifest and the very useful level of immune reconstitution which accompanies their taking these drugs, whether they work or not !. And I am quite happy to advise HIV-positive individuals to practice safer sex for their own sake, so as to avoid picking up another strain of HIV which might be resistant to more drugs than their current strain.

Perhaps we should all be looking outside molecular medicine for a bit of common sense - to quote Leo Tolstoy (1828-1920) "..I know that most men, including those at ease with problems of the greatest complexity, can seldom accept even the simplest and most obvious truth if it be such as would oblige them to admit the falsity of conclusions which they have delighted in explaining to colleagues, which they have proudly taught to others, and which they have woven, thread by thread, into the fabric of their lives".

So, all we need to do is decide which of those put forward here is the simplest and most obvious truth !. Debate on.

Competing interests:   None declared


Unravelling the truth 27 May 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: Unravelling the truth

Unravelling the truth

In his rapid response "HIV — which is the simplest and most obvious truth" (25 May 2003), Stephen Green states "I can see the appeal of denying that HIV is a problem and is sexually transmitted - you can have as much unprotected sex as you like with whoever you like and all you will need is the occasional shot of penicillin !!" We (the Perth Group) have never, never made such claims.

Regarding "what killed the many patients", if not "HIV", shouldn't we at least be considering poverty, malnutrition, and the many infectious pathologies associated with them; recreational drugs, either IV or oral; anally deposited semen?

We do "dispute that HIV is (a) a problem and (b) sexually transmitted". However, as we indicated in a previous rapid response "A critical examination of the evidence for the existence of HIV" (25th April 2003) we definitely do not advocate that people should "be happy to have regular unprotected sexual intercourse [anal] with an another human being" either HIV positive or negative.

We may consider treatment if Stephen Green or anybody else comes with evidence which proves:
• the existence of "HIV" specific antibodies;
• the existence of "HIV" specific viral load;
• "that this virus is associated [necessary for] with the development of a disease". (Association is not proof for causation).

We agree that people who have "chronic diarrhoea and a mouth stuffed full of Candida albicans" have an increasing chance of dying "in about eight to ten years time". However, it doesn't mean the cause of death is "HIV" or that they are "HIV"-infected (see our rapid response "A critical examination of the evidence for the existence of HIV" (25th April 2003- http://bmj.com/cgi/eletters/326/7387/495#31507). Having Candida albicans will result in a positive "HIV" antibody test in the absence of "HIV" (1)

Because the diagnosis of HIV infection dramatically changes peoples' lives, before you can advise your African patient that he/she is "HIV"- infected, you must have proof beyond reasonable doubt that you indeed found "HIV antibodies". Since:
• in Africa, it has been shown that the most extensive sexual education has no effect on the "HIV-1" incidence; (2)
• there is no proof that "HIV" can be acquired by vaginal intercourse; (3) on what grounds would you advise your patients not to "have sex as often as they like", as long as they don't practice anal intercourse?

If the drugs you prescribe do indeed lead to "weight gain" and a "very useful level of immune reconstitution", these may not be the result of their effect on "HIV" but on other infectious agents. Furthermore, it is possible that the same effect may be obtained by using less toxic drugs. (4)

As the first step in deciding "which is the simplest and most obvious truth", we suggest an in-depth and unbiased analysis of the many publications from the Multi-center AIDS Cohort study (MACS), the longest, largest and best-designed study in gay men.

References

(1) Papadopulos-Eleopulos E, Turner VF, Papadimitrious JM, et al. HIV antibodies: further questions and a plea for clarification. Current Medical Research and Opinion 1997 13: 627-634

(2) Kamaii A, Quigley M, Nakiyingi J, Kinsman J, et al. Lancet 2003 361: 645-652

(3) Papadopulos-Eleopulos E, Turner VF, Papadimitrious JM, Alfonso H, Page BAP, Causer D, Mhlongo S, Miller S, Fiala C. BMJ 2002 324:1034

(4) Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Alfonso H, Miller T. A critical analysis of the pharmacology of AZT and its use in AIDS. Current Medical Research and Opinion 1999 15:1s-45s.

Competing interests:   None declared


Condoms and Partner Choice are Important in Containing HIV 29 May 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308

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Re: Condoms and Partner Choice are Important in Containing HIV

I had previously cited de Vincenzi's longitudinal study published in the New England Journal of Medicine(1) which found that:

---
"Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV."
---

Various comments were made about this study such as:

> For de Vincenzi (1) to make the above claim, she had first to prove that heterosexual (vaginal) transmission of HIV takes place. She did not.

Another triumphant non-proof (deja vu?). The Padian Study was similarly misused above, with claims that it tried 'vigorously' to prove heterosexual transmission (whilst somehow failing to state that objective whatsoever in the paper!). This is analogous to, having sailed across the atlantic with no other stated intention, you are greeted after a successful journey with cries of 'AHAH! You set out to prove that the Earth was round and FAILED!!!'. Whatever.

de Vincenzi did not 'have to prove' anything other than present her findings that condom use were an effective way of reducing the transmission of HIV.

> In the de Vincenzi study there was a significant loss (19.5%) to followup.

Significant?

In a study of several hundred couples over a 20 month period, wouldn't you suggest that to retain just over 80% of those who commenced the study be a good thing?

Or are you suggesting that the loss of this 19.5% somehow distorted the result?

Or was this comment just a bit of 'padding'?

de Vincenzi did of course state that the

---
"proportion of couples lost to follow-up was not significantly associated with the center ... or with any of the sexual, demographic, or medical characteristics documented at the time of enrollment"
---

Another comment was:

> According to US researchers ... the data analysis is flawed.

I'm not sure that Ambati's Letter(2) qualifies as representing 'US researchers' in general, although he does challenge de Vincenzi's figures as suggested. If his questioning of the statistics is valid, then for the sake of consistency we should also note his conclusion:

---
"Choosing a partner who is not in any high-risk group provides a degree of protection that is at least three orders of magnitude higher than that afforded by condom use."
---

Or are you ignoring his conclusion and hoping to ride high on the 'flawed' comment?

de Vincenzi challenges his figures in her reply. Regardless of that, one author champions partner choice as more important than condoms, the other vice versa. Neither entirely DENY the importance of either condoms or partner choice in the transmission of HIV.

I doubt de Vincenzi or Ambati would be too upset at having their work misused to support alternative AIDS theories.

There's a lot of it going around.

References:

(1) de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med. 1994 Aug 11;331(6):341-6. PMID: 8028613 [Abstract]

(2) Ambati J, Ambati BK, Rao AM. Heterosexual transmission of HIV. N Engl J Med. 1994 Dec 22;331(25):1717-8; author reply 1718-9. PMID: 7969368

Competing interests:   None declared


Manipulations and misrepresentation of scientific facts only serve to fuel HIV/AIDS 30 May 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Manipulations and misrepresentation of scientific facts only serve to fuel HIV/AIDS

In a recent news article(1) The University of Natal vice-chancellor Professor Malegapuru Makgoba:

---
said there was little doubt that HIV caused Aids, as had been demonstrated by many carefully conducted experiments and clinical case studies. In contrast, there was no evidence that common African conditions such as poverty, malnutrition, and many chronic infectious diseases by themselves, singly or in combination, caused the characteristic immunodeficiency typical of Aids -- the progressive depletion of CD4+ cells.

"To conflate causation with cofactors through a mixture of pseudoscientific statements is scientifically and politically dangerous in societies where denial, chauvinism, fear and ignorance are rampant," Makgoba said.

He said that when taking history into account, it was not impossible to explain the mistrust that existed amongst South Africans towards perceived Western science and medicine.

"However, in such societies, the manipulations and misrepresentation of scientific facts only serve to fuel an epidemic such as HIV/Aids."

---

Some other good news(2) from South Africa - Dr Fareed Abdullah, the head of AIDS in the Western Cape:

---
"triple-therapy treatment for all pregnant women with HIV was now firmly on the cards for South Africa"
---

Glad the truth is getting through where it matters most.

References:

(1) Politics Has Subverted Aids Debate: Vice-Chancellor. South African Press Association (Johannesburg) May 23, 2003 http://allafrica.com/stories/200305240257.html

(2) Cape's HIV War Hots Up Cape Argus (Cape Town) Di Caelers. May 26, 2003 http://allafrica.com/stories/200305260021.html

Competing interests:   None declared


A modest proposal 29 May 2003
Aiden P. Gregg,
Reseach Fellow in Social Psychology
Department of Psychology, University of Southampton, SO17 1BJ

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Re: A modest proposal

The Perth Group contend that:

>To claim proof for purification/isolation there must be at >least one study and a few confirmatory studies where the >supernatant from infected cells is banded in sucrose >gradients:

>Electron micrographs of the 1.16gm/ml band contain nothing >else but particles within the morphological >characteristics of retroviruses

>The particles are infectious. The experiment must use >controls, that is, banded supernatant from non- infected >cultures which, with the exception of "HIV", have been >treated exactly in the same way as the infected cultures. >Also this experiment must be performed blindly.

Now, perhaps, as Dr. Foley contends, meeting these criteria is not the *only* way to prove beyond reasonable doubt that HIV, or anoy other virus, exists. However, do the Perth Group and Dr. Foley at least agree that meeting these criteria would be *sufficient* to prove the existence of HIV, and that failing to find any HIV after meeting these criteria would at least cast some doubt on the existence of HIV? If so, why doesn't some finicky bench scientist, with inclinations more empirical than argumentative, carry out the proposed series of experiments, and put an end to a protracted and acrimonious debate? The Perth Group would surely like to see their skepticism validated, while mainstream AIDS researchers would surely like to see these dissidents decisively refuted by an experiment that those dissidents have themselves proposed. How expensive can it be to conduct these studies? Is there no agency will fund them? Is there no philantropist who can be appealed to?

Even if most mainstream scientists are satisfied that HIV exists, would it not be sound scientific practice to conduct a rigorous experiment that demonstrates this anyway? Compare: The rationale for homeopathic medicine is surely nonsensical. [Most obviously, it is not possible to dilute individual atoms or molecules further, and it would in any case not be possible to clear distilled water of infinitesimal quantities of confounding substances.) I, and most mainstream scientists, don't believe that any experiment is necessary to explode homeopathy for the quackery it is. However, I, and several other mainstream scientists, nonetheless do believe that it is salutary to conduct methodologically rigorous studies that explode homeopathy empirically, for all to see.

So, would it not be equally salutary for mainstream AIDS researchers to explode the claims of dissidents by isolating, according to the Perth Group's specifications, the HIV they know exists? After all, HIV is not a phantom menace, a subatomic particle, or a postmodernist construction. Rather, it is a biological entity with well-defined properties that is the cause of a global pandemic. So why not just get it over with and run the studies the Perth Group recommend, thereby silencing them for good? Surely, mainstream HIV scientists could not be afraid of risking the refutation of a cherished hypothesis?

Aiden P. Gregg, Ph.D (Yale)

Competing interests:   None declared


Re: A modest proposal 1 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: A modest proposal

> However, do the Perth Group and Dr. Foley at least > agree that meeting these criteria would be *sufficient* > to prove the existence of HIV, and that failing to > find any HIV after meeting these criteria would at > least cast some doubt on the existence of HIV?

The criteria that the Perth group claim are needed are impossible to meet. No virus has ever met them and none ever will. Density gradient ultracentifugation can only "enrich" a virus preparation up to 80% to maybe 98% purity, it can never produce a 100% "pure" virus preparation free of all other materials. Several groups have made such preparations of HIV (as they have for FIV, SIV, EIAV and other lentiviruses) and shown that there is some cellular debris and microvessicles derived from the cell culture in these preparations. Even 100% virus particles will contain some cell-derived proteins, because lentiviruses are enveloped viruses and the lipid bilayer envelope carries with it some cellular proteins such as MHC molecules.

Infectious molecular clones on the other hand can be made 100% pure, free of even viral proteins, they are just naked DNA copies of the viral genome. There are thousands of other advantages of cloning, over crude density preps of viruses. Molecular genetics offers a whole world of research that was not available with pre-1970 techniques.

Competing interests:   None declared


Who studies healthy HIV positives ? 3 June 2003
Sang G. Hahn,
Professor
KAIST, Yusung, Taejon, Korea

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Re: Who studies healthy HIV positives ?

Who studies healthy HIV positives ? Who studies why they are still healthy after more than ten years ?

Who studies and compares T-cell countings of HIV positive groups and HIV negative groups ?

Who studies people who barely missed being labeled AIDS patients only because they are HIV negative ? Who studies why they are developing same symptoms as AIDS patients do without being HIV positive ?

Are there some published research papers which studied the above questions ?

Competing interests:   None declared


Re: Who studies healthy HIV positives ? 4 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: Who studies healthy HIV positives ?

There are dozens of research groups that study one or all of the above topics. In addition, there are also dozens of groups who study highly exposed yet uninfected people in order to determine correlates of protection from infection. Most of your questions relate to correlates of protection from disease progression after infection.

Anyone can search PebMed using NCBI Entrez or visit a local medical library and look up hundreds of research papers puclished by these groups. It turns out that there have been many different human and viral alleles identified that all contribute to long term non progression after infection and/or protection from infection in the first place. One of the first such human alleles discovered, for example, was the delta-32 allele of the CCR5 gene. After its linkage to highly exposed uninfected homosexual men was discovered, it was intensivley studied and discovered to be the gene for the major "coreceptor" for HIV-1 (the other coreceptor is the CXCR4 gene product). An example of a viral gene allele that has been linked to long term nonprogression is the delta-Nef allele of the Nef gene which was intensively studied in the Sydney (Australia) blood bank cohort. In that case, several people were all transfused with blood donated by a single donor, and most of these transfused people lived quite a long time with no symptoms (at least one of them has now died from AIDS). It turned out that there was a deletion in the Nef gene in the virus that these people were infected with.

HIV/AIDS denialists like to ignore all such studies, and pretend that almost no HIV research has been done since 1983 or so. They would like to convince people that AIDS researchers all over the world are not even sure if they have a virus to work with or not. In reality, HIV-1 and HIV-2 are two of the best-characterized viruses to date. They have been cloned, sequenced and analyzed in minute detail. X-ray crystal structures for several HIV proteins have been determined. The viral life cycle has been worked out in minute detail. Drugs which interfere with several aspects of the viral life cycle have been developed and those which interfere with reverse transcription and protease processing of the precursor proteins have been approved for human use. More recently a fusion inhibitor which interferes with viral fusion to the host cell membrane has also been approved for human use.

If you search MedLine or PubMed for "immunodeficiency long term nonprogression" you currently find 35 published papers. If you search for "immunodeficiency long term nonprogressor" you find 30 and "immunodeficiency LTNP" finds 58 published papers. Additionally, you can find hundreds of papers which discuss more moderate differences in disease progression rates. The definition of "long term nonprogressor" is designed to include only the most extreme cases where infection with HIV-1 appears to cause almost no harm after many years of infection. Many other research groups have explored factors that cause rapid to moderate or slow disease progression rates.

Competing interests:   None declared


Re: Re: A modest proposal 4 June 2003
Jamie Mills,
Medical SHO
Leicester Royal Infirmary, Infirmary Square Leicester LE1 5WW

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Re: Re: Re: A modest proposal

In response to Brian Foley's comments-

Did either Bess et al. or Gluschankof et al. approach 80% or even 98% purified virus, or what looks like purified virus?

Even with modern techniques of isolating pieces of DNA and viewing which proteins are produced, how is that proof of an exogenous and infective retrovirus?

If as both authors state that "contaminating microvesicles" contain both RNA and DNA, how can we be confident that what we currently know as the HIV genome is the HIV genome and not, in part at least, represented by the microsomal contents.

Also the current tests (ELISA) used by our local laboratories use proteins isolated from sucrose gradients,(as mentioned in accompanying leaflets), which by your own admission are not pure, and judging by the EM's produced are not approaching a reassusring margin of pure- whatever that may be. How do we then interpret positive "HIV" antibody tests when we do not know what the positive reaction is about? Microvesicle or "HIV" proteins.

If we then move on to western blots as a means of confirming a diagnosis, how many bands and which do you need to confirm a diagnosis? This varies considerably around the world and means a person may be HIV positive in Africa but hop on a plane and have the same test in Australia and be HIV negative! What does that mean for our patients?

Competing interests:   None declared


Faster Progression to AIDS and Death Occurs in Those With Higher Levels of HIV VIRUS 4 June 2003
Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia

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Re: Faster Progression to AIDS and Death Occurs in Those With Higher Levels of HIV VIRUS

There are many theories as to why some people last longer after becoming HIV-positive. Whilst most 'long-term survivors' eventually succumb to AIDS, there are plenty of studies available examining why some people might progress to AIDS slower than others. For example in a study published by the National Academy of Sciences(1):

---
"The more virus, the more rapidly lymphocytes are destroyed, the sooner the development of immunodeficiency, and consequently the faster the progression to AIDS and death."
---

The story of Jack Levine(2) provides a more personal account of a victim of HIV who ultimately had to face the reality of his disease and tragically succumbed to it.

References:

(1) Arnaout RA, Lloyd AL, O'Brien TR, Goedert JJ, Leonard JM, Nowak MA. A simple relationship between viral load and survival time in HIV-1 infection. Proc Natl Acad Sci U S A 1999 Sep 28;96(20):11549-53 http://www.pubmedcentral.gov/articlerender.fcgi?tool=pub med&pubmedid=10500214

(2) Jack Levine Memorial at http://www.virusscience.org/hiv/aids/jack_levine.htm

Competing interests:   None declared


Re: Re: Re: A modest proposal 5 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: Re: Re: A modest proposal

Jamie Mills asks:
"Did either Bess et al. or Gluschankof et al. approach 80% or even 98% purified virus, or what looks like purified virus?"

And the answer is YES. In the Bess paper, the HIV-1 isolate MN, clone 4 virus grown of CEM-SS cells produced a preparation that was more than 99% pure. They discuss why there are differences in purity depending on which cell line and which virus is used.

Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ.
Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations.
Virology. 1997 Mar 31;230(1):125-33.
PMID: 9126268

Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO.
Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations.
Virology. 1997 Mar 31;230(1):134-44.
PMID: 9126269

"...how is that proof of an exogenous and infective retrovirus?"

No single experiment is "proof" of anything, really. There are whole textbooks written about virology and retroviruses. I can't spell it all out here. Endogenous retorviruses do exist, they are found in the genomes of nearly all eukaryotes. If the virus in not found in the germ-line DNA of an organism, it is not defined as endogenous, it is exogenous. No complex retrovirus (such as the lentiviruses and the T-cell leukemia viruses) which carry regulatory genes (tat, rev, nef, vif, vpu, vpx etc) in addition to the gag pol and env retroviral genes, have ever been found in an endogenous state in any host. A few endogenous viruses have one or two potenital open reading frames in addition to gag, pol and env, but none are truly complex. The closest relative to lentiviruses found in the human genome are endogenous retroviruses such as HERV-K, and these retroviral elements are very clearly not HIV-1 or any other lentivirus.
As for infectious, the global pandemic of infections with many different subtypes and circulating recombinant forms derived from the HIV-1 M group of viruses pretty much answers that question. Whether one studies infectious molecular clones of HIV-1, or transmission chains such as the case of Nushawn Williams who infected 13 young women, or local or country-wide epidemics, the answer is always consistent.

"... our local laboratories use proteins isolated from sucrose gradients,(as mentioned in accompanying leaflets), ..."

How were those proteins grown before the sucrose gradient prpearation? Was it clone whole virus grown on human cells? Or was it just viral genes grown in E. coli? Do you observe a large false-positive rate with the tests you are using? Just because sucrose gradients of HIV-1 whole virus particles are contaminated with varrying levels of cellular vessicles when the virus is grown on human cell lines, does not mean that all sucrose gradients are useless for all purposes.

"...If we then move on to western blots as a means of confirming a diagnosis, how many bands and which do you need to confirm a diagnosis? This varies considerably around the world and means a person may be HIV positive in Africa but hop on a plane and have the same test in Australia and be HIV negative! What does that mean for our patients? ..."

No test of tests for any infection or any other medical condition (such as pregnancy for an example) is always 100% perfect. What this means for any patient, is that some human intelligence is required in interpretting results. There are dozens of possible logical reasons for either a false negative (very recent infection is the major one) or false positive (the patient has elevated levels of some antibody or antibodies that bind to HIV proteins) HIV ELISA test. This is why a single ELISA is not the recommended standard for diagnosis. A person truly cannot be HIV positive in one country and HIV negative in another. They can be "officially" diagnosed as such, but they are either infected or not regardless of that diagnosis. If a gets a positive pregnancy test result with one test and negative with another, it doesn't mean she is "partially pregnant", and the same principles hold true for diagnosing HIV infection or any other infection. More than 99% of people who are infected with HIV-1 develop antibodies to many different HIV-1 proteins over time, such that some bands on the western blot typically appear first, followed by others. Also, very late in AIDS progression antibodies to some ands on the western blot are prone to decline. The end result is that we should expect a temporal variance in the number of reactive bands within any one infected individual. It should also be noted that "reactivity" to a protein band on a western blot is not a binary condition (wither "yes" or "no") but an analog condition varying from weak to strong.

The end result is that both patients and doctors need to use other data besides the ELISA and WB tests and human intelligence to interpret that data. If a person has never had sex, never had a transfusion, never injected drugs and has a weakly positive ELISA and two weakly positive western blot bands, the sensible thing to do is to wait a few months and re-test to see if this was just a spurious problem. If the results are identical months later, then it might be worth finding out what is causing them (perhaps infection with HTLV, which is one of the closest relatives of the lentiviruses). On the other hand if reactivity has increased to a strong ELISA positive plus 3 or 4 strongly reactive western blot bands, there is little (but still some) doubt that the person is truly infected, and further tests should be done to find out for sure, and if so, to find out how this person could have become infected (perhaps they were not fully honest about sex, or IV drug use, or perhaps they will be the clue that uncovers a new route of transmission as Kimberly Bergalis was in the famous "Florida Dentist" case).

Competing interests:   None declared


A simple request from the Perth Group 5 June 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: A simple request from the Perth Group

A simple request from the Perth Group

In his rapid response "Re: Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity" (23rd May 2003), Brian Foley has not addressed our request given in the title of his rapid response. In order to avoid any misunderstanding before we address his claim "There are several dozen infectious molecular clones of HIV-1", it will prove helpful to define some terms including virus cloning.

DNA cloning- the production of identical copies of a DNA fragment, any DNA fragment, from an ancestral DNA fragment by splicing it into a suitable cloning vehicle, for example, a bacteriophage or plasmid;

Transfection- the introduction of exogenous DNA into cells and its ability to replicate and express itself in these cells. That is, transcription of DNA into RNA and translation of RNA into proteins. The genetic material does not have to be of viral origin and transfection can be achieved by various methods.

Virus cloning-the introduction into cells of genetic material, DNA or RNA, which has been proven beforehand to be the genome of a virus followed by the appearance in the same cells of viruses identical in every aspect to the viruses from which the genomic material originated.

Before one can claim proof of cloning of a retrovirus one must: (a) Obtain particles separated from everything else (isolated) and show that the particles contain, amongst other molecules, proteins and nucleic acids (RNA), and that the particle are indeed infectious; (b) Show a direct relationship between the particle nucleic acids and proteins, that is, the proteins are coded by the nucleic acids (the viral genome); (c) Introduce the viral genome (RNA or cDNA) into cells and show that the DNA (cDNA) is integrated into the cellular DNA and is transcribed into RNA and the RNA is translated into proteins (transfect the cells); (d) Show that the cells produce particles and the particle proteins are coded by the particle nucleic acids; (e) Show that the particle nucleic acids and proteins are identical with those of the ancestral particle and they too are viral particles.

In addition one must be aware that all cells contain retroviral genomes which, under appropriate circumstances may be expressed in culture, that is, both the cells in the culture from which the original particles were obtained as well as the transfected cells may release identical retroviral particles even if there is no cloning. Thus, when one attempts to clone a retrovirus, a control culture is of quintessential significance. The only difference between the control and the cells transfected with the viral genome should be that in the control cultures one should use some other nucleic acid for transfection. This is because, under suitable culture conditions, the very act of transfection may result in retroviral expression including the production of retroviral particles. It is obvious that retrovirus cloning is not synonymous with retrovirus isolation. In fact, for cloning one must isolate the virus twice. The first time to obtain the viral genome and the second to prove that if particles are released after introduction of the viral genome, they are identical with those from which the genome was originally obtained.

Not one of the five references Brian Foley provided contains any proof for HIV cloning. The most that can be claimed from these experiments is transfection with some nucleic acids which originated from material that either (a) predominantly contained cellular fragments and thus cellular RNA and DNA and a few particles which have some but not all of the morphology attributed to either the HIV or other retroviral particles or (b) consists of material which contain no particles having any of the morphology attributed to retroviruses. In other words, the transfection, if any, was of nucleic acids for which there is no proof they were either of HIV or any other retrovirus.

In his rapid response "Re: A modest proposal" (1st June 2003), Brian Foley states "Molecular genetics offers a whole world of research that was not available with pre-1970 techniques". We agree. But we also agree with the ex-editor of Nature, Sir John Maddox: "Is there a danger, in molecular biology, that the accumulation of data will get so far ahead of its assimilation into a conceptual framework that the data will eventually prove an encumbrance? Part of the trouble is that excitement of the chase leaves little time for reflection. And there are grants for producing data, but hardly any for standing back in contemplation".

We do not care what method is used to isolate HIV. As far as we are concerned the only important fact is to obtain material which overwhelmingly consists of particles with the morphology attributed to HIV and that such particles are infectious. We have concentrated on this method because: (a) all the HIV experts who have claimed to have isolated/purified HIV and thus to have proven its existence have used the method of banding in density gradients; (b) all the proteins used as antigens in the antibody tests and the "HIV" genome have been obtained from such banded material.

We repeat our simple request: "Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity?"

Competing interests:   None declared


Re: A simple request from the Perth Group 6 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: A simple request from the Perth Group

The Perth group claims that "...under suitable culture conditions, the very act of transfection may result in retroviral expression including the production of retroviral particles. ..."

Lentiviruses are easily differentiated from other retroviruses both at the morphological level (the lentiviruses emerge from the cell as spheres and develop an electron dense cone shaped core as they mature: see this review by Gelderblom for an overview) and at the molecular level (lentiviruses all contain a number of regulatory genes such as tat, rev, nef and vif, and regulatory elements such as the RRE where the Rev regulatory protein binds and the TAR element where the Tat regulatory protein binds) which allow anyone to determine if the viruses produced by a transfection are endogenous viruses (such as HERV-K) or truly lentiviruses.

More importantly than just using molecular clones to observe viral morphology (as Bess, Gelderblom and hundereds of others have done), the Perth group is surely aware that molecular clones have also been used to tease apart the individual regions of the HIV and SIV genomes that contribute to pathology. For example, Rhesus macaques have been infected with molecular clones (and/or virus particles produced in cell culture from those clones) that are identical in genomic sequence other than a few specific point mutations. The great difference in pathogenicity between two nearly identical viral clones, indicates that these few sites that differ between the two are indeed contributing greatly to the pathogenicity of the virus. See for example:

Marthas ML, Ramos RA, Lohman BL, Van Rompay KK, Unger RE, Miller CJ, Banapour B, Pedersen NC, Luciw PA.
Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac.
J Virol. 1993 Oct;67(10):6047-55.
PMID: 8371353

Dehghani H, Brown CR, Plishka R, Buckler-White A, Hirsch VM.
The ITAM in Nef influences acute pathogenesis of AIDS-inducing simian immunodeficiency viruses SIVsm and SIVagm without altering kinetics or extent of viremia.
J Virol. 2002 May;76(9):4379-89.
PMID: 11932405

Hirsch VM, Sharkey ME, Brown CR, Brichacek B, Goldstein S, Wakefield J, Byrum R, Elkins WR, Hahn BH, Lifson JD, Stevenson M.
Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification.
Nat Med. 1998 Dec;4(12):1401-8.
PMID: 9846578

"...In other words, the transfection, if any, was of nucleic acids for which there is no proof they were either of HIV or any other retrovirus. ..."

Electron microscopy can only show us the general morphology of a virus. EIAV, FIV, BIV and SIV all look identical via electron micrography. FIV, BIV, and EIAV are totally harmless to humans, only HIV-1 and HIV-2 are known to cause immune deficiency in humans. The complete genome sequences of these viruses or their molecular clones, on the other hand, tells us EXACTLY which virus is present. The researchers who create infectious molecular clones of HIVs, SIVs, SHIVs (SIV-HIV chimeric viral genomes) and other viruses sequence the genomes before and after mutagenesis and before and after infections of animals. This is indeed far better proof that these viruses are viruses, than any electron micrograph could ever provide.

Competing interests:   None declared


The request remains the same and is still pure and simple 12 June 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: The request remains the same and is still pure and simple

The request remains the same and is still pure and simple.

Brian Foley's rapid response "Re: Re: Re: A modest proposal" (5 June 2003) raises several questions. In this reponse we would like to address only one of them. In responding to Jamie Mills' question: "Did either Bess et al, or Gluschankof et al, approach 80% or even 98% purified virus, or what looks like purified virus?", Foley wrote: "And the answer is YES. In the Bess paper, the HIV-1 isolate MN, clone 4 virus grown of CEM-SS cells produced a preparation that was more than 99% pure." Our question is: "Where in the Bess paper is there proof that the "the HIV-1 isolate MN, clone 4 virus grown of CEM-SS cells produced a preparation that was more than 99% pure."?"

From our reading of the Bess paper we found that the only reference for a quantitative estimation of purity is as follows: "As an index of relative purity, the ratio of viral p24CA concentration to the sum of the HLA DR and â2-M concentrations was calculated for each preparation. The HIV-1(B)/H9 Clone 4 preparation was significantly MORE PURE IN THIS SENSE sense than the two prototypical HIV-1 producing cell lines, HIV-1(B)/H9 and HIV-1(MN)/H9. However, much better ratios were found for the HIV-1(MN) Clone 4/CEM-SS and HIV-1(MN) Clone 4/Daudi."(1) (emphasis ours).

For this ratio to be used even as an "index of relative purity", evidence must exist which proves at least the following: i. The p24 protein is an HIV protein. No such evidence exists. According to Montagnier: "analysis of the proteins of the virus demands mass production and purification. It is necessary to do that."(2) In 1983 Montagnier claimed to have purified HIV and thus to have shown the existence of the p24 HIV protein. This claim has been widely accepted by many people including Brian Foley. However, in an interview he gave to the French journalist Djamel Tahi, after repeated questioning, Montagnier gave the astonishing reply, namely, that in what they called "purified virus" they did not have even particles with "the morphology typical of retroviruses". (2) This means that there is no proof that p24 is even a retroviral protein. ii. That the ratio between the different cellular proteins is constant. No such evidence was presented. In fact, according to Bess et al: "Previous reports have indicated that infection of T-cell lines can up- regulate, down-regulate, or have no effect on the cell surface expression of various cellular proteins".(1) In addition, the CEM-SS cells contains low amounts of â2-M proteins and "Implicitly, microvesicles purified from cell lines such as CEM-SS and MOLT-3 that do not produce HLA-DR did not contain any HLA-DR". (1) This fact alone will result in a high ratio even if the purity is extremely low.

This means that the purity of the viral preparation cannot be determined from the "ratio of viral p24CA concentration to the sum of the HLA DR and â2-M concentrations" as Brian Foley seems to have done.

The only way to estimate purity is to perform a careful examination of the electron micrographs. Perhaps we need to remind Dr. Foley how to judge such purity. One studies a given, single object in the EM and then compares it with all those immediately surrounding it. Then this procedure is repeated for every other object in the EM. If the overwhelming objects are identical then we can deduce the material is virtually pure. Applying this procedure to Bess' EM it is child's play to recognise that whatever Fig 3 in the Bess paper represents, it is not pure. That is, neither the purified HIV-1(MN) or the purified HIV-1(MN) Clone 4 electron micrographs show an HIV-1 purity of either 99% or in fact even 80%. Furthermore, none of the particles arrowed as being HIV have the morphological characteristics attributed to HIV or even to retroviruses. There is no correlation even in their diameters. Retroviruses have a diameter of 100-120 nm while the diameters of the particles in the two electron micrographs assumed to be HIV have an average diameter of 234 nM with none of these particles having a diameter of less than 160 nM. By just this criterion alone it is impossible to claim this material contains even a retrovirus, pure or impure.

In his rapid response "Re: A simple request from the Perth Group" (6 June 2003), Brian Foley wrote: "The Perth group claims that "…under suitable culture conditions, the very act of transfection may result in retroviral expression including the production of retroviral particles. …" This is not a claim. This is a fact.

Brian Foley also wrote: "Lentiviruses are easily differentiated from other retroviruses both at the morphological level…and at the molecular level…". If HIV is a lentivirus and lentiviruses can be so easily differentiated from other retroviruses then why, on the basis of morphology, did Montagnier describe HIV firstly as a typical type-C particle then a type-D particle and ultimately as a lentivirus? Similarly, why did Gallo for many years insist HIV belongs to the same family as HTLV-I (an oncovirus)? (3) To differentiate HIV from other retroviruses at the molecular level, firstly HIV must be purified and its genomes sequenced. Since HIV has not been purified it follows the HIV genome could not have been characterised.

Brian Foley further wrote: "…using molecular clones to observe viral morphology…the Perth group is surely aware that molecular clones have also been used to tease apart the individual regions of the HIV and SIV genomes that contribute to pathology." Retroviruses are not simply molecules but particles whose constituents include lipids, proteins and RNA. Their morphology cannot be determined by using molecular clones which are only a string of nucleic acids. How can we be aware of "individual regions of the HIV" genome "that contribute to pathology" when as we have pointed out in a previous rapid response "A simple request from the Perth group" (5 June 2003) that the "HIV genome" "originated from material that either predominantly contained cellular fragments and thus cellular RNA and DNA and a few particles which have some but not all of the morphology attributed to either HIV or other retroviral particles; or consist of material which contain no particles having any of the morphology attributed to retroviruses."?

Again, we repeat our request, pure and simple: "Where are the experiments which prove HIV isolation and thus the existence of the HIV genome, sexual transmission and antibody specificity?"

References

(1) Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virology. 1997 Mar 31;230:134-44.

(2) Tahi D. Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998 5:30-34.

(3) Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. (1993). Is a positive Western blot proof of HIV infection? Bio/Technology 11:696-707.

Competing interests:   None declared


Re: The request remains the same and is still pure and simple 12 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: The request remains the same and is still pure and simple

Again I repeat "If the Perth Group would like to claim that density gradient ultracentrfugation is the ONLY acceptable method of isolating a virus, they should provide some evidence that any virus has ever been isolated by that method to their satisfaction, preferably another retrovirus. "

The Perth group is using a simple "straw man" argument, in claiming that their method is the only acceptable method of analyzing a virus, when in fact their method has requirements included which make it IMPOSSIBLE to follow. It is well known that lentiviruses have mature and immature forms, with the electron dense core gradually forming as the viral particles mature. Thus any photograph of HIV or SIV or EIAV shows viral particles that are not all 100% identical.

Density gradient ultracentifugation is also rather harmful to viruses so that the viral particles loose much or all of their ability to infect cells after this treatment. In addition to osmotic stress from the solutes used to generate the density gradient, there is also physical stress of ultracentrifugation which tends to remove viral envelope glycoprotein spikes.

If the Perth group believes that their method is valid for studying viruses, they should be able to name at least one virus which has been studied using their criteria. Where is the evidence that ANY virus has EVER been "purified" to their satisfaction??????

Competing interests:   None declared


Where is the proof for HIV purification by any method? 19 June 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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Re: Where is the proof for HIV purification by any method?

Where is the proof for HIV purification by any method?

In the rapid response "Re: The request remains the same and is still pure and simple" (12 June 2003), Brian Foley wrote: "Again I repeat "If the Perth Group would like to claim that density gradient ultracentrifugation is the ONLY acceptable method of isolating a virus, they should provide some evidence that any virus has ever been isolated by that method to their satisfaction, preferably another retrovirus". Brian Foley does not appear to have read our rapid response "A simple request from the Perth Group" (5 June 2003) in which we wrote: "We do not care what method is used to isolate HIV. As far as we are concerned the only fact of importance is to obtain material which consists predominantly of particles with the morphology attributed to HIV and that the particles are infectious."

Brian Foley also wrote "The Perth group is using a simple "straw man" argument, in claiming that their method is the only acceptable method of analysing a virus…". The method of banding in density gradients is not our method. This is the method of: i. Barre-Sinoussi and Chermann, the principal and the 2nd author of the 1983 Montagnier et al paper who, in 1973, used it to purify the murine sarcoma virus and to obtain material which contained nothing else but particles with "No apparent differences in physical appearance" (1) ii. many other virologists who used it "to prepare highly purified concentrates of these relatively high yield viruses [murine, feline and avian retroviruses]. The same techniques have been used for the recovery of other viruses, particularly the low-yield viruses found in cell cultures of human origin such as the ESP-1 type C virus and the Epstein- Barr herpesvirus." (2) iii. Bader, the renowned retrovirologist, according to whom "centrifugation to equilibrium in density gradients is the preferred technique for purification of RTV" (3) iv. Montagnier (4) and Gallo (5),(6) who used it to isolate / purify HIV and thus prove its existence.

Brian Foley wrote that the method of banding in density gradients: "has requirements included which make it IMPOSSIBLE to follow". If this is the case then why has he accepted Montagnier's and Gallo's claim to have purified HIV by this method and thus to have proven the existence of the HIV genome and proteins, that is, the existence of a unique human retrovirus?

Brian Foley wrote: "It is well known that lentiviruses have mature and immature forms, with the electron dense core gradually forming as the viral particles mature. Thus any photograph of HIV or SIV or EIAV shows viral particles that are not all 100% identical". It is true that in the culture supernatant there are mature and immature particles and thus the particles "are not all 100% identical". However all the banded particles are mature which means that they should be identical.

Brian Foley wrote: "Density gradient ultracentrifugation is also rather harmful to viruses so that the viral particles loose much or all of their ability to infect cells after this treatment". If this is the case then: i. why is banded material used to infect cultures? ii. why does Factor VIII contain infectious HIV particles when its manufacturing is even more taxing on retroviral particles than banding in density gradients?

Brian Foley wrote: "In addition to osmotic stress from the solutes used to generate the density gradient, there is also physical stress of ultracentrifugation which tends to remove viral envelope glycoprotein spikes". This implies that the particles have spikes prior to banding. Although spikes are one of the main features of retroviral particles, so far nobody, not even Hans Gelderblom has published proof that such spikes are present on the cell-free "HIV" particles.

Brian Foley wrote: "If the Perth group believes that their method is valid for studying viruses, they should be able to name at least one virus which has been studied using their criteria. Where is the evidence that ANY virus has EVER been "purified" to their satisfaction??????" An example of purification is found in references (1) and (7).

References

(1) Sinoussi F, Mendiola L, Chermann JC, Jasmin C, Raynaud M. (1973) Purification and Partial Differentiation of the Particles of Murine Sarcoma Virus (M. MSV) According to their Sedimentation Rates in Sucrose Density Gradients. Spectra 4:237-243.

(2) Toplin I, Sottong P. (1972) Large-Volume Purification of Tumor Viruses by Use of Zonal Centrifuges. Applied Microbiology 23: 1010-1014.

(3) Bader, J.P. 1975. Reproduction of RNA Tumor Viruses, p.253-331. In:Comprehensive Virology Vol.4. H. Fraenkel-Conrat, R.R. Wagner (Eds.). Plenum Press, New York.

(4) Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioun C, Rozenbaum W, Montagnier L (1983) Isolation of a T-Lymphotrophic Retrovirus from a patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science 220:868-871.

(5) Schupbach J, Popovic M, Gilden RV, Gonda, M. A., Sarngadharan, M. G., Gallo, R. C. (1984) Serological analysis of a Subgroup of Human T- Lymphotrophic Retroviruses (HTLV-III) Associated with AIDS. Science 224:503-505.

(6) Sarngadharan M, G., Popovic M, Bruch L. (1984). Antibodies Reactive to Human T-Lymphotrophic Retroviruses (HTLV-III) in the Serum of Patients with AIDS. Science 224:506-508.

(7) Crawford LV, Crawford EM. (1961) The Properties of Rous Sarcoma Virus Purified by Density Gradient Centrifugation. Virology 13:227-232.

Competing interests:   None declared


Distinguishing between true and "official" HIV infection 20 June 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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HIV infection

Distinguishing between true and "official" HIV infection

Brian Foley concedes no tests are 100% perfect. Presumably his caveat applies to the HIV antibody tests. This means that before antibody test parameters are verified a scientist must acknowledge the possibility that an unknown proportion of antibody positive patients are not HIV infected. This leads to two questions: what is the proportion and how do we find out? Both are highly significant because it is most undesirable to introduce the test into routine clinical practice before this parameter is ascertained. We will ignore false negatives because physicians and patients most often want to know whether or not an already positive test means HIV infection. Brian Foley correctly identifies at least one reason why a positive test does not necessarily indicate HIV infection. Namely "the patient has elevated levels of some antibody or antibodies that bind to HIV proteins". He then arrives at an explanation of how appearing and disappearing Western blot bands argue the need for "both patients and doctors need to use other data besides the ELISA and WB tests and human intelligence to interpret that data". This is followed by an example to illustrate how "both patients and doctors" might apply themselves to this task. (Do patients really play a role in interpreting their own tests?) The crux of Foley's interpretation revolves around the time of appearance and the numbers of "weak" or "strong" WB bands. Apparently "two weakly positive western blot bands" may or may not be HIV but "a strong ELISA positive plus 3 or 4 strongly reactive western blot bands" definitely are HIV. Is this system ex cathedra or does Brian have proof? If he has proof what is it? Notwithstanding, is he aware that in the MutiCenter AIDS Cohort Studies, up till 1990 one "strong" WB band was proof of HIV infection? 1 Were "the one strong band" members of this cohort of 5000 gay men "truly HIV-infected" or not? We should also note that Brian's criteria are yet another set we could add to the list of global criteria for a positive Western blot (see the chart at the end of this posting and in reference 13).

Not surprisingly, patients are about as interested in the arcane and ludicrous distinctions between being "officially" or "unofficially" infected as they are in being "partially pregnant". They just want to know if they're infected. Is the patient one of the lucky ones whose "elevated levels of some antibody or antibodies that bind to HIV proteins" are not HIV antibodies? Given that AIDS patients are characterised by hypergammaglobulinaemia, that is, they have "elevated levels of some antibody or antibodies", because of antibody cross-reactivities it is more than likely that many and perhaps 100% of the antibodies which "bind to HIV proteins" are not HIV antibodies at all. 2-4 Note this would not negate a correlation between a positive test and AIDS. That is a completely different matter and we trust Brian is cognisant of the distinction. Correlations between diseases and non-specific tests are well recognised and are of great clinical utility. Both in diagnosis, prognosis and predicting the success or failure of treatments. For example, the humble temperature measurement. Or, more attuned with antibody tests, measurements of the erythrocyte sedimentation rate (ESR). 5

As mentioned, Brian's criteria involve arbitrary appearances and numbers of "weak" and "strong" ELISAs and WB bands. It goes without saying this is not proof of antibody test specificity. If Brian were handed a small object resembling an apple, does giving him a ton of the same but larger three weeks later prove it truly is an apple? The problem with Brian's, as with all other criteria, is that as real physicians, talking to real patients outside laboratories, we might get stuck with a patient who wants to know the trick of how HIV experts including the CDC and the WHO 6 distinguish between "real" HIV antibodies and the "pretenders". Obviously one cannot tell merely by inspecting the test tube or paper strip. All we see there is a colour change. Evidence that a reaction has taken place. To cut to the chase and as we have argued elsewhere, 2-4 7-13 the only way to document what proportions of reactions are and are not HIV is to compare the presence or absence of reactions with the presence or absence of HIV itself. That is, against an HIV isolation gold standard. This has never been reported but nonetheless was and always will remain a fundamental requirement.

At the risk of being repetitive, 13 in regard to HIV isolation it is well worth considering what this would mean if an attempt were made to apply Montagnier's and Gallo's method to verification. Their method of HIV isolation means this: When cells from AIDS patients are cultured with mitogens and other chemical agents, after a few weeks the cultures (a) reverse transcribe artificial primer-template RNAs; (b) contain a few particles bearing some resemblance to retroviral particles; (c) contain some proteins which react with antibodies present in the serum of AIDS patients. These are the data Montagnier and Gallo presented in Science in 1983/84 as proof of the existence of HIV. Yet (a) reverse transcription is a property of all cells, healthy or unhealthy; 14 15 Normal, mitogenically stimulated "non-HIV-infected" lymphocytes reverse transcribe; 16 17 (b) retroviral-like particles are ubiquitous. 18 As Gallo himself pointed out in 1976, "virus‑like particles morphologically and biochemically [which reverse transcribe] resembling type‑C virus but apparently lacking the ability to replicate, have been frequently observed" in human leukaemias. 19 Particles identical to HIV are found in the majority of normal, human placentas. 20 Particles indistinguishable from HIV are found as frequently (90%) in the enlarged lymph nodes of patients without AIDS or immune deficiency as those with AIDS; 21 (c) as Dr. Foley reminds us, antibodies react with many different substances, not just those which induce their formation. 22 A reaction does not confer "ownership" of either antibody or protein to a unique retrovirus, or indeed to any other object. If this were scientifically valid one could claim that acid curdling milk proves the milk is from a cow and the acid from a lemon. It is precisely because antibodies are not monogamous that their reactions must be verified against an independent gold standard.

In 1997 Montagnier, the discoverer of HIV, admitted he could not find particles "with the morphology typical of retroviruses" in EMs of his "purified virus". He also stated that to obtain its proteins HIV must be purified but he had not purified HIV. In his opinion neither had Gallo. 11 13 23-25 Neither has anybody else since. Which means that the "HIV" proteins originate from material which has never been proven to contain retroviral particles. Since reverse transcription is a property of all cells and retroviral-like particles are ubiquitous, any attempt to use the Montagnier and Gallo method of isolation to validate the antibody tests would amount to using an antibody test as its own gold standard.

Dr. Foley can inspect the passing parade of ELISAs and Western blot strips from now till eternity but he will not be able to discern which particular antibodies are causing the colour change. All could be due to a retrovirus HIV for whose existence scientific proof may one day be forthcoming. Or none could be due to HIV. Eighteen years after the tests were introduced it is clear, at least in the risk groups, that a positive antibody test is related to AIDS. However, what is very clear is we still don't know if the positive test is caused by a retroviral infection. It remains inexplicable why scientists have ignored the need to prove the specificity of the HIV antibody tests for HIV infection. If the antibody tests do not prove infection with a retrovirus then a vast amount of the effort expended in combating AIDS is based on an arrant misapprehension. This can only be viewed as a gross waste of resources.

REFERENCES

1. Phair J, Jacobson L, Detals R, Rinaldo C, Saah A, Schrager L, et al. Acquired Immune Deficiency Syndrome Occuring Within 5 Years of Infection with Human Immunodeficiency Virus Type-1: The Multicenter AIDS Cohort Study. Journal of Acquired Immune Deficiency Syndromes 1992;5:490-496

2. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Is a positive Western blot proof of HIV infection? Bio/Technology 1993;11:696-707

3. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. HIV antibodies: Further questions and a plea for clarification. Current Medical Research and Opinion 1997;13:627-634

4. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Page B. HIV antibody tests and viral load - more unanswered questions and a further plea for clarification. Current Medical Research and Opinion 1998;14:185-186

5. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, et al. High rates of HIV seropositivity in Africa-alternative explanation. International Journal of STD and AIDS 2003

6. National Institute of Allergy and Infectious Diseases. Focus on the HIV-AIDS Connection, 2001. www.niaid.nih.gov/news room/focuson/hiv00/default.htm

7. Papadopulos E, Turner V. Presentation to the Presidential Panel AIDS Advisory Meeting 3 & 4 July Johannesberg, South Africa. 2000. www.theperthgroup.com/aids/pretoria2.doc

8. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Hedland-Thomas B, Causer D, Page B. Chart of the global variation in the criteria for a positive HIV Western blot, 1993.www.theperthgroup.com/aids/WBCHART.pdf

9. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Has Gallo proven the role of HIV in AIDS? Emergency Medicine [Australia] 1993;5:113-123

10. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. The Isolation of HIV: Has it really been achieved? Continuum 1996;4:1s-24s.www.virusmyth.com/aids/data/epreplypd.htm

11. Papadopulos-Eleopulos E. A critical analysis of the evidence for the existence of HIV and the HIV antibody tests: Presentation via satellite to the XIIth International AIDS Conference, Geneva. 1998 (June 28th). www.virusmyth.com.aids/perthgroup/geneva

12. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, et al. Mother to Child Transmission of HIV and its Prevention with ATZ and Nevirapine. Perth: The Perth Group, 2001.

13. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BA, Causer D. A critical analysis of the evidence for the existence of HIV. Electronic British Medical Journal 2003. http://bmj.com/cgi/eletters/326/7387/495#31507

14. Varmus H. Reverse Transcription. Scientific American 1987;257:48-54

15. Varmus HE. Reverse transcription in bacteria. Cell 1989;56:721-724

16. Gallo RC, Sarin PS, Wu AM. On the nature of the Nucleic Acids and RNA Dependent DNA Polymerase from RNA Tumor Viruses and Human Cells. In: Silvestri LG, editor. Possible Episomes in Eukaryotes. Amsterdam: North-Holland Publishing Company, 1973:13-34.

17. Tomley FM, Armstrong SJ, Mahy BWJ, Owen LN. Reverse transcriptase activity and particles of retroviral density in cultured canine lymphosarcoma supernatants. British Journal of Cancer 1983;47:277-284

18. Frank H. Retroviridae. In: Nermut MV, Steven AC, editors. Animal Virus and Structure. Oxford: Elsevier, 1987:253-256.

19. Gallo RC, Wong-Staal F, Reitz M, Gallagher RE, Miller N, Gillespie DH. Some evidence for infectious type-C virus in humans. In: Balimore D, Huang AS, Fox CF, editors. Animal Virology. New York: Academic Press Inc., 1976:385-405.

20. Panem S. C Type Virus Expression in the Placenta. Current Topics in Pathology 1979;66:175-189

21. O'Hara CJ, Groopman JE, Federman M. The ultrastructural and immunohistochemical demonstration of viral particles in lymph nodes from human immunodeficiency virus-related and non-human immunodeficiency virus-related lymphadenopathy syndromes. Human Pathology 1988;19:545-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3371979

22. Nossal GJV. Antibodies and Immunity. Harmondsworth, UK: Penguin Books Ltd, 1971.

23. Tahi D. Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998;5:30-34. www.virusmyth.com/aids/data/dtinterviewlm.htm

24. Weiss R, Turner, VF. Email debate on the existence of HIV, 1999. www.virusmyth.com/aids/perthgroup/papers2.html

25. Turner VF, Weiss R. Email debate with Professor Robin Weiss on the existence of HIV. 1999. www.theperthgroup.com/aids/vftweiss.html

GLOBAL VARIATION OF THE CRITERIA DEFINING A POSITIVE HIV WESTERN BLOT

33450.gif

AFR=AFRICA;1 AUS=AUSTRALIA;2 FDA=US FOOD AND DRUG ADMINISTRATION;3 RCX=US RED CROSS;3 CDC=US CENTER FOR DISEASE CONTROL;3 CON=US CONSORTIUM FOR RETROVIRUS SEROLOGY STANDARDIZATION;3 GER=GERMANY; UK=UNITED KINGDOM; FRA=FRANCE; MACS= US MULTICENTER AIDS COHORT STUDY 1983-1992. * Bands not in electrophoretic order

NOTES:

I. "The Association of Public Health Laboratories now recommends that patients who have minimal positive results on the WB, eg p24 and gp160 only, or gp41 and gp160 only, be told that these patterns have been seen in persons who are not infected with HIV and that follow-up testing is required to determine actual infective status".4

II. In February 1993 the US Food and Drug Administration relaxed their criteria in order to "reduce the number of HIV-1 seroindeterminate Western blot interpretations", that is, to increase the number of HIV positive individuals.5

1. WHO. (1990). Acquired Immunodeficiency Syndrome (AIDS). Proposed criteria for interpreting results from Western blot assays for HIV-1, HIV-2 and HTLV-I/HTLV-II. Weekly Epidemiological Record 65:281-298.

2. Healy DS, Maskill WJ, Howard TS, et al. (1992). HIV-1 Western blot: development and assessment of testing to resolve indeterminate reactivity. AIDS 6:629-633.

3. Lundberg GD. (1988). Serological Diagnosis of Human Immunodeficiency Virus Infection by Western blot Testing. Journal of the American Medical Association 260:674-679. (Data presented in this paper reveal that when the FDA criteria are used to interpret the HIV Western blot less than 50% of US AIDS patients are HIV positive whereas 10% of persons not at risk of AIDS are also positive).

4. Mylonakis E, Paliou M, Greenbough TC, Flaningan TP, Letvin NL, Rich JD. Report of a false-positive HIV test result and the potential use of additional tests in establishing HIV serostatus. Archives of Internal Medicine 2000;160:2386-8.

5. Keinman S, Busch MP, Hall L, et al. (1998). False-positive HIV-1 test results in a low -risk screening setting of voluntary blood donation. Journal of the American Medical Association 280:1080-1083.

Each horizontal band on the left represents a protein with which an antibody can react. Serum from a patient is added to a strip and the strip developed. Where there have been antibodies reacting a coloured band develops. The number and location determining a positive test, for the same virus, varies all over the world.

This gives rise to the incongruity where, for example, an individual positive in New York City on the CDC criteria would not be positive in Sydney, Australia. Or an Australian positive with p41, p32, p24 and p18 bands would not be positive in Africa. Or an African positive with a p41 and p120 band would not be positive in Australia, parts of the US or Europe. Confusion over antibody reactivity is confirmed in diagnostic laboratory manuals. The Genelabs Diagnostic HIV BLOT 2.2 Western blot Assay Instruction Manual advises, "Specific guidelines for interpretation may differ depending on the local policies, GENELABS recommends following the accepted policy to be in accordance with local regulations". This is followed by seven different criteria for defining a positive Western blot issued by "different international regulatory bodies". Genelabs also append, "We recommend the following guidelines for the interpretation of the Genelabs Diagnostic HIV BLOT 2.2" and list an eighth set of criteria for a positive Western blot (Packet Insert, 1998). This means that "different international regulatory bodies" or "local policies", and not the presumed pathogen determine patterns of antibody reactivity said to prove a retroviral infection. Manufacturer Bio-Rad advises "Each laboratory performing Western blot testing should develop its own criteria for band interpretation. Alternatively, band interpretation may be left to the clinician" (Bio-Rad Laboratory Manual 1993).

Competing interests: None declared


If It's Good Enough for RSV, Then It is Good Enough for HIV. 24 June 2003
Tony Floyd,
Medical Student
Newcastle University

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Re: If It's Good Enough for RSV, Then It is Good Enough for HIV.

It has been posited above that:

>an individual positive in New York City on the CDC criteria would not be positive in Sydney, Australia.

How extraordinary. Is there even one patient that you are aware of that this theory would apply to?

Is there anyone who, confirmed positive by all tests in New York, would then not be positive by the usual series of tests in Sydney?

Or is it just a one-in-a-million hypothetical?

In which case it deserves as much attention as the plethora of other alternative AIDS arguments.

***************************************************

The attempted side-step of Brian Foley's question deserves attention:

What he asked was:

> If the Perth group believes that their method is valid for studying viruses, they should be able to name at least one virus which has been studied using their criteria. Where is the evidence that ANY virus has EVER been "purified" to their satisfaction?

This was in no way satisfied by merely providing references to a paper from 1961 about the Rous Sarcoma Virus and from 1973 about the Murine Sarcoma Virus.

No indication was given as to why the papers might support the use of Density Gradient Centrifugation as a valid means of proving the existence any virus these days?

Why have even the two little known viruses mentioned not been associated with this separation technique in the last 30 years?

If you did cite the 1961 paper on Rous Sarcoma Virus as an example of a virus purified to your satisfaction, is it not ironic that RSV is a retrovirus very similar to HIV? In fact the fusion protein and an envelope glycoprotein precursor have been shown to be similar in both viruses(1)

If you are satisfied about the purification of RSV, then why is HIV so different?

Do you except that there might be a chance that all the infectious disease experts, virologists and vaccine developers around the world are working with a very real virus called HIV?

References:

(1) Streckert HJ, Werchau H. Epitopes at the proteolytic cleavage sites of HIV-1-gp120 and RSV-F protein share a sequence homology: comparative studies with virus-induced and antipeptide antibodies. Intervirology. 1992;34(1):30-7. PMID: 1385356

Competing interests:   None declared


Re: Condoms and Partner Choice are Important in Containing HIV 25 June 2003
Matthew L Grove,
Consultant Rheumatologist
NTGH, NE29 8NH

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Re: Re: Condoms and Partner Choice are Important in Containing HIV

In Tony Floyd's response of the 29th May, he quotes Vincenzi's longitudinal study (1)as proof that the HIV positive state is transmitted by a virus:

"Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV"

Dr. Papadopulos-Eleopulos counters "For de Vincenzi (1) to make the above claim, she had first to prove that heterosexual (vaginal) transmission of HIV takes place. She did not."

Surely it is not necessary to prove any such thing? The data clearly proves my hypothesis that regular topical application of latex to the vaginal wall reduces the incidence of spuriously positive HIV antibody tests... no transmission of any kind need be involved.

Competing interests:   Resolutely living on my flat earth.


Re: HIV in South Africa 25 June 2003
Matthew L Grove,
Consultant Rheumatologist
NTGH, NE29 8NH

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Re: Re: HIV in South Africa

In her initial detailed submission to this debate of the 13/3/2003, Dr. Papadopulos-Eleopulos sets out in detail the evidence that "The only sexual act, in both gay and heterosexual sex, which is related to the appearance of AIDS and a positive antibody test is receptive anal intercourse"

She then concludes:

"Since the main and absolutely necessary property of sexually transmitted agents is bidirectionality, that is, transmission from the passive to the active partner and vice versa, this means HIV cannot be sexually transmitted."

What? How is that?

My knowledge of such matters is purely theoretical - but surely both partners in a male homosexual relationship can be either passive or active in any given sexual act, and may be active on one occasion and passive on another. So transmission is bidirectional.

This argument could pertain for the heterosexual case, but the data to the contrary has been well-rehearsed above.

Competing interests:   None declared


Re: Where is the proof for HIV purification by any method? 26 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: Where is the proof for HIV purification by any method?

The Perth group says "The method of banding in density gradients is not our method." and I realize that, but it is the Perth group who placed further requirements on this method in order to claim that HIV-1 has never been purified by this method. Of course thousands of HIV researchers have used sucrose and other density gradient preparations of HIV-1, HIV-2 and various SIVs. It is after all a tried and true method of seperating materials based on their densities. HIV-1, HIV-2 and many SIVs have been "enriched" or seperated from the vast majority of other material obtained from cell cultures using this method, as have other viruses such as Rous Sarcoma Virus (also known as Avian Leukosis Virus). With the Perth group's further requirements, no virus with any morphological variation can be purified because they require that "all particles be IDENTICAL", and they place further restrictions on what has to be done to the virus before and after the centrifugation.

Peyton Rous began working with the group of avian retroviruses that became known as Rous Sarcoma Virus in 1909 and stopped in 1915, long before sucrose density gradient centrifugation was used by Crawford and Crawford to "purify" a sample of that virus to the Perth group's satisfaction in 1961.

Crawford LV, Crawford EM. (1961)
The Properties of Rous Sarcoma Virus Purified by Density Gradient Centrifugation.
Virology 13:227-232.

Likewise, there are hundreds of murine retroviruses that have been studied both before and after the 1973 publication by Francois Sinoussi (now Francois Barre-Sinoussi).

Sinoussi F, Mendiola L, Chermann JC, Jasmin C, Raynaud M. (1973)
Purification and Partial Differentiation of the Particles of Murine Sarcoma Virus (M. MSV) According to their Sedimentation Rates in Sucrose Density Gradients.
Spectra 4:237-243.

The M. MSV in this title refers to the Moloney strain of murine sarcoma virus, which is replication defective due to loss of viral genome regions which were replaced by the mos oncogene (a serine/threonine kinase family member). Most Moloney MSV strains thus require a helper virus to replicate. I would therefor suspect that the "pure virus" in the 1973 paper might be a mixture of both the helper and Moloney MSV viruses.

In the 1950-1980 time period, density gradient centrifugation would have been one of the best methods of seperating viral particles from most other constituents of a virus-infected cell culture. However, since 1980 many new methods have been developed which increase our ability to study viruses, particularly advances in monoclonal antibody productition for serological characterizations and molecular genetic techniques for even more detailed analyses. With centrifugation one can look at the strains of Moloney Murine Sarcoma virus that produce angiosarcomas and the strains of Moloney Murine Sarcoma Virus that produce rhabdomyosarcomas, and see that they look identical by electron microscopy. With serological techniques it might be possible to identify subtle differences between these strains. With infectious molecular clones, it becomes possible to disect the exact regions of the genome that contribute to the differences in tumor production of various strains, by making hybrids between the two strains of by introducing single genetic differences from one strain into the other.

It is useful to look at electron micrographs of viruses, and thousands of electron micrographs of HIV-1, HIV-2 and other lentiviruses have been produced in the last 20 years. However, for most research it is not necessary to have 100% "pure" virus. When the research does require "pure" virus, cloning of a complete viral genome into an infectious molecular clone is by far more accurate and informative than centifugation of whole virus from cell cultures.

In summary, viruses including retroviruses have been studied long before they were "purified" by gradient centrifugation, and they continue to be studied by many other methods besides gradient centrifugation. Centrifugation is useful, but it never was and is not now, a "requirement" for the study of any virus.

Competing interests:   None declared


Re: Re: HIV in South Africa 26 June 2003
Christopher S Tyler,
lay person
Provo, Utah 84604

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Re: Re: Re: HIV in South Africa

I believe Matthew Grove missunderstands what The Perth Group is saying with regard uni/bidirectional transmission.

He states: ...surely both partners in a male homosexual relationship can be either passive or active in any given sexual act, and may be active on one occasion and passive on another. So transmission is bidirectional.

The statement, "So transmission is bidirectional." is incorrect.

A bidirectionally transmitted std can be transmitted by the active partner, and also recieved FROM the passive partner PER SEXUAL ACT. In other words, if a male homosexual couple were 100 consistent in practicing position, that is, one partner always being a 'top' and the other always a 'bottom', either could become infected with a bidirectionally transmitted std without switching positions. The top could get it from the bottom, the bottom from the top.

For a unidirectionally transmitted agent, it would indeed require both partners to 'swap' and practice either role, i.e., being passive (bottom) AND being active (top).

In a study published in 1984 Robert Gallo wrote: "of eight different sex acts, seropositivity correlated only with receptive anal intercourse...and was **inversely correlated with insertive anal intercourse**.1

Therein lies the problem with what is said to be HIV, as it (a positive antibody test) behaves like a unidirectionally transmitted std. This presents great problems for places like Africa where it is assumed that heterosexual sex is the leading form of transmission. In other words, a man transmits it to a woman, or a woman transmits it to a man. Example of bidirectional transmition: A man who is married goes and has sex with an infected prostitute through vaginal sexual intercourse and she transmits it to him (passive to active). He comes home and transmits it to his wife through vaginal sexual intercourse (active to passive). In other words, the man in this scenario has not been the passive partner, yet has acquired the infection from the passive partner.

The Perth Group argues that this scenario is not backed up by published data and a reason they cite the much discussed Padien study:

Heterosexual Transmission of Human Immunodeficiency Virus (HIV) in Northern California; Results from a Ten-Year Study.

"Prospective results. We followed 175 HIV-discordant couples over time, for a total of approximately 282 couple-years of follow-up...At last follow-up, couples were much more likely to be abstinent or to use condoms consistently, and were much less likely to practice anal intercourse (p < 0.0005 for all). Nevertheless, only 75% reported consistent condom use in the 6 months prior to their final follow-up visit... no seroconversions occurred among exposed partners".

Considering the data above, how then do men become infected if HIV is only transmitted from the active partner (male) to the passive partner (female)? Are the majority of antibody positive males in Africa bisexual and practice frequent receptive anal intercourse? This, I believe, is one of many reasons The Perth Group consistently ask for the data proving that HIV is a heterosexually sexually transmitted disease. There are many other reasons for a positive antibody test, but by and large, the assumption is that it is because of infection by a retrovirus.

It is therefore an assumption that when a gay man becomes antibody positive (whatever that may mean in a given location) it is because he is infected with a virus. The Perth Group question this assumption of bidirectionality.

Chris Tyler

----- 1. Goedert JJ, Sarngadharan MG, Biggar RJ, et al. (1984). Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men. Lancet 2:711-6.

Competing interests:   None declared


We repeat: "Where is the proof for HIV purification by any method?" 26 June 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

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We repeat: "Where is the proof for HIV purification by any method?"

 

In his rapid response entitled "If it's Good Enough for RSV, Then it is Good Enough for HIV" (24 June 2003), Tony Floyd wrote:

"It has been posited [sic posted] above [presumably he is referring to our rapid response "Distinguishing between true and "official" HIV infection" 20 June 2003] that:

>an individual positive in New York City on the CDC criteria would not be positive in Sydney, Australia".

He comments "How extraordinary".  We agree.  It's the same virus and the same test.  Who would have ever thought travel or emigration could cure HIV infection?   The HIV antibody test is the only test in the history of medicine whose results have one meaning in one country or laboratory and another in another country or laboratory.   What is even more extraordinary is that this fact does not seem to worry the HIV experts.

 

Tony Floyd asks "Is there even one patient that you are aware of that this theory would apply to?"

This is not a theory.  It is a conclusion based on published data.  In a study entitled "False-Positive and Indeterminate Human Immunodeficiency Virus Test Results in Pregnant Women" published in 2000, the authors from the Departments of Paediatrics and Family Practice, University of Texas wrote:  "Under no circumstances should a patient be informed that she is infected unless both the ELISA and WB test results are positive...Testing for HIV is an emotional experience.  An HIV diagnosis may lead to depression, fear, anger and suicidal ideation.  Family, friends and community may ostracise infected people, and relationships with spouses or partners may be jeopardised.  An indeterminate result can cause the same problems if the physician misinterprets the result as being indicative of infection". (1)   They also pointed out that "It is possible for serum to be positive by one set of criteria and indeterminate by another" (1).

 

The study "Transmission of Human T-Cell Lymphotropic Virus Type III (HTLV-III) by Artificial Insemination by Donor" (2) is considered to be one of the first to prove infectivity by semen and has been quoted ever since in support of this claim.   The donor was considered as being positive on the basis of two bands (p41, p24) in the WB.   Four of the women were considered to have been infected, two on the presence of only one band (one woman had p41 and the other woman had p24), the other two women on the basis of two bands (p41 and p24).   At that time, the WB criteria was the presence of one band.   In 1987 the criteria were changed but nobody re-tested either these women or (to our knowledge) any other person deemed to be infected on the basis of the pre-1987 criteria.

 

Tony Floyd asks: "Is there anyone who, confirmed positive by all tests in New York, would then not be positive by the usual series of tests in Sydney?"

Answer:  What does Tony Floyd mean by "all tests"?  Both the US and Australia use the same testing algorithm.  The "usual series of tests" is a twice reactive ELISA followed by a positive Western blot.  There are many publications (Tony Floyd can look them up) in which a particular study states its criteria for a positive WB.  These include those of the CDC and interestingly that of the Multi-Center AIDS Cohort studies prior to the early 1990s.  In the latter one "strong" band was defined a positive WB.  Assuming some of the 5000 gay men tested in this study fulfilled this or the CDC criteria (the actual WB patterns are never published) then yes, an unknown number of individuals, who tested positive in the US, would not be positive in Australia.  (Has Tony Floyd ever wondered  how our National Reference Laboratory knows its criteria are proof of infection?  He could email the Director and report back to this forum http://www.nrl.gov.au).

Tony Floyd asks: "Or is it just a one-in-a-million hypothetical?   In which case it deserves as much attention as the plethora of other alternative AIDS arguments".

There is nothing hypothetical about these data and there is no need for a "plethora of" "alternative AIDS arguments".  Any argument about a retroviral theory of AIDS begins with whether or not there is such a retrovirus.

 

Tony Floyd also wrote:

"The attempted side-step of Brian Foley's question deserves attention:

What he asked was:

> If the Perth group believes that their method is valid for studying viruses, they should be able to name at least one virus which has been studied using their criteria. Where is the evidence that ANY virus has EVER been "purified" to their satisfaction?

This was in no way satisfied by merely providing references to a paper from 1961 about the Rous Sarcoma Virus and from 1973 about the Murine Sarcoma Virus."

 

Brian Foley asked for evidence and anyone (including Tony Floyd) upon reading the two references in our rapid response entitled "Where is the proof for HIV purification by any method?" (19 June 2003) would be "satisfied".

If Tony Floyd had read our rapid response (19 June 2003) carefully, he would have realized that there was no need to give any "indication" "as to why the papers might support the use of Density Gradient Centrifugation as a valid means of proving the existence any virus these days?"   As we pointed out in our rapid response (19 June 2003), "Density Gradient Centrifugation" has not been used only in 1961 and 1973 but has been the "preferred technique for purification of RTV" for at least the last 30 years.   This was the method used in the first studies (1983/1984)  (3), (4), (5) where HIV purification was claimed as well as in the last ones (1997) (6), (7).

 

Tony Floyd wrote:

"Why have even the two little known viruses mentioned not been associated with this separation technique in the last 30 years?"

 

The simple answer to this question is that there is no need for it any more.   The Rous Sarcoma Virus, as every virologist knows, is not a "little known" virus but (perhaps with the exception of "HIV") the best known retrovirus for which Nobel prizes have been awarded.  

 

Tony Floyd wrote:

"If you did cite the 1961 paper on Rous Sarcoma Virus as an example of a virus purified to your satisfaction, is it not ironic that RSV is a retrovirus very similar to HIV? In fact the fusion protein and an envelope glycoprotein precursor have been shown to be similar in both viruses(1)"

 

It appears that this time Tony Floyd did not ever bother to read the abstract but only the title of his reference 1 (8).   If he had read it, he would have realised that the abbreviation RSV in the title of his reference has nothing to do with the abbreviation RSV for the Rous Sarcoma Virus.   The first sentence of the abstract reads:

"The proteolytic cleavage sites of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 and the fusion protein of respiratory syncytial virus (RSV) show a sequence homology."

 

Respiratory syncytial virus (RSV) is not a retrovirus but a virus belonging to the family paramyxoviridae, genus pneumovirus.  

 

Tony Floyd wrote:

"If you are satisfied about the purification of RSV, then why is HIV so different?"

There has been no publications of electron micrographs proving purification of HIV.  

 

Tony Floyd wrote:

"Do you except [sic accept] that there might be a chance that all the infectious disease experts, virologists and vaccine developers around the world are working with a very real virus called HIV?"

All "the infectious disease experts, virologists and vaccine developers" are telling us that Montagnier proved the existence of a "real virus called HIV".   However, Montagnier acknowledges that to prove the existence of a retrovirus, it must be purified.   Since now Montagnier says that "I repeat, we did not purify" (9), why should we or for that matter anyone else including Tony Floyd accept the existence of a "very real virus called HIV"?

 

So the question still remains: "Where is the proof for HIV purification by any method?"

 

 

From the title of his rapid response entitled "Faster Progression to AIDS and Death Occurs in Those With Higher Levels of HIV VIRUS" (4 June 2003), Tony Floyd obviously believes that high "viral load" means high "levels of HIV virus".    Could he please give us the evidence which proves that high "viral load" means high "levels of HIV VIRUS".

 

 

In his rapid response entitled "Manipulations and misrepresentation of scientific facts only serve to fuel HIV/AIDS" (30 May 2003), Tony Floyd extensively quotes William Makgoba's statement made in the South African newspaper, THE SUNDAY INDEPENDENT, and finishes by saying: "Glad the truth is getting through where it matters most".

 

Below is our answer published in THE SUNDAY INDEPENDENT, June 15 2003:

 

"How to resolve Aids dispute once and for all

 

In his speech at the International Human Rights Network symposium in Switzerland ("Mixed signals on Aids eroding confidence", The Sunday Independent, May 25), Professor Malegapuru Makgoba put the question "A nutrition handbook, an African potato and some red herrings — are these really South Africa's responses to the HIV/Aids epidemic?" 

A better question necessitating an immediate answer is "Why are nevirapine and AZT monotherapy good enough treatment for South African women but not American women"?

Makgoba expressed the view "there has been a casting about for theories to contradict the orthodox scientific findings on HIV/Aids, such as the countenancing of discredited dissident theories". 

Scientific theories are discredited in scientific journals with scientific data. 

For over fifteen years we have questioned the HIV theory of AIDS and published alternative theories.  Yet to date no HIV experts have published any scientific data which discredit our views. 

Furthermore, they have done everything possible to prevent our publishing and continue to claim, as Makgoba reportedly said, "There is little doubt that HIV causes AIDS.  In contrast, there is no evidence that common African conditions such as poverty; malnutrition; and many chronic infectious diseases by themselves, singly or in combination, cause the characteristic immunodeficiency typical of Aids.", that is, "the progressive depletion of CD4+ cells".

It is a great pity Makgoba failed to consider the eminent HIV/AIDS expert Piot and his group writing in Lancet in 1984. "Tuberculosis, protein calorie malnutrition, and various parasitic diseases can all be associated with depression of cellular immunity." 

At the same time, similar views were expressed by other HIV/AIDS experts such as Clumeck, Biggar and Quinn.  As far back as 1987 Canadian researchers stressed that before the AIDS era it was known that "In TB as well as in lepromatous leprosy, an immunosuppressive state will frequently develop in the host. This state is characterised by T lymphopenia with a decreased number of T helper cells [T4 cells] and an inverted T-helper/T-suppressor cell ratio ...Immunosuppression induced by the infection with M.tuberculosis can persist for life, even when the TB is not progressive".  

The same researchers noted that TB was present "prior to infection with HIV [prior to the development of a positive antibody test] or development of overt AIDS" (Before 1987 TB was not an AIDS defining disease). 

In other words, the presence of TB leads to a decrease in T4 cells and the positive antibody test ("HIV infection") follows rather than precedes TB.  In 1994  Essex and his colleagues proved that mycobacterial infections lead to the appearance of a positive antibody test which HIV experts consider proof for HIV infection.  They concluded that "ELISA and WB results [the two antibody tests used to prove HIV infection] should be interpreted with caution when screening individuals infected with M. tuberculosis or other mycobacterial species", and that "ELISA and WB may not be sufficient for HIV diagnosis in AIDS-endemic areas of Central Africa where the prevalence of mycobacterial diseases is quite high".

According to a 1998 Lancet editorial, the developing world "bears more than 90% of the global burden of HIV infection" and "Tuberculosis (TB) is the leading cause of death worldwide among people with HIV".  Professor Abdool Karim has written that in South Africa "Clinically, pulmonary tuberculosis (TB) is the main presenting illness among HIV infected persons". 

If this is the case then the vast majority of cases of HIV/AIDS can be eliminated simply by eradicating TB.  This can only be achieved by abolishing poverty and its consequences. 

Could Makgoba please provide us with one single scientific study with evidence proving HIV is the cause of AIDS?  With no effort spared to date we have been unable to find such a study. 

Also could Makgoba cite one scientific study with the evidence which proves HIV has been isolated/purified and thus it exists.

According to Makgoba, "Scientific and political controversy over HIV/Aids in particular is also not new.  In the late 1980s, for example, French and American scientists were locked in ugly battles about who first isolated the HI virus... After detailed investigation and scrutiny of the scientific literature and laboratory notes, then presidents Ronald Reagan of the United States and Francois Mitterrand of France signed an agreement that credited Dr Robert Gallo and Dr Luc Montagnier as the co-discoverers of HIV". 

Indeed, Montagnier's group in 1983 and Gallo's group in 1984 claimed to have isolated HIV, that is, to have obtained the HIV particles separate from everything else, namely, to have purified the HIV virus.   In a 1997 the French investigative journalist Djamel Tahi interviewed Montagnier over his 1983 Science paper where he claimed to have discovered HIV.  After repeated questioning Montagnier gave the stunning response that in electron micrographs of what they called "purified virus", even after a "Roman effort" they could not find any particles with "the morphology typical of retroviruses". 

He added "I repeat we did not purify!"   When Montagnier was asked if Gallo isolated/purified HIV, he replied "Gallo?…I don't know if he really purified.  I don't believe so".

The lack of proof of HIV isolation/purification and thus of its existence by "the co-discoverers of HIV" led us to propose an isolation experiment at the July 2000 Presidential AIDS Advisory Panel Meeting in Johannesburg.  This was to be carried out jointly by the Perth Group and HIV experts from South Africa.  It was agreed by both sides including Makgoba that this experiment should be performed as proof for the existence of HIV is the most basic tenet of the HIV theory of AIDS. 

The cost of this experiment is insignificant compared to the amount the South African government spends on HIV/AIDS.  Since then, the HIV experts from South Africa and especially Makgoba have done everything possible to prevent this experiment being carried out.  Why?  Is this not the way to resolve the issue once and for all?" (10)

 

 

References:

(1)   Doran TI, Parra E. (2000). False-positive and indeterminate human immunodeficiency virus test results in pregnant women. Archives of Family Medicine 9:924-9.

(2)   Stewart, GJ, Cunningham, AL, Driscoll, GL, Tyler, JP P, Barr, JA, Gold, J Lamont, BJ (1985) Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor. Lancet  ii:581-585.

(3)   Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioun C, Rozenbaum W, Montagnier L  (1983) Isolation of a T-Lymphotrophic Retrovirus from a patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science 220:868-871.

(4)   Schupbach J, Popovic M, Gilden RV, Gonda, M. A., Sarngadharan, M. G., Gallo, R. C. (1984)  Serological analysis of a Subgroup of Human T-Lymphotrophic Retroviruses (HTLV-III) Associated with AIDS. Science 224:503-505.

(5)   Sarngadharan M, G., Popovic M, Bruch L. (1984)  Antibodies Reactive to Human T-Lymphotrophic Retroviruses (HTLV-III) in the Serum of Patients with AIDS. Science 224:506-508.

(6)   Bess JW Jr, Gorelick RJ, Bosche WJ, Henderson LE, Arthur LO. (1997)  Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virology  Mar 31;230(1):134-44.

(7)   Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ. (1997)  Cell Membrane Vesicles Are a Major Contaminant of Gradient-Enriched Human Immunodeficiency Virus Type-1 Preparations. Virology  230: 125-133

(8)   Streckert HJ, Werchau H. (1992)  Epitopes at the proteolytic cleavage sites of HIV-1-gp120 and RSV-F protein share a sequence homology: comparative studies with virus-induced and antipeptide antibodies.   Intervirology 34(1):30-7. PMID: 1385356

(9)   Tahi D. (1998)  Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 5:30-34

(10)          Mhlongo S, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, Fiala C, Papadopulos-Eleopulos E.  2003, How to resolve Aids dispute once and for all. The Sunday Independent June 15, p7.

 

 

Competing interests:   None declared


Re: Re: Where is the proof for HIV purification by any method? 27 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

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Re: Re: Re: Where is the proof for HIV purification by any method?

The Perth group stated:
"Barre-Sinoussi and Chermann, the principal and the 2nd author of the 1983 Montagnier et al paper who, in 1973, used it to purify the murine sarcoma virus and to obtain material which contained nothing else but particles with "No apparent differences in physical appearance" (1)"

In fact, this paper states on 240 in Results:
"the particles isolated under conditions of rate sedimentation considered [sic] mainly of virus particles and very little amounts of contaminating material."

Furthermore, in the Discussion on page 243, they correctly note that what they have purified or enriched is not a single virus, but a mixture of at least two species of viruses:
"It is known that stocks of MSV consist of at least two different viral particles, muringe leukemia viruses (MLV) and defective murine sarcoma viruses (MSV) (12)."

This is because the Moloney Murine Sarcoma Virus has had its envelope gene replaced by the c-mos protooncogene which encodes a serine/threonine kinase. Without an env gene, the Mo-MSV is defective and cannot infect cells unless it is packaged into virions in which the env protein is provided by a helper virus which in this case is the murine leukemia virus.

Rodent genomes contain dozens of copies of endogenous retroviruses, some of which are nearly identical to the Moloney Murine Leukemia Virus. In addition, there are dozens of exogenous rodent retroviruses such as the Friend, Kirsten, SL3 and Abelson murine leukemia viruses. Whether or not these are all truly "different" viruses, or just different isolates of the same virus, is an open question. The point I want to make is that Sinoussi et al. did get viral particles that looked identical to each other by electron microscopy, but without molecular clones, sequences, or serological profiles they could only take the word of the people they obtained their 78A rat fibroblasts from, that these particles were derived from the Moloney strain of MSV and not the Kirsten strain or some endogenous mouse or rat retrovirus that had become activated. All of these retroviruses look alike.

In the 1980s, when cloning and sequencing and other techniques became available, many of these exogenous and endogenous, defective and competent viruses were cloned and sequenced. With this new genomic information, it became clear why the Sarcoma viruses cause various sarcomas and require a helper virus. For example, the Moloney Murine Sarcoma virus has no env gene, it has been replaced by the c-mos gene (which is called the v-mos gene when it is in the virus genome).

The other example of 100% pure virus that the Perth group cites is a paper by Crawford and Crawford on Rous Sarcoma virus (now known to be one of several strains of the Avian Leukosis Virus
Bieth E, Darlix JL. Complete nucleotide sequence of a highly infectious avian leukosis virus. Nucleic Acids Res. 1992 Jan 25;20(2):367. PMID: 1311072 )
These authors used a culture of "high titer strain" of RSV given to them by Dr. H Rubin. Again, they had to take the word of the donor that this was indeed the high titer strain of a virus charachterized by Peyton Rous in the 1908 to 1915 time period and further passaged by Bryan and Moloney in the 1950s to create a "high titer strain". By electron microscopy, it looks like a retrovirus but there is no way to tell if it is RSV or some other avian retrovirus. Again, in this paper, the authors do not state that the virus preparations are 100% pure. In fact they state on page 229 "The third preparation was RSV from a tumor wich has been purified by density gradient centrifugation. Such preparations contain much nonviral material, and counts of physical particles are therefore less accurate." and "the preparation is homogeneous and little nonviral material is evedent". This is similar to preparations of HIV-1 or HIV-2 which have been electron micrographed: some preparations contain less cellular debris than others but a little cellular debris is inevitable in this type of preparation.

The Rous Sarcoma Virus paper also states "DNA was barely detectable in the preparation; it would be equivalent to 2 x 10^5 molecular weight units per particle if it were actually present in the virus." again showing that this was not 100% "pure" virus and nothing else.

I fail to see why these two papers which describe centrifugation of retroviruses are accepted by the Perth group as meeting all of their criteria for isolation and purification of a virus, when similar papers describing the same procedures carried out with HIV-1 or HIV-2 are dismissed. It is especially irritating to me that they like the Moloney Murine Sarcoma Virus paper even when the authors state that the prepared virus is a mixture of at least two different viruses; the Moloney MSV and its MLV helper virus.

Competing interests:   None declared


Re: Distinguishing between true and "official" HIV infection 27 June 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545

Send response to journal:
HIV infection

The Perth group asks:
"Do patients really play a role in interpreting their own tests?"

And my answer is that of course they do in most cases, and they always should. The patient always knows more about the patient's history than the doctor does. An accurate diagnosis depends on more than test results, it also requires putting those results into the context of the whole picture. For one example: A person with weight loss could have an eating disorder, could have a lack of money to buy food, could be on a diet, or could have any number of other reasons for experiencing weight loss. The doctor can't go back in time and observe the patient over the past 2 months and see what he or she ate. The patient has to be the one to help the doctor understand what the cause of the weight loss might be.

Likewise, for HIV antibody testing, the person being tested knows more about their history of sexual activities, IV drug use and needle sharing, and transfusions than the doctor does (unless the doctor was the same one who gave the person the transfusions and the person was unconscious and not told about the transfusions). I have heard horror stories from many people who were misdiagnosed because they either did not give the doctor full details pertaining to their condition, or they gave details but the doctor chose not to pay attention to them. In one such case, an attractive young woman employed in the fasion industry nearly died from a ruptured appendix because the doctor assumed the woman must be sexually promiscuous and that pelvic inflamatory disease was the cause of her pain. This doctor just could not believe that this woman was not sexually active and he also failed to believe her descriptions of the severity of the pain.

The Perth group claims that a Phair et al paper stated that one strong western blot band was "proof" of HIV infection.
Phair J, Jacobson L, Detals R, Rinaldo C, Saah A, Schrager L, et al.
Acquired Immune Deficiency Syndrome Occuring Within 5 Years of Infection with Human Immunodeficiency Virus Type-1: The Multicenter AIDS Cohort Study.
Journal of Acquired Immune Deficiency Syndromes 1992;5:490-496

They go on to question how many of these patients with only a single band were truly infected. My question would be "How many, and what percentage of the patients in this cohort actually had only one strong band?". It is my understanding that almost all HIV-infected people produce strong immunological responses to many HIV proteins during the course of their infection, and almost none (perhaps less than 2%?) produce an immunoglobulin response to only one of the HIV-1 proteins. Many denialists like to talk about the indeterminate test results. They fail to mention that almost all people who experience such results either:
1) go on to produce strong reactions to many HIV proteins at a later time point, indicating that they were recently infected prior to the indeterminate result and had not yet raised antibody responses to more HIV proteins. or
2) go on to a negative test or more indeterminate results, indicating that they are not producing more anti-HIV antibodies over time, and are therefor most likely not truly infected.

Also, I doubt that the Phair paper stated that a single western blot band was "proof" of HIV infection. A single band may have been all that was required for enrollment into the study, but scientists rarely speak of "proof" of anything.

Competing interests:   None declared


Re: Re: Re: HIV in South Africa 27 June 2003
Matthew L Grove,
Consultant Rheumatologist
NTGH, NE29 8NH

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Re: Re: Re: Re: HIV in South Africa

In response to Chris Tyler's posting of the 26/6/03

My contention with Dr. Papadopulos-Eleopulos was with regard to her statement that because HIV is most strongly associated with the act of passive anal intercourse, then

"Since the main and absolutely necessary property of sexually transmitted agents is bidirectionality, that is, transmission from the passive to the active partner and vice versa, this means HIV cannot be sexually transmitted."

This is of course true for a heterosexually transmitted STD. But not for one spreading through a homosexual community, where individuals may be either active or passive partners in sexual intercourse.

If bidirectional transmission is to be defined as transmission that can occur in either direction per sexual act, then I have indeed erred in my statement.

I should instead of taken issue with the idea that bidirectionality is "absolute and necessary" for a disease to spread through a male gay population, as multiple unidirectional transmission events could clearly account for spread. It is worth noting that in clearly acknowledged heterosexual bidirectionally transmissible STDs (the Perth group is not going to dispute the existence of Chlamydia or Gonorrhea I hope...?), sex is between one infected and one non-infected partner (who then becomes infected), ie the disease spreads by multiple unidirectional events. The only difference in this case is that they can be between either the active or passive partner, and the roles are fixed; the partner has no choice as to whether be active or passive.

I.e. A virus transmitted most effeciently by unprotected anal intercourse from active to passive partner could spread rapidly through a promiscuous gay population. I can't understand why Dr Papadopulos-Eleopulos would dispute this when it is clearly possible; such an organism would qualify as an STD.

The next issue Chris raises is how such a virus could spread through a heterosexual population when the Padian study (1) shows that heterosexual transmission does not occur.

The objections to the Padian study have been set out in detail above, but to briefly recap:

(a) The couples were selected to be discordant for HIV, ie were self selected to be inefficient infection transmitters. Whether this was due to poor virus secretion, late stage disease, HLA type, safe sex practice - whatever - this is selection bias. They knew that one of them was seropositive, and that they were in a study of HIV transmission, and they had access to information on the theory of HIV transmission and how to avoid it.

(b) 15% of couples chose to be abstinent; 75% used condoms consistently. Ie only 20% of couples were at risk, and these "inconsistently" used condoms. Anal sexual practices declined over the course of the trial. This shows that the couples involved in the study followed the advice available as to how to minimise risk.

The Padian study neither proves or disproves whether HIV can be heterosexually transmitted from female to male; it is insufficiently powered to do this and vulnerable to bias. The only solid conclusion that can be drawn is that if you find out that you are HIV +ve, and have probably been so for some time, and your wife is still HIV -ve (despite the fact that you have been having sex for an indeterminate period whilst you were HIV +ve), and you take on and follow safe sex practice, then you can carry on having sex with your wife because the risk of transmission appears to be very low. This is good news for couples who find themselves in this position ... but not grounds to say heterosexual sex is necessarily safe. Particularly if your partner carries another STD.

I am running short of time so will briefly address the last point, how HIV seropositivity appears to be spreading too rapidly in South Africa for heterosexual transmission to credibly be the only route. I find the arguments that another vector might be involved (dirty needles etc) quite convincing, and certainly worthy of serious study. I don't feel this is inconsistent with HIV positivity being caused by a blood borne (and occasionally sexually transmitted) retrovirus, though.

Regards

Matt Grove

(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15

Competing interests:   None declared


Re: We repeat: "Where is the proof for HIV purification by any method?" 30 June 2003
James Whitehead,
Disabled because of toxic prescribed "medicines" for "hiv".
London SW2 2 LA.,
Work with other "effected" people in trying to expose the "hiv/aids" myths

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We repeat: "Where is the proof for HIV purification by any method?" 26 June 2003

Eleni Papadopulos-Eleopulos, Biophysicist Department of Medical Physics, Royal Perth Hospital, Western Australia, Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso Send response to journal: Re: We repeat: "Where is the proof for HIV purification by any method?"

Email Eleni Papadopulos-Eleopulos, et al.: Barry.Page@health.wa.gov.au

We repeat: "Where is the proof for HIV purification by any method?"

In his rapid response entitled "If it's Good Enough for RSV, Then it is Good Enough for HIV" (24 June 2003), Tony Floyd wrote:

"It has been posited [sic posted] above [presumably he is referring to our rapid response "Distinguishing between true and "official" HIV infection" 20 June 2003] that:

>an individual positive in New York City on the CDC criteria would not be positive in Sydney, Australia".

He comments "How extraordinary". We agree. It's the same virus and the same test. Who would have ever thought travel or emigration could cure HIV infection? The HIV antibody test is the only test in the history of medicine whose results have one meaning in one country or laboratory and another in another country or laboratory. What is even more extraordinary is that this fact does not seem to worry the HIV experts.

Tony Floyd asks "Is there even one patient that you are aware of that this theory would apply to?"

This is not a theory. It is a conclusion based on published data. In a study entitled "False-Positive and Indeterminate Human Immunodeficiency Virus Test Results in Pregnant Women" published in 2000, the authors from the Departments of Paediatrics and Family Practice, University of Texas wrote: "Under no circumstances should a patient be informed that she is infected unless both the ELISA and WB test results are positive...Testing for HIV is an emotional experience. An HIV diagnosis may lead to depression, fear, anger and suicidal ideation. Family, friends and community may ostracise infected people, and relationships with spouses or partners may be jeopardised. An indeterminate result can cause the same problems if the physician misinterprets the result as being indicative of infection". (1) They also pointed out that "It is possible for serum to be positive by one set of criteria and indeterminate by another" (1).

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXx In reply to:

"Tony Floyd asks "Is there even one patient that you are aware of that this theory would apply to?"

( yes several members of the group I attend are having contradictory results to this very day ukhivtreatmentdiscussionforum@yahoo.co.uk) and is Mr Tony Floyd not aware of the following study .

1: Clin Diagn Lab Immunol 2002 Jan;9(1):160-3 Related Articles,Links

Indeterminate human immunodeficiency virus Western blot profiles in ethiopians with discordant screening-assay results.

Meles H, Wolday D, Fontanet A, Tsegaye A, Tilahun T, Aklilu M, Sanders E, De Wit TF.

Ethio-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia.

"Between 1996 and 2000, a total of 12,124 specimens were tested for HIV-1 antibodies. Overall, 1,437 (11.9%) were positive for HIV-1 antibody. Ninety-one ( approximately 0.8%) gave equivocal results because of discordant results among the various screening assays and indeterminate WB profiles by the American Red Cross (ARC) criteria. Most (30.4%) of these indeterminate WB results were due to p24 reactivity. However, 12 samples (13.2%) displayed reactivity to p24 and gp41 or to p24 and gp120/160 proteins (positive by Centers for Disease Control and Prevention [CDC] criteria).

Only two samples (2.2%) were reactive to both env glycoproteins gp41 and gp120/160 (positive by the World Health Organization [WHO] criteria).

Of 31 WB assays initially indeterminate by the ARC criteria and with follow-up samples, 29 (93.5%) became negative when retested subsequently while 2 (6.5%) remained indeterminate for more than a year and were thus considered negative.

Using CDC and WHO criteria, 6 (19.4%) and 2 (6.5%), respectively, of these WB assays would have been considered falsely positive. "

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

I have read rather alot of published studies that show that the different criteria's used to define a so-called "positive" Western Blot "hiv antibody test does have dramatic effects on the numbers being "diagnosed" and that it works both ways, vice verca "false-positive"/ "false-negative". Is 19.4% rare ? It is clear that these practices ( widley varing criteria's)represent scientific nonsense at its worst. Please remember that the above percentages represent real people being "diagnosed" or "mis-diagnosed" as the case really is.

Thats before we get onto to the question of how can a test kit (Western Blot "hiv" antibody test kit) be specific to "hiv" when upto 30% of so-called "negative" people have one, two or more supposedly "hiv" specific bands detectable on Western Blot "hiv" antibody test kits ? Does that not strongley indicate that the bands are not specific to "hiv" at all.

By the way the Western blot has been effectlively banned from use in diagnostic settings in England and Wales since 1992 by the UKPHLS. Dr Phillip Mortimors views on this are rather interesting.

Competing interests:   A British Subject "diagnosed" with "hiv" 15 years ago and "aids" in 1998, currently boycotting the NHS and all British doctors. Not sponsored by anybody.


Re: Re: Re: Re: HIV in South Africa 30 June 2003
Christopher S Tyler,
n/a
84604

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Re: Re: Re: Re: Re: HIV in South Africa

A few points regarding Matthew Grove's recent post.

Matthew L Grove wrote:

"I should instead of taken issue with the idea that bidirectionality is "absolute and necessary" for a disease to spread through a male gay population, as multiple unidirectional transmission events could clearly account for spread. "

I believe the issue here is, that in order for this putative microbe to ALSO account for the vast number of assumed infections in places like Africa and Thailand, it has to be bidirectional. The HIV hypothesis must explain why heterosexual sex is said to be the predominant mode of transmission in Africa but not in the West. We can't simply be content with 'multiple unidirectional transmission events' as an explanation for gay male infections and then let it drop there.

It is generally believed that HIV originated in Africa and is related to SIV, the 'monkey version' of HIV. Is SIV said to spread unidirectionally? If HIV mutated from SIV, why would nature select unidirectional transmission (i.e., most optimally through gay male anal intercourse) as the mode of transmission? After all, if a microbe doesn't spread, it's dead.

Matthew L Grove wrote: "It is worth noting that in clearly acknowledged heterosexual bidirectionally transmissible STDs..., sex is between one infected and one non-infected partner (who then becomes infected), ie the disease spreads by multiple unidirectional events."

No. This again is incorrect. If sex happens between one infected and one non-infected partner, (who then becomes infected), regardless of role, the disease spreads by one bidirectional event. That is, the uninfected partner can receive it whether in the active or passive role.

If a female is infected, she can be completely passive and still transmit a bidirectional std to the active partner. An active infected male can transmit the bidirectionally transmitted std to the passive female.

Thus, the definition is bidirectional because it can go either way per sex act.

Matthew Grove goes on to say:

"...HIV seropositivity appears to be spreading too rapidly in South Africa for heterosexual transmission to credibly be the only route. I find the arguments that another vector might be involved (dirty needles etc) quite convincing, and certainly worthy of serious study. I don't feel this is inconsistent with HIV positivity being caused by a blood borne (and occasionally sexually transmitted) retrovirus, though."

Again an assumption is made here. That there is actually 'transmission' occuring. When we speak of transmission, we're actually talking about a reactive antibody test, and so any discussion of a 'route of transmission' must take into account the nature of the tool used to determine 'transmission'.

In the case of the HIV antibody tests (ELISA and Western Blot), it is known that many agents and conditions can cause them to be reactive, some of which are endemic to areas such as South Africa. For instance, antibodies directed against mycobacterium (M. leprae, M. tuberculosis, M. avium-intracellulare) significantly cross-react with the HIV antibody tests, leading researchers such as Kashala and Essex to state, "ELISA and WB may not be sufficient for HIV diagnosis in AIDS-endemic areas of Central Africa where the prevalence of mycobacterial diseases is quite high";(1)

The Perth Group highlight these (and other) problems in an article within volume 13 of Current Medical Research and Opinion: Since antibodies to mannans, including those contained in the walls of all fungi (Candida albicans, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, including Pneumocystis carinii),(2-14) react with the "HIV proteins" then, as Essex and his colleagues (1) have pointed out for mycobacterial infection in Africa, one would expect the sera of all people infected with fungi and mycobacteria to cross-react with the "HIV-1 glycoproteins" as well as to cause "significant cross- reactivities with HIV-1 pol and gag proteins". (5)

Thus, it is necessary not to make an assumption that just because an antibody test is reactive that transmission of a retrovirus has taken place. Even something as simple as malnutrition will cause reactivity in the HIV tests.

With regard to the Padian study, it may be dismissed as flawed, but at the end of the day, it mirrors the lack of a spread of HIV/AIDS in the general heterosexual population in the United States and Europe (this in-spite of the 'every one at risk' dire predictions of the 80's and 90's). After 23 years, HIV/AIDS is still primarily confined to the original risk groups.

And what do we have to show for these 23 years of the HIV hypothesis?

We have flawed, non-specific, non-standardizerd, non-reproducible antibody tests. The general public are given assurance as to their high degree accuracy, and in whose name those who are unlucky enough to be found positive (pick your criteria) are given a death sentence (prognostication).

We have drugs like the failed chemotherapy agent AZT which was approved on the basis of fraudulent human trials. A drug that has been responsible for the agonizing death of many thousands. How many people knew to even ask their doctor if AZT was converted sufficiently into its active form, AZTTP, in order to have an antiretroviral effect? How many doctors were even aware that only a small fraction of AZT is triphosphorylated by cellular enzymes and thus can't possibly have an antiretroviral effect. How many people were told by their doctors that AZT would eat away the lining of their intestines giving them horrible stomach pain, destroy their muscle tissues and kill their bone marrow? No. We're told to trust our doctors and scientists.

And we have the protease inhibitors that have mamed and disfigured many more. Facial wasting, buffalo humps, extended bellies, increased heart disease, increased diabetes, stick-like limbs, destroyed livers. In fact, end organ liver failure is now the leading cause of death among those taking them. I would encourage every scientist, doctor, or student on this board to go on the cocktail for a year and then tell us how wonderful and lifesaving these drugs are; how they're extending lives and making people live longer.

On the other hand, the Perth Group offers an hypothesis that leads the way non-toxic, inexpensive, and health-building antioxidants. I know more than one man who has been able to rebuild their bodies with the help of their oxidative stress theory after having had their bodies ruined by the cocktail.

Why is the world so opposed to what they have to offer, when the HIV hypothesis so far has offered a death sentence (antibody tests), and poisons (AZT, Navirapine, etc.)?

Chris Tyler

1. Kashala O, Marlink R, Ilunga M, et al. (1994). Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. J. Infect. Dis. 169:296-304.

2. Ezekowitz RA, Williams DJ, Koziel H, et al. (1991). Uptake of Pneumocystis carinni mediated by the macrophage mannose receptor. Nature 351:155-158.

3. Hoffman OA, Standing JE, Limper AH. (193). Pneumocystis carinni stimulates tumor necrosis factor-alpha release from alveolar macrophages through a beta-glucan-mediated mechanism. J. Immunol. 150:3932-3940.

4. O?Riordan DM, Standing JE, Limper AH. (1995). Pneumocystis carinni glycoprotein A binds macrophage mannose receptors. Infect-Immun 63:779-784.

5. Eleni Papadopulos-Eleopulos, Valendar F.Turner, John M Papadimitriou, Gordon Stewart, and David Causer. HIV ANTIBODIES: FURTHER QUESTIONS AND A PLEA FOR CLARIFICATION. Current Medical Research and Opinion. Vol. 13: 627-634, 1997

Competing interests:   None declared


Does the Rous Sarcoma Virus and Moloney Murine Sarcoma Virus also therefore NOT EXIST??? 1 July 2003
Tony Floyd,
Medical Student
Newcastle University

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Re: Does the Rous Sarcoma Virus and Moloney Murine Sarcoma Virus also therefore NOT EXIST???

> and is Mr Tony Floyd not aware of the following study .

> 1: Clin Diagn Lab Immunol 2002 Jan;9(1):160-3 Related Articles,Links

It does more than just ring a bell. In fact I've already pointed out the fallacy of a previous attempt to use it: Doctor Meles. Yet another researcher incorrectly cited in support of alternative AIDS theories... (Response posted 13th March 2003.)

In short, only 31 out of the 1437 tested were found to be indeterminate. Discussing the breakdown of the 31 whilst ignoring the other 1406 and ignoring the conclusions of the authors themselves is not really helping anyone.

>Tony Floyd wrote:

>"It has been posited [sic posted] above

This is the second time I have been incorrectly chastised for pointing to what has been posited (as well as posted).

To 'posit' is to put forward as fact or as a basis for argument. To posit something is to base something on the truth of (a particular assumption) - ORIGIN C17: from L. posit-, ponere 'place'.(2)

I don't think recycling misrepresentation of Meles' paper will lead anywhere. What the Perth Group need to do is explain how the Crawford(3) and Sinoussi(4) papers have failed to measure up to their claims. In attempting to validate their insistence that HIV must be separated by density gradient centrifugation, they have pointed to two experiments where the viruses involved are also not 100% purified(5).

If similar viruses fail this test, does that mean that they also cease to exist?

References:

(1) Meles H, Wolday D, Fontanet A, Tsegaye A, Tilahun T, Aklilu M, Sanders E, De Wit TF. Indeterminate human immunodeficiency virus Western blot profiles in ethiopians with discordant screening-assay results. Clin Diagn Lab Immunol. 2002 Jan;9(1):160-3. [Abstract]

(2) "posit •v." The Concise Oxford Dictionary. Ed. Judy Pearsall. Oxford University Press, 2001. Oxford Reference Online. Oxford University Press. 27 June 2003 http://0-www.oxfordreference.com.newcutter.newcastle.edu.au:80/views/entry.html?subview="Main&entry=t23.043745"

(3) Crawford LV, Crawford EM. (1961) The Properties of Rous Sarcoma Virus Purified by Density Gradient Centrifugation. Virology 13:227-232.

(4) Sinoussi F, Mendiola L, Chermann JC, Jasmin C, Raynaud M. (1973) Purification and Partial Differentiation of the Particles of Murine Sarcoma Virus (M. MSV) According to their Sedimentation Rates in Sucrose Density Gradients. Spectra 4:237-243.

(5) Foley B. Re: Re: Where is the proof for HIV purification by any method? BMJ Response. 27th June 2003.

Competing interests:   None declared


Re: Re: We repeat: "Where is the proof for HIV purification by any method?" 1 July 2003
James Whitehead,
Treating myself.
London SW2 2 LA.

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: J Clin Microbiol 1991 Oct;29(10):2280-4 Related Articles,Links

Overall, 443 (22.2%) serum specimens were HIV-1 Western blot positive, 390 (19.5%) had indeterminate HIV-1 Western blot patterns, and no samples were HIV-2 Western blot positive. The sensitivity of the ELISAs ranged from 97.5 to 99.8%, and the specificity ranged from 51.7 to 98.4%.

By population group, the negative predictive value ranged from 97.1 to 100%, in contrast to the positive predictive value, which varied from 6.6 to 100%.

Furthermore, the high frequency of indeterminate Western blots for African sera emphasizes the continual need for improved confirmatory assays and interpretation criteria.

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1: J Clin Microbiol 1992 Mar;30(3):691-7 Related Articles,Links

When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively.

When the DuPont Western blot was interpreted in accordance with the manufacturer's instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate.

The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.

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1: J Formos Med Assoc 1994 Apr;93(4):283-8 Related Articles,Links

Follow-up investigation of indeterminate western blot results for antibody to human immunodeficiency virus type 1. According to the interpretation criteria for the anti-HIV Western blot test recommended by the Centers for Disease Control, 38 (4.2%) were Western blot-positive, 110 (12.1%) were Western blot-negative, and 763 (83.7%) were Western blot-indeterminate.

The most common band patterns of indeterminate Western blot results were antibodies to gag gene product only (667/763, 87.5%) which included p18 only (180, 23.6%), p18 plus others (521, 68.3%), p25 only (55, 7.2%), and p25 plus others (212, 27.8%).

Eighty-three individuals with indeterminate Western blot results were followed-up and new serum samples were collected. None of the follow-up samples became positive.

When band patterns changed, they usually did so within the specific category (either gag, pol, or env), such as a change from p18 to its precursor p55.

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James: Everytime there are more "indeterminates" (persons having one, two or more supposedly specific to "hiv" proteins/bands detectable/reactive on western blot "hiv" antibody test kits) and everytime the number of "indeterminates" change then of course the number of so-called "positives" and or so-called "negatives" changes as a direct effect.But there is no study ever to the best of my knowledge ever validating any of these test kits using "hiv" itself, always indirect markers, other antibody test kits, algo rythams, as for Positive Predictive Value and Negative predictive Value (PPV/NPV) as also being complete unobjective scientific nonsense. I am afraid that I must also disagree, I do not think that many of the "confirmatory" tests, testing procedures, "interpretations", "prolonged -longed incubations", dilutions, heat treating, pokeweed mitogen, EDTA are objective or scientific. A simplified version of "PPV/NPV" is guilty of crime if considered to be from a high risk area/group or not guilty of a crime if considered to be from a low risk area/group.

Competing interests:   User of NAC, Undenurtured whey protein, alpha lipoic acid,anti oxidents,l glutamine,Acetyl l carnitine (when I can afford it) herbs, diet doing an awfull lot better now.No provisions on NH "s". No CHOICES.


H2O toxicity 2 July 2003
Peter J Flegg,
Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: H2O toxicity

Having read Mr Tyler's diatribe against the apparently lethal effects of HIV medication, I was reminded of the man who refused to drink any water after hearing that someone had died from drowning.

The online BMJ should be a forum for coherent, rational and evidence- based debate, not untruths dressed up in tabloid journalese.

Competing interests:   None declared


Re: H2O toxicity 2 July 2003
Christopher S Tyler,
n/a
84604

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Re: Re: H2O toxicity

As I stated in my 'diatribe', I invite Peter Flegg to go ahead and partake of this innocuous 'water', that is, go on these drugs for a year and then report back to the forum. Could he please provide evidence that treating people deemed infected with HIV with a failed chemotherapy agent, AZT, is warranted considering;

1) AZT doesn't triphosphorylate in vivo to nearly sufficient levels in order to have an antiretrovial effect;

2) The well known toxicities of AZT including anemia (bone marrow destruction), mitochondrial dysfunction, and genetic mutations.

Considering the pressure for governments of countries like South Africa to provide AZT and the like to its people, I believe a discussion of the dangers of such 'medications' is warranted on this forum.

To quote from "A Critical Analysis of the Pharmacology of AZT and its Use in AIDS", the Perth Group writes:

Although AZT is not efficiently triphosphorylated it is very efficiently mono-phosphorylated. The mono-phosphorylation of AZT could act as an inhibitor of phosphorylation of cellular constituents, including cellular nucleotides. Indeed, in 1986 Furman and his associates showed that, in vitro, exposure of cells to 50mM of AZT for 72 h led to a decrease of approximately 95% in dTTP and dCTP and a decrease of approximately 63% in dGTP. This decrease in the triphosphorylated nucleotides in its turn will lead to decreased cellular DNA synthesis. In the presence of such a profound, global reduction in the concentrations of the naturally occuring nucleotides, one would predict untoward effects on many tissues, especially those with the most rapid cellular turnover including the gut and the bone marrow. Indeed, 'a characteristic feature of zidovudine therapy is an elevated MCV [mean corpuscular red cell volume]' (54), and 'The antiviral agent zidovudine (AZT), used for treating the human immunodeficiency virus (HIV), often causes severe megaloblastic anemia' (55), anaemia 'caused by impaired DNA synthesis' (55).

Current Medical Research and Opinion Vol. 15: Supplement, 1999 http://www.virusmyth.com/aids/data/epazt2.htm

Please find below a truncated list of quotes from the medical literature regarding problems with AZT. This list is by no means exhaustive.

Chris Tyler

<b>Bone Marrow Suppression/Anemia:</B>

"nearly one half of patients treated with AZT for [HIV]-associated disease develop transfusion-dependent anaemia due to bone marrow depression" Dainiak N et al. 3'-Azido-3'-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. British Journal of Haematology. 1988;69:299-304. ----------------------------

"more than half of all AIDS patients may not benefit from the drug because it is more toxic for them than their AIDS infection. The most serious side effect of AZT is to suppress the bone marrow, leaving patients highly vulnerable to bacterial infections" Kolata G. Imminent marketing of AZT raises problems; marrow suppression hampers AZT use in AIDS victims. Science. 1987 Mar 20;235:1462-3. ------------------------------

"We found that 78.2% of the patients with mild or severe anaemia at baseline had received zidovudine [AZT]" Mocroft A et al. Anaemia is an independent predictive marker for clinical prognosis of HIV-infected patients from across Europe. AIDS. 1999;13:943-50. -------------------------

"While effective drug therapy is continued in zidovudine[AZT]-treated HIV-infected patients…PROCRIT Reduces Transfusion Requirements and Helps Lift the Burden of Anemia." Advertisement for PROCRIT. 1997.

<b>Mitochondrial Dysfunction</b>

"typical mitochondrial myopathy has been reported to be expressed among many patients with AIDS treated with long-term azidothymidine (AZT) therapy" and "for AIDS patients, it is urgently necessary to develop a remedy substituting this toxic substance, AZT" Hayakawa M et al. Massive conversion of guanosine to 8-hydroxy- guanosine in mouse liver mitochondrial DNA by administration of azidothymidine. Biochem Biophys Res Commun. 1991;176:87-93. ----------------------

"A severe proximal myopathy, predominantly affecting the legs, seems to be a significant complication of long-term zidovudine therapy, even at reduced doses; it affected 18% of our patients who had received treatment for more than 200 days. Other drugs could not be implicated. The pathogenesis is obscure; the myopathy resolves on cessation of zidovudine, but not on dose-reduction, though there is then a risk of rebound encephalitis." Helbert M et al. Zidovudine-associated myopathy. Lancet. 1988 Sep 17;2:689-90. -----------------------

"Long term therapy with [AZT] can induce a toxic myopathy associated with mitochondrial changes" Chariot P, Gherardi R. Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy. Neuro Muscul Disorders. 1991;1:357-363. ----------------------

<b>Increased Risk of Sickness and Death</b>

"Extended follow-up of patients in one [AZT] trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early...where is the evidence that for a patient with a CD4 count of 450 cells per cubic millimeter and a low plasma viral level, it would not be better to wait before initiating therapy?...In 1990...a patient with a CD4 count of 450 cells per cubic millimeter would have been advised to start monotherapy with zidovudine. We now tell such a patient that, in fact, follow-up data for up to 4.5 years since that time have shown no survival benefit" Phillips AN, Smith GD et al. Viral load and combination therapy for Human Immunodeficiency Virus. N Engl J Med. 1997 Mar 27;336(13) -------------------------

"The mortality rate was significantly higher among [a group of 1372] patients who had received antiretroviral therapy [principally AZT] before enrollment in the clinic" Chaisson RE, Keruly JC, Moore RD. Sex, race, drug use and progression of human immunodeficiency virus disease. N Engl J Med. 1995;333(12):751-6. -------------------

"Only 38% of the HLP [Healthy long-term positives] had ever used zidovudine [AZT] or other nucleoside analogues, compared with 94% of the progressors." Buchbinder S et al. Long-term HIV-1 infection without immunologic progression. AIDS. 1994;8:1123. --------------------------

"after starting antiretroviral treatment...the estimated probability of developing lymphoma ...by 36 months, [was] 46.4% (CI, 19.6% to 75.5%)...a direct role of therapy itself cannot be totally discounted...Zidovudine can act as a mutagen" Pluda JM et al. Development of non-Hodgkin lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy. Ann Intern Med. 1990 Aug 15;113(4):276-82.

----------------- "The Concorde trial showed no difference in the survival rates for symptom-free HIV-positive individuals between those given immediate and those given deferred zidovudine, and Chaisson et al found previous use of zidovudine to be a negative indicator, with an increase in the risk ratio for death or disease progression of 1.7" Scott WF. The Delta Trial. Lancet. 1996;348(9036):1238.

<b>General problems</b>

"Perinatal treatment with 3'-azido-3'-deoxythymidine (AZT) has been found to reduce the rate of maternal-infant transmission of HIV; however, AZT is clastogenic at therapeutic doses in adult patients and induces cancers in the offspring of mice treated in utero. The purpose of the present study was to investigate the mutagenicity of AZT at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus of the human lymphoblastoid cell line, TK6, following in vitro exposures. ..There was a significant increase over background in hprt Mfs [mutation frequencies] in TK6 cells exposed to 300mM AZT for 3 days (1.8-fold increase). In cells exposed for 6 days, there was a decrease in...cell survival. ..These preliminary results indicate that AZT treatment is mutagenic and produces large deletions in human cells."

Sussman HE et al. Mutagenicity of AZT in the human lymphoblastoid cell line, TK6. 2nd National AIDS Malignancy Conference. 1998 Apr;94. ----------------------

Competing interests:   None declared


A plea for the references on HIV purification 3 July 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papdimitriou, Barry Page, David Causer, Helman Alfonso

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Re: A plea for the references on HIV purification

A plea for the references on HIV purification

According to the Oxford dictionary, to "purify" means to "clear of foreign elements". There are several reasons why it is necessary to purify a retrovirus. These reasons include the need to characterise the viral proteins and viral RNA. As Montagnier pointed out: "It is necessary to do that" (1). Unless this is done, it is not possible to claim the existence of viral proteins and a viral genome and talk of "cloning of a complete viral genome into an infectious molecular clone" as Brian Foley wrote in his rapid response entitled "Re: Where is the proof for HIV purification by any method?" (26 June 2003).

Brian Foley wrote "With the Perth group's further requirements, no virus with any morphological variation can be purified because they require that "all particles be IDENTICAL", and they place further restrictions on what has to be done to the virus before and after the centrifugation."

Let us be very clear on this matter. These "requirements" and "restrictions" which are really a common sense approach were formulated by virologists such as Barre-Sinoussi, Chermann, (2) Crawford, (3) Toplin (4) and are consequences of the very nature of retroviruses. Since retrovirus-like particles are ubiquitous in nature it follows you must prove that the particles in question: (i) are indeed viral particles, that is, that they are infectious; (ii) have reverse transcriptase and RNA but not DNA; (iii) they represent a unique retrovirus, that is, they must have unique RNA and proteins.

Brian Foley wrote: "Of course thousands of HIV researchers have used sucrose and other density gradient preparations of HIV-1…It is after all a tried and true method of separating materials based on their densities. HIV-1… have been "enriched" or separated from the vast majority of other material obtained from cell cultures using this method…" This is just what we have been after for more than the past 15 years!!! Could Brian Foley or anyone else please give us a few of the "thousands" of references where HIV-1 has been separated "from the vast majority of other material", in other words, purified?

Brian Foley wrote: "Peyton Rous began working with the group of avian retroviruses that became known as Rous Sarcoma Virus in 1909 and stopped in 1915, long before sucrose density gradient centrifugation was used…" In a subsequent rapid response "Re: Re: Where is the proof for HIV purification by any method?" (27 June 2003), Brian Foley wrote: "…a virus [the Rous Sarcoma Virus] characterized by Peyton Rous in the 1908 to 1915 time period…" It was in 1911 when Peyton Rous induced malignancy in chickens by injections of cell-free filtrates obtained from a muscle tumour. Rous did not characterize a virus and in fact, Rous only suggested that the causative agent was a virus. Indeed, Rous warned, "The first tendency will be to regard the self-perpetuating agent active in this sarcoma of the fowl as a minute parasitic organism. Analogy with several infectious diseases of man and the lower animals, caused by ultramicroscopic organisms, gives support to this view of the findings, and at present work is being directed to its experimental verification. But an agency of another sort is not out of the question. It is conceivable that a chemical stimulant, elaborated by the neoplastic cells, might cause the tumour in another host and bring about in consequence a further production of the same stimulant." (5) Decades after 1911, Rous was reported to have said "that he had never said it was a virus, carefully using the term 'tumour agent'".(6)

Brian Foley wrote: "…since 1980 many new methods have been developed which increase our ability to study viruses, particularly advances in monoclonal antibody production for serological characterizations and molecular genetic techniques for even more detailed analyses… When research does require "pure" virus, cloning of a complete viral genome into an infectious molecular clone is by far more accurate and informative than centrifugation of whole virus from cell cultures."

We agree that genetic techniques and monoclonal antibodies (not forgetting that like all other antibodies, monoclonal antibodies may cross -react) can be used for more detailed analyses of retroviruses. However, this cannot be done unless one first obtains the viral proteins (antigens) and the viral genome and these can only be obtained by purifying the virus. It appears Brian Foley either has not read or has forgotten the comments we made regarding the cloning of HIV or the HIV genome in our rapid response entitled "A simple request from the Perth Group" (5 June 2003). So we will repeat them.

To obtain a molecular clone means to produce an identical copy of a DNA fragment. At present this can be achieved for any such molecule without undue difficulty. However, to clone an object such as a virus, bacterium or an animal is a different matter. It requires three main steps. For example, to clone Dolly the sheep, it was absolutely necessary for the researchers to obtain the genome from a sheep's cell, introduce it into the ova and lastly prove the birth of a sheep. Similarly, to claim proof of HIV cloning it is absolutely necessary to obtain the HIV RNA from HIV particles, introduce it (or its cDNA) into a suitable cell and ultimately prove the appearance of similar HIV particles. In our view at present, the only way to obtain the HIV genome is first to obtain material which consists of purified HIV particles or at least a material which does not contain any impurities with nucleic acids.

In 1997 some of the best known HIV researchers wrote: "Virus to be used for biochemical and serological analyses or as an immunogen is frequently prepared by centrifugation through sucrose gradients. The fractions containing viral antigen and/or infectivity are considered to contain a population of relatively pure virus particle." This is preceded by: "However, in none of the studies…has the purity of the virus preparation been verified." (7) In other words, at least up to 1997, the HIV genome was obtained from a "pure" HIV whose contents were unknown (except Montagnier's "purified" virus which did not even have particles with "the morphology typical of retroviruses".(1)) This means that at least up to 1997, nobody could claim proof of either HIV cloning or molecular HIV cloning. Perhaps Brian Foley has information to the contrary. If so, we implore him to provide a few references that prove: (i) the molecules used in "cloning of a complete viral [HIV] genome" originated from HIV particles; (ii) cloning of HIV; (iii) the HIV "Genetic Sequences" in his databases originated from HIV particles.

In his rapid response "Re: Re: Where is the proof for HIV purification by any method?" (27 June 2003), referring to the Barre- Sinoussi 1973 paper (2), Brian Foley wrote: "In fact, this paper states on 240 in Results: "the particles isolated under conditions of rate sedimentation considered [sic] mainly of virus particles and very little amounts of contaminating material." This quote does not refer to the electron micrographs obtained from the density gradients bands for which the authors wrote: "From the electron- photo micrographs…these fractions contained mainly typical spherical C- type particles. No apparent differences in physical appearance could be discerned among the viral particles in these regions." (2)

Brian Foley wrote: "The point I want to make is that Sinoussi et al. did get viral particles that looked identical to each other by electron microscopy, but without molecular clones, sequences, or serological profiles they could only take the word of the people they obtained their 78A rat fibroblasts from, that these particles were derived from the Moloney strain or MSV and not the Kirsten strain or some endogenous mouse or rat retrovirus that had become activated. All of these retroviruses look alike."

We are glad that Foley agrees Sinoussi et al. produced an electron micrograph which showed only "viral particles that looked identical to each other". Their scope was not to characterize the MSV. It is only when you want to prove the existence of a unique new retrovirus that you must proceed with all the other steps, namely, "molecular clones, sequences, or serological profiles" which are the requirements to characterize the viral particles as being unique, steps which can only follow and not precede purification.

Referring to the Crawford et al. 1961 paper (3), Brian Foley wrote: "Again, in this paper, the authors do not state that the virus preparations are 100% pure. In fact they state on page 229 "The third preparation was RSV from a tumour which has been purified by density gradient centrifugation. Such preparations contain much nonviral material, and counts of physical particles are therefore less accurate."

Since the third preparation was taken from a tumour, we can expect nonviral particles to be present. However, regarding the first and second preparations which were obtained from culture, the authors wrote: "Figures 1 and 2 are electron micrographs of a preparation of purified RSV after fixation and sectioning. It will be seen that the preparation is homogeneous and little nonviral material is evident."(3)

Brian Foley wrote: "The Rous Sarcoma Virus paper also states "DNA was barely detectable in the preparation; it would be equivalent to 2 x 10^5 molecular weights units per particle if it were actually present in the virus."

This was an initial observation by the authors who then went on further and stated: "Table 3 gives the results obtained for the base composition of RSV…In the initial separation by paper chromatography any DNA present would remain at the origin. No ultraviolet-absorbing material was detected in this position, confirming the virtual absence of DNA in the RSV preparation."(3)

So perhaps Brian Foley may reconsider his conclusion: "Again showing that this was not 100% "pure" virus and nothing else."

Brian Foley wrote: "I fail to see why these two papers which describe centrifugation of retroviruses are accepted by the Perth group as meeting all of their criteria for isolation and purification of a virus, when similar papers describing the same procedures carried out with HIV-1 or HIV-2 are dismissed. It is especially irritating to me that they like the Moloney Murine Sarcoma Virus paper even when the authors state that the prepared virus is a mixture of at least two different viruses; the Moloney MSV and its helper MLV virus."

Our criteria cover not only isolation/purification but also characterization of the virus. We would be grateful if Brian Foley could provide us with references showing HIV-1 preparations in which "No apparent differences in physical appearance could be discerned among the viral particles in these regions" as Sinoussi et al. did and with "a high degree of homogeneity" and "virtual absence of DNA"as Crawford et al did. Then and only then can we proceed and characterize the viral particles.

In fact Brian Foley gave his rapid responses the titles: "Re: Where is the proof for HIV purification by any method?" and "Re: Re: Where is the proof for HIV purification by any method?" but has failed to give us any published proof. So we repeat "Where is the proof for HIV purification by any method?" That is, give us the published references.

References

(1) Tahi D. Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998 5:30-34

(2) Sinoussi F, Mendiola L, Chermann JC, Jasmin C, Raynaud M. (1973) Purification and Partial Differentiation of the Particles of Murine Sarcoma Virus (M. MSV) According to their Sedimentation Rates in Sucrose Density Gradients. Spectra 4:237-243.

(3) Crawford LV, Crawford EM. (1961) The Properties of Rous Sarcoma Virus Purified by Density Gradient Centrifugation. Virology 13:227-232.

(4) Toplin I, Sottong P. (1972) Large-Volume Purification of Tumor Viruses by Use of Zonal Centrifuges. Applied Microbiology 23 (5): 1010-1014.

(5) Rous PA. (1911) Sarcoma of the Fowl transmissible by an agent separable from the tumor cells. J Exp Med 13: 397-411

(6) Broxmeyer L. (2003) Medical Hypotheses 60 (5):671-688

(7) Gluschankof P, Mondor I, Gelderblom HR, Sattentau QJ. (1997) Cell Membrane Vesicles Are a Major Contaminant of Gradient-Enriched Human Immunodeficiency Virus Type-1 Preparations. Virology 230: 125-133

Competing interests:   None declared


Re: H2O toxicity 4 July 2003
Carl Williams,
Lay person
TQ11 0LQ

Send response to journal:
Re: Re: H2O toxicity

Dear Editor,  

I agree with Peter Flegg's remarks that the online BMJ should be a forum for coherent, rational and evidence- based debate, not untruths dressed up in tabloid journalese.  Unfortunately, in the case of Highly Active Anti-Retroviral Therapy (HAART), it is impossible to have an evidence- based debate because to date, there have been no published properly controlled studies to assess if HAART confers any clinical benefits whatsoever - i.e. at least 2 randomised, double-blinded placebo controlled studies, where on the one arm is HAART and on the other is a true placebo, (not AZT, or other combinations of drugs).

In this context I find Peter Flegg's preceding remarks comparing Christopher Tyler's criticisms of HIV medications analogous to "the man who refused to drink water after hearing that someone had died from drowning" ridiculous, and (at the risk of being charged with sententiousness) in the context of this discussion forum quite frankly offensive.   

Christopher Tyler is clearly not trying to argue that individuals diagnosed HIV positive should refuse to take antiretroviral therapy because someone has drowned in a vat of AZT.  He states what is self-evident; that the currently available anti-HIV regimes continue to have high levels of toxicity, that over time there are horrendous side effects from taking them, and that according to research the primary cause of death amongst those who take ARV is liver failure, not AIDS.  

I can only assume Peter Flegg's work as a physician is unconnected to the field of HIV / AIDS because to imply that HIV medications are not highly problematic and without seriously high levels of toxicity is to enter into the realm of incoherence, irrationalness and non- evidence / untruths that he states has no place on this forum.  

For Peter Flegg's benefit (and anyone else who is unaware of the problems associated with antiretroviral medications) the following comments on the utility of ARV are from physicians who do work in the field of HIV /AIDS.

"…But none of these arguments would have been sufficient to deter many clinicians and patients from supporting early treatment, had the toxicity of HAART not become painfully apparent. Initially there were reports of diabetes, then came fat redistribution, then hyperlipidemia, then…[15] The list seems to be growing by the week.   The sad truth is that this life-saving therapy is in fact very toxic for a significant proportion of patients. The indisputable benefits of therapy in patients with advanced disease are not so clear in asymptomatic patients with high CD4+ cell counts. Mathias Egger[16] has suggested that at certain CD4+ cell-count levels it appears more likely that therapy hurts patients rather than helps them. For patients whose high CD4+ counts do not place them at imminent danger of HIV disease progression, the high risk of developing drug resistance (at least 40% after 2-3 years), the high frequency of significant toxicity, the increased cardiovascular risk, and the difficulties with adherence make the price paid for an "undetectable viral load" too high to justify."  

Source: Medscape HIV/AIDS  

Practical Issues in Antiretroviral Therapy When Should Antiretroviral Therapy Be Initiated? Early Initiation of Antiretroviral Therapy: The Case for Caution  

Pablo Tebas, MD

Dr. Brian Conway responds:

In 1996, the availability of highly active antiretroviral therapy (HAART) revolutionized the model of care for HIV infection. Indeed, it was hypothesized that the consistent use of such therapy could lead to a cure for this condition in as little as three years. Subsequent research has shown this model to be incorrect. In addition, long-term use of HAART has now been associated with significant metabolic abnormalities, which could lead to unintended morbidity. In some patients, this morbidity could be worse than what one could expect from the progression of HIV-associated immune disease itself over the same period of time.

Source: Ask the Experts
February 25, 2003

The following study also covers the issue of the clinical reality of taking ARV.

In a cross-sectional, observational study of 1160 patients who were receiving potent antiretroviral treatment the authors make the following remarks: "In the outpatient population included in this analysis, more than two thirds of patients presented one or more clinical or laboratory adverse events which could have been due to antiretroviral treatment."

Prevalence of adverse events associated with potent antiretroviral treatment:

Swiss HIV Cohort Study  

Part of Christopher Tyler's 'diatribe' that so vexed Peter Flegg were comments concerning the side effects of taking Protease inhibitors.  If Peter Flegg is not aware of the particular problems associated with taking PI's, he might care to look at the following.

"It is possible that protease inhibitors increase the risk of artery disease not only by boosting levels of triglycerides and cholesterol but also by acting directly on macrophages, Hui notes in an editorial that accompanies the study."

Reuters Health, February 4 2003

SOURCE: Journal of Clinical Investigation 2003;111:317-318,389-397

If Peter Flegg, or anyone else is under any doubt as to the legitimacy of Christopher Tyler's remarks concerning the ability of AZT to triphosphorylate in vivo, or AZT's ability to destroy muscle tissue and bone marrow, they might care to read South African Barrister Anthony Brink's claim for compensation against GlaxoSmithKline, manufacturers of AZT on behalf of Annet Hayman.  The following except covers the points Christopher Tyler makes about the effects of taking AZT

 TREATMENT OF THE DECEASED WITH AZT AND HIS DEMISE  

10.1 Towards the end of July 1997 and in Ladysmith, KwaZulu-Natal, the deceased commenced a month's course of AZT, together with a related drug, 3TC, at daily oral doses of 600mg and 300mg respectively, which had been prescribed to him following an HIV- positive diagnosis based on reactive antibody tests for HIV, and a low CD4+ cell count.  

10.2 When he commenced treatment with AZT, the deceased weighed 68kg, was not sick and presented with no symptoms of any illness.

10.3 The AZT treatment immediately made the deceased very ill, causing intractable diarrhoea and vomiting, intense headache, profound lassitude, anaemia, muscle weakness with cramps and pain, and progressive weight loss.

10.4 The severity of the drug's ill effects experienced by the deceased led him to lower the dose of his own accord and thereby extend the month's course of treatment over about two months.  

10.5 The deceased declined a second course of AZT, but the ill effects of the first course failed to resolve.

10.6 The deceased was subsequently hospitalised on three occasions for uncontrollable diarrhoea and vomiting without any specific infectious aetiological agent being detected on pathological investigation, continued to suffer profound fatigue, continued to suffer muscular weakness and deterioration, and lose muscle mass and body weight, and finally died in Ladysmith, KwaZulu-Natal on 8 June 1998 weighing 42 kg.  

10.7 The deceased died as a direct result of the cellular toxicity of AZT.

Yours,
Carl Williams

Competing interests:   None declared


Re: A plea for the references on HIV purification 3 July 2003
Brian T Foley,
HIV researcher
Los Alamos National Lab Los Alamos NM USA 87545

Send response to journal:
Re: Re: A plea for the references on HIV purification

Recent papers:

Regier DA, Desrosiers RC.
The complete nucleotide sequence of a pathogenic molecular
clone of simian immunodeficiency virus.
AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221-31.
PMID: 2078405

Takeuchi H, Suzuki Y, Tatsumi M, Hoshino H, Daar ES,
Koyanagi Y.
Isolation and characterization of an infectious HIV type 1
molecular clone from a patient with primary infection.
AIDS Res Hum Retroviruses. 2002 Oct 10;18(15):1127-33.
PMID: 12402946

Mochizuki N, Otsuka N, Matsuo K, Shiino T, Kojima A, Kurata
T, Sakai K, Yamamoto N, Isomura S, Dhole TN, Takebe Y,
Matsuda M, Tatsumi M.
An infectious DNA clone of HIV type 1 subtype C.
AIDS Res Hum Retroviruses. 1999 Sep 20;15(14):1321-4.
PMID: 10505681

Novelli P, Vella C, Oxford J, Daniels RS.
Construction and characterization of a full-length HIV-1(92UG001)
subtype D infectious molecular clone.
AIDS Res Hum Retroviruses. 2002 Jan 1;18(1):85-8.
PMID: 11804560

Ndung'u T, Renjifo B, Novitsky VA, McLane MF, Gaolekwe S,
Essex M.
Molecular cloning and biological characterization of
full-length HIV-1 subtype C from Botswana.
Virology. 2000 Dec 20;278(2):390-9.
PMID: 11118362

Ndung'u T, Renjifo B, Essex M.
Construction and analysis of an infectious human
Immunodeficiency virus type 1 subtype C molecular clone.
J Virol. 2001 Jun;75(11):4964-72.
PMID: 11333875

Takahoko M, Tobiume M, Ishikawa K, Ampofo W, Yamamoto N,
Matsuda M, Tatsumi M.
Infectious DNA clone of HIV type 1 A/G recombinant
(CRF02_AG) replicable in peripheral blood mononuclear cells.
AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1083-7.
PMID: 11485626

Earlier papers:

Adachi A, Ono N, Sakai H, Ogawa K, Shibata R, Kiyomasu T,
Masuike H, Ueda S.
Generation and characterization of the human
immunodeficiency virus type 1 mutants.
Arch Virol. 1991;117(1-2):45-58.
PMID: 1706590

Kuwata T, Igarashi T, Ido E, Jin M, Mizuno A, Chen J,
Hayami M.
Construction of human immunodeficiency virus 1/simian
immunodeficiency virus strain mac chimeric viruses
having vpr and/or nef of different parental origins and their in vitro and in vivo replication.
J Gen Virol. 1995 Sep;76 ( Pt 9):2181-91.
PMID: 7561755

Collman R, Balliet JW, Gregory SA, Friedman H, Kolson DL,
Nathanson N, Srinivasan A.
An infectious molecular clone of an unusual
macrophage-tropic and highly cytopathic strain of human
immunodeficiency virus type 1.
J Virol. 1992 Dec;66(12):7517-21.
PMID: 1433527

Dirckx L, Lindemann D, Ette R, Manzoni C, Moritz D, Mous J.
Mutation of conserved N-glycosylation sites around the
CD4-binding site of human immunodeficiency virus type 1
GP120 affects viral infectivity.
Virus Res. 1990 Dec;18(1):9-20.
PMID: 2082620

Fisher AG, Collalti E, Ratner L, Gallo RC, Wong-Staal F.
A molecular clone of HTLV-III with biological activity.
Nature. 1985 Jul 18-24;316(6025):262-5.
PMID: 2410792

Popovic M, Sarngadharan MG, Read E, Gallo RC.
Detection, isolation, and continuous production of
cytopathic retroviruses (HTLV-III) from patients
with AIDS and pre-AIDS.
Science. 1984 May 4;224(4648):497-500.
PMID: 6200935

Ghrayeb J, Kato I, McKinney S, Huang JJ, Chanda PK,
Ho DD, Sarangadharan MG, Chang TW, Chang NT.
Human T-cell lymphotropic virus type III (HTLV-III)
core antigens: synthesis in Escherichia coli and
immunoreactivity with human sera.
DNA. 1986 Apr;5(2):93-9.
PMID: 3011373

Heidecker G, Lerche NW, Lowenstine LJ, Lackner AA, Osborn
KG, Gardner MB, Marx PA.
Induction of simian acquired immune deficiency syndrome
(SAIDS) with a molecular clone of a type D SAIDS retrovirus.
J Virol. 1987 Oct;61(10):3066-71.
PMID: 3041028

Fisher AG, Ratner L, Mitsuya H, Marselle LM, Harper ME,
Broder S, Gallo RC, Wong-Staal F.
Infectious mutants of HTLV-III with changes in the 3'
region and markedly reduced cytopathic effects.
Science. 1986 Aug 8;233(4764):655-9.
PMID: 3014663

Adachi A, Gendelman HE, Koenig S, Folks T, Willey R,
Rabson A, Martin MA.
Production of acquired immunodeficiency syndrome-associated
retrovirus in human and nonhuman cells transfected
with an infectious molecular clone.
J Virol. 1986 Aug;59(2):284-91.
PMID: 3016298

Sakai K, Dewhurst S, Ma XY, Volsky DJ.
Differences in cytopathogenicity and host cell range
among infectious molecular clones of human
immunodeficiency virus type 1 simultaneously
isolated from an individual.
J Virol. 1988 Nov;62(11):4078-85.
PMID: 3172338

Sakai K, Ma XY, Volsky DJ.
Low-cytopathic infectious clone of human immunodeficiency
virus type I (HIV-I).
FEBS Lett. 1988 Oct 10;238(2):257-61.
PMID: 2458968

More papers related to serological analysis of the products
of cloned HIV genes, etc.

Chandra A, Gerber T, Kaul S, Wolf C, Demirhan I, Chandra P.
Serological relationship between reverse transcriptases from
human T-cell lymphotropic viruses defined by monoclonal
antibodies. Evidence for two forms of reverse
transcriptases in the AIDS-associated virus, HTLV-III/LAV.
FEBS Lett. 1986 May 12;200(2):327-32.
PMID: 2423366

Chakrabarti LA, Ivanovic T, Cheng-Mayer C.
Properties of the surface envelope glycoprotein associated
with virulence of simian-human immunodeficiency virus
SHIV(SF33A) molecular clones.
J Virol. 2002 Feb;76(4):1588-99.
PMID: 11799153

Gorny MK, Williams C, Volsky B, Revesz K, Cohen S, Polonis
VR, Honnen WJ, Kayman SC, Krachmarov C, Pinter A,
Zolla-Pazner S.
Human monoclonal antibodies specific for conformation-
sensitive epitopes of V3 neutralize human
immunodeficiency virus type 1 primary isolates from
various clades.
J Virol. 2002 Sep;76(18):9035-45.
PMID: 12186887

Zhang PF, Bouma P, Park EJ, Margolick JB, Robinson JE,
Zolla-Pazner S, Flora MN, Quinnan GV Jr.
A variable region 3 (V3) mutation determines a global
neutralization phenotype and CD4-independent infectivity
of a human immunodeficiency virus type 1 envelope
associated with a broadly cross-reactive, primary virus-
neutralizing antibody response. J Virol. 2002 Jan;76(2):644-55.
PMID: 11752155

Ball JM, Payne SL, Issel CJ, Montelaro RC.
EIAV genomic organization: further characterization by
sequencing of purified glycoproteins and cDNA.
Virology. 1988 Aug;165(2):601-5.
PMID: 2841805

Rekosh D, Nygren A, Flodby P, Hammarskjold ML,
Wigzell H.
Coexpression of human immunodeficiency virus envelope
proteins and tat from a single simian virus 40 late
replacement vector.
Proc Natl Acad Sci U S A. 1988 Jan;85(2):334-8.
PMID: 2829181

etc...

Competing interests:   None declared


Re: Re: H2O toxicity 7 July 2003
Peter J Flegg,
Consultant Infectious Disease Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Re: Re: H2O toxicity

Any fool can sit at a computer keyboard and pull out hundreds of references to toxicity associated with HIV therapies. However, it is quite another matter to use one's experience to place the advantages and disadvantages of therapy into its proper clinical context.

Let me introduce both Chris Tyler and Carl Williams to a novel concept - that of risk-benefit analysis. For antiretroviral therapy, the balance of the equation is clearly and unambiguously weighted in favour of therapy (assuming it is prescribed according to the current national guidelines).

I am fully aware of the fact that the drugs have toxicities - that is undisputed. What is also undisputed is the fact that that since the widespread introduction of these "lethal" and "AIDS-causing" drugs in the West (a seven-fold sales increase between 1995 and 2000), both the death rate and progression rate to AIDS have plummeted. It is facts like these which contribute to the broad consensus and acceptance that HIV therapy is clearly beneficial.

I don't intend to get into a "point by point" rebuttal match over the references cited by Chris Tyler and Carl Tyler. Bitter experience (see the debate with David Rasnick http://bmj.com/cgi/content/full/326/7381/126/e#responses) tells us this leads nowhere fast. However I would like to highlight some misunderstandings that evidently still persist to this day, 15 years after the drugs were first licensed.

Firstly, zidovudine doses were up to three times higher in the late 1980s than are currently used now, and side effects (usually reversible on discontinuation or dose reduction) occurred at far higher frequencies than are seen today. Speculation 15 years ago about the scale of future toxicity is merely speculation, a fact true even then. Toxicities such as reversible/transfusion dependent anaemia affect only about 5% of recipients of current regimens. Sick people with AIDS get anaemia — but this is usually multifactorial and seldom due to zidovudine alone.

Secondly, pointing out that individuals who have died from AIDS are more likely to have had treatment with zidovudine than those who remain healthy is tantamount to saying patients who have died from cancer are more likely to have had chemotherapy than patients who are well enough not to require chemotherapy. Remember that HIV therapy is reserved for symptomatic patients (these are by definition more advanced, and therefore more likely to die).

I am called to task by Carl Williams, who thinks my death by drowning analogy is "frankly offensive". Yet he accepts uncritically Chris Tyler's descriptions of zidovudine as a drug "responsible for the agonizing death of many thousands", and one that "eats away the lining of the intestines". Can we see references for these studies please? Zidovudine is also apparently a "failed chemotherapy agent"(this is relevant how?) which was "approved on the basis of fraudulent human trials". Carl Williams is quick to cite a legal case brought by Anthony Brink against Glaxo-Smith-Kline; if HIV dissidents persist in claiming HIV trials were fraudulent they had better get hold of some good lawyers. (Oh, I believe Anthony Brink may be available since the collapse of his case against GSK).

Competing interests:   Attendance at drug company sponsored HIV conferences/meetings


If you can bear to hear the truth you've spoken Twisted by knaves to make a trap for fools 9 July 2003
Carl Williams,
Lay person
TQ11 0lQ

Send response to journal:
Re: If you can bear to hear the truth you've spoken Twisted by knaves to make a trap for fools

Peter Flegg's assurance that the experience of physicians (presumably those who attend drug company sponsored HIV conferences/meetings), through a risk-benefit analysis, ensures that individuals diagnosed HIV + can expect a 1 in 3 chance of avoiding clinical and laboratory adverse effects at any one time on HAART, will no doubt be of great comfort to those newly diagnosed.  

However I am not sure that the readers of the BMJ debate will view his comment: "Any fool can sit at a computer keyboard and pull out hundreds of references to toxicity associated with HIV therapies" particularly supportive of his notion that HIV therapy is clearly beneficial.  

Regardless of whether or not I am a fool, Peter Flegg's assertion that: "the balance of the equation is clearly and unambiguously weighted in favour of therapy", still remains un-supported by clinical research - as I pointed out in my original response to his 'drowning' analogy.  It is the absence of any supportive research that individuals are better off taking therapy than not, rather than the abundance of negative data associated with those who are taking therapy, that I have drawn attention to.  

I question the relevance of Peter Flegg's remarks: "It is facts like these which contribute to the broad consensus and acceptance that HIV therapy is clearly beneficial". In 1996 the consensus advocated: "hit hard hit early" and ever since that time the consensus has been shifting in favour of delaying the initiation of therapy for as long as possible, - hardly an indication that the therapy itself is responsible for the benefits Peter Flegg describes.  

During the era of AZT Monotherapy, the median time from HIV diagnosis to initiation of treatment was 2.1 years.  During the era of double therapy, this had been extended to 6 years and by the time triple, or combination therapy began, the median time had stretched to 7.7 years.  

I don't deny that it is entirely possible that currently available therapies are considerably less toxic than previous regimens.  However, as the few examples that I cited were from the past 2 years, one can only draw the conclusion that previous regimens must have had horrendous problems (a point that Chris Tyler has drawn attention to).  Regardless of the relative toxicity between HAART and previous therapies, it remains true that until such time as proper randomised, double- blinded placebo, controlled studies show that there is a benefit from receiving HAART as opposed to no therapy at all, it remains, as Peter Flegg has pointed out, merely "speculation".  

Regards
Carl Williams

Competing interests:   None declared


A further plea for references on HIV purification 9 July 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

Send response to journal:
Re: A further plea for references on HIV purification

A further plea for references on HIV purification

In our rapid response "A plea for the references on HIV purification" (3 July 2003), we asked "Could Brian Foley or anyone else please give us a few of the "thousands" of references where HIV-1 has been separated "from the vast majority of other material", in other words, purified? In the same rapid response we wrote: "…we implore with him to provide a few references that prove: (i) that the molecules used in "cloning of a complete viral [HIV] genome" originated from HIV particles; (ii) cloning of HIV; (iii) that the HIV "Genetic Sequences" in his databases originated from HIV particles." "We would be grateful to Brian Foley if he can provide us with references showing HIV-1 preparations in which "No apparent differences in physical appearance could be discerned among the viral particles in these regions" as Sinoussi et al. did and with "a high degree of homogeneity" and "virtual absence of DNA" as Crawford et al did."

In his rapid response "Re: A plea for the references on HIV purification", Brian Foley gave a long list of references. With one exception, all the references refer either to "HIV molecular cloning" or animal retrovirus molecular cloning. We have already repeatedly given reasons why molecular cloning is not proof for purification. In fact, molecular cloning of a viral genome cannot be achieved unless the virus is first purified.

The exception that Brian Foley gave is the 1984 paper by Gallo and his associates (1). In that paper, the only statement regarding purification is the following: "The yield of virus from H4/HTLV-III cells was assessed by purification of concentrated culture fluids through a sucrose density gradient and assays of particulate RT activity in each fraction collected from the gradient. As shown in Fig. 2b, the highest RT activity was found at a density of 1.16g/ml, which is similar to other retroviruses. The highest RT activity was found in the fractions with the largest amount of virus, as determined by electron microscopy". However: (i) Gallo did not published electron micrographs to prove HIV purification; (ii) According to Montagnier: "Gallo?..I don't know if he really purified. I don't believe so. I believe he launched very quickly into the molecular part, that's to say cloning". (2)

At present nobody including Brian Foley has come forward with proof of HIV purification. In the case of Montagnier's "purified HIV" there were not even particles present with the morphology of retroviruses. This means that to claim "HIV molecular cloning" is no different than to go into a veterinary surgery, take an unlabelled bottle of blood, clone the cellular DNA and claim molecular cloning of Dolly the sheep.

As Montagnier has stated, characterisation of viral proteins and the viral genome "demands mass production and purification. It is necessary to do that." (2) Unless Brian Foley finds proof for HIV purification then he like us will have to conclude that at present there is no proof for the existence of HIV proteins, the HIV genome and thus HIV.

References

(1) Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, Isolation, and continuos production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4; 224(4648):497-500.

(2) Tahi D. Did Luc Montagnier discover HIV? Text of video interview with Professor Luc Montagnier at the Pasteur Institute July 18th 1997. Continuum 1998 5:30-34.

Competing interests:   None declared


Re: A further plea for references on HIV purification 10 July 2003
Brian T Foley,
HIV Researcher
Los Alamos National Lab Los ALamos NM 87545 USA

Send response to journal:
Re: Re: A further plea for references on HIV purification

The Perth group states:
"In fact, molecular cloning of a viral genome cannot be achieved unless the virus is first purified. "

This is indeed NOT a "fact". A viral genome can indeed by cloned, sequenced and studied independent of any 100% pure preparation of viral particles. Thousands of viruses, including hundreds of retroviruses have in fact been cloned, sequenced and analyzed. No virus has ever been "purified" and analyzed by the exact methods that the Perth group claims are required. When asked to name one virus that has ever met their conditions, they listed two (the Bryan high titer strain of Rous sarcoma virus, and the Moloney Murine Sarcoma Virus) which are mixtures of two or mor viruses and thus have not been "purified and characterized" by the Perth group's criteria.

If it is indeed a "fact" that a virus must be purified before it can be cloned, then the dozens of infectious molecular clones of HIV-1 that have been cloned, sequenced and studied would be de facto evidence that HIV has indeed been purified.

The human immunodeficiency virus is a retrovirus of the lentivirus family or group of retroviruses. All retroviruses have two major life stages of the life cycle, the DNA provirus integrated into host cell DNA, and the viral particle containing two copies of an RNA genome. Most of the early infectious molecular clones of HIV-1 were created from the proviral DNA stage of the viral life cycle, and thus infected cells and not free viral particles were the source of the material. When Dolly the lamb was cloned, her genome was never "isolated" it was always mixed together with chromosomal proteins nuclear membrane proteins, and many other macromolecules as well as nucleotides and water and hundreds of other smaller molecules. The "proof" of her cloning cannot be made by any claims of 100% pure sheep DNA or anything like that. Anyone can make such claims. The proof needs to come from examining the DNA of the alledgely cloned sheep and showing that it is identical (or very very nearly identical) to the alledged parental clone. The Raelians have recently made news by claiming to have cloned a human. Are we to take their word for it that they "purified" a human genome or "isolated" a human nucleus conatining that genome? Or do we need evidence that the clone is genetically identical to the parent?

Isolation of 100% pure viral particles by centrifugation or any other method is NOT a necessary step in cloning a retrovirus or any other virus.

All lentiviruses look alike by the resolution of currently available electron microscopic methods. If someone were to obtain a 100% pure batch of viral particles we could not tell by looking at them if they were HIV or SIV or BIV, let alone exactly which subtype of the HIV-1 M group of viruses they belonged to. As with the case of the Perth group's examples of the Byan high titer strain of RSV and the Moloney murine sarcoma virus, the preparation of identical-looking particles could even be a mixture of several different viruses.

A molecular clone of a virus, whether it is a complete genome or only a fraction of one, can be sequenced to tell us exactly what virus the clone is derived from. An infectious molecular clone tells us not only what virus it is derived from, but also that the clone is viable and can produce progeny virions. In the case of human viruses it is not considered ethical to inject the progeny virions nor the cloned infectious DNA into a group of humans to prove that the clone produces disease in these medical "volunteers", so we can only test them in cell cultures to show that they produce similar pathologies in the cells (some strains of HIV-1 M group viruses induce syncytia in T-cell cultures, others do not, for example) and that the progeny virions have the properties of the parent (for example antibodies harvested from the infected patient from which the virus was derived, and from other patients infected with similar strains of HIV-1 M group virus bind to the progeny virus).

The sequences of the genomes (or fractions therof) of any organism from viruses to bacteria to mammals, can tell us not only about the organism the DNA was directly derived from, but also about the relationship of that parent to other organisms. If we look at a gorilla, a human and a chimapnzee for example we cannot tell if the human is more closely related to the chimpanzee or the gorilla. However if we sequence almost any small region (say 10 kilobases) of the genomes of the 3 organisms we can see that the chimpanzee and human DNA are a bit more similar to each other than the gorilla is to either the chimp or the human.

Likewise with viral DNA or cDNA sequences, we can tell the relationships of the viruses of the HIV-1 M group to each other, to the viruses of the HIV-1 O and N groups, and to the various SIVs that have been sequenced to date. These primate lentiviruses in turn can be compared to non-primate lentiviruses such as FIVs, BIVs, EIAVs, Visna and Jembrana disease virus. At some distance (which varies from gene to gene) it becomes impossible to dtermine the exact relationship between the organisms. For example, it is not exactly clear whether fungi are more closely related to vertebrates or to plants. Likewise it is not clear whether the primate lentiviruses are more closely related to one or another of the non-primate lentiviruses. It is not clear whether the common ancestor of lentiviruses is more likely to have lived in a primate or a nonprimate host.

If the Perth group thinks that there is some problem with the theory that HIV-1 and HIV-2 cause immune deficiency in humans, perhaps they should try to explain why the detection and sequencing of HIV-1 M group genomes in humans so very well correlates with the detection of immune deficiency diseases in only infected and not non-infected people. Not only does the pattern of epidemic spread of these viral genomes precisely coincide with the pattern of immune deficiency on a global scale (for example sequences of HIV-1 M group CRF01_AE virus appeared in Thailand coincident with the AIDS epidemic in Thailand) but it also coincides on local scales (for example the people infected with nef gene defective virus from transfusion in Australia survived longer than most people infected with viruses that have all genes functional). To just claim that they think that the chicken has to come before the egg instead of visa versa, does not explain why the whole barnyard is full of chickens and eggs with more eggs hatching into chickens every day.

Competing interests:   None declared


Risk/benefit of HIV therapy 10 July 2003
Peter J Flegg,
Physician
Blackpool, UK, FY3 8NR

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Re: Risk/benefit of HIV therapy

Once again the HIV dissidents and the HIV orthodoxy appear to be at an impasse regarding the risks and benefits of therapy. On the one hand, Carl Williams and Chris Tyler are apparently persuaded that the drugs are nothing but toxic poisons, with no merit or benefit whatsoever. This view is incorrect and unbalanced, but perhaps understandable in a world where the perception of risk can become so readily distorted that parents would rather their children face infections than be immunised, or will mutter into a mobile phone clamped to their ear about the unacceptable hazard from the mobile phone mast up the road, at the same time dragging on their umpteenth cigarette of the day.

The risk of harm from HIV therapy is real, but it is a risk well worth taking. We are not talking about some trivial complaint here, but a life-threatening and currently incurable illness. Since the late 1990s, the focus of therapy has shifted from using drugs that are as potent as possible to a strategy of using drugs that are as tolerable as possible while still remaining effective.

The dissidents' case is not advanced by confusing real with imaginary problems and describing them in lurid and emotive terms ("agonizing death of many thousands", "eating away the lining of the intestines", "fraudulent human trials"). Complete denial that therapy is associated with patients living longer, healthier lives does not help either. Carl Williams wishes to have references as to the efficacy of the drugs. I hope he takes the time to look at these studies and only then makes his mind up, rather than scouring the medical literature for the odd phrase that can be presented out of context as evidence to justify his predetermined convictions.

There are numerous clinical trials, and several meta-analyses of RCTs, which demonstrate the superiority of HIV therapy over no therapy (1-3). Carl Williams is living in cloud cuckoo land if he thinks it is ethical to conduct a RCT which is placebo-based on every newly available HIV drug. Drugs have to be tested against the most effective currently available therapy. But RCTs alone are not the only studies that show HIV therapy works, there is an abundance of data from large cohort studies, which provide a more realistic impression of how the drugs are used in clinical practice. These studies look at tens of thousands of patients and are remarkably consistent in demonstrating that the more drugs you take, the lower your risk of disease or death.(4-11). If you couple evidence like this with the evidence HIV physicians experience on a day to day basis in their clinics while treating patients and managing their side effects, the benefits of therapy are patently obvious.

Oh, and by the way, Carl Williams may indeed have cited recent papers about HIV drug toxicities (unlike Chris Tyler, who quotes only two references in 12 that were published in the last 5 years). In the first of these, the phrase "The indisputable benefits of therapy in patients with advanced disease are not so clear in asymptomatic patients with high CD4+ cell counts" appears and is actually cited by him. Well can I say now I agree with this entirely! His second reference quotes "In some patients, this [drug-related] morbidity could be worse than what one could expect from the progression of HIV-associated immune disease itself over the same period of time". Note the words "some" and "could" (not "most" and "will"). For his 3rd reference he quotes "more than two thirds of patients presented one or more clinical or laboratory adverse events which could have been due to antiretroviral treatment". Yes, adverse events can be frequent, but can also be minor, tolerable, self-limiting or even irrelevant (e.g. macrocytosis with zidovudine ). It is the lack of a suitable clinical context into which this statement is placed that makes me decry the "Google for -toxicity-" approach rather than a measured analysis of risk/benefit. This last quote came from the Swiss Cohort Study. Will Carl now accept the conclusions of the Swiss Study concerning efficacy of the drugs (11), or does he want to cherry-pick through articles until he encounters something that reinforces his confirmational bias?

References:

1. Staszewski S et al. Reductions in HIV-1 Disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials. AIDS 1997; 11:477-83.

2. HIV Trialists Collaborative Group. Zidovudine, didanosine and zalcitabine in the treatment of HIV infection: meta-analysis of the randomised evidence. Lancet 1999; 353: 2014-25

3. Jordan R et al. Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy. BMJ 2002; 324: 757-60.

4. McNaghten, A.D., et al. Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS Diagnosis. AIDS 1999 13:13, 1687-95.

5. Kaplan, J., et al. Epidemiology of Human Immuno-deficiency Virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clinical Infectious Diseases, 2000; 30 (Supplement 1), S5-14.

6. Mocroft, A., et al. Changing patterns of mortality across Europe in patients infected with HIV-1. The Lancet, 352: 1725-30, Nov. 28, 1998.

7. Mocroft, A., et al. AIDS across Europe, 1994-98: the EuroSIDA study. The Lancet, 356: 291-96, July 22, 2000.

8. Palella, F., et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine, 338:13, 853-60, 1998, March 26.

9. DeMartino, M. et al. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Journal of the American Medical Association, 284:190-7, July 12, 2000.

10. Dorrucci, Maria et al. Temporal changes in the rate of progression to death among Italians with known date of HIV seroconversion: Estimates of the population effect of treatment. Journal of Acquired Immune Deficiency Syndromes, 22:1, 65-70, Sept. 1, 1999.

11. Egger, M. et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: Prospective multicentre study. British Medical Journal, 315: 1194-9, Nov. 8, 1997.

Competing interests:   Attendance at meetings sposored by HIV drug companies


Re: Re: Distinguishing between true and "official" HIV infection 12 July 2003
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David, Causer, Helman Alfonso

Send response to journal:
HIV infection

It is the role of the doctor, not the patient, to interpret tests

Brian Foley quotes the Perth Group: "Do patients really play a role in interpreting their own tests?"

 He responds "And my answer is that of course they do in most cases, and they always should.  The patient always knows more about the patient's history than the doctor does.  An accurate diagnosis depends on more than test results, it also requires putting those results into the context of the whole picture…likewise for HIV antibody testing, the person being tested knows more about their history of sexual activities, IV drug use and needle sharing, and transfusions". 

There is no doubt the patient does know more about his medical history than his doctor.  The doctor's skill lies in obtaining that history and formulating it in such a manner he can decide whether or not a test is likely to assist arriving at a diagnosis.  On many occasions no test is warranted.  The greatest physician who ever lived, Sir William Osler, taught his students,  "Talk to the patient long enough and he will tell you what is wrong with him".  However, once a test is performed the patient plays no role in interpretation.  Not even if the patient is a doctor.  A visit to the coronary care unit of any hospital will not reveal patients sitting up in bed studying their chest X-rays or ECGs.

 Brian Foley appears to believe particular antibody test results (using criteria of his choosing), indicates HIV infection if the person being tested has a history of "sexual activities, IV drug use and needle sharing, and transfusions".  What Brian avoids is telling us how he interprets the same test result in a person who is not in a risk group and is healthy.

 If a positive test in a healthy, no risk person does not indicate HIV infection then how does Brian reconcile this with the advice from the CDC that "HIV testing consists of an initial screening with two types of tests commonly used to detect HIV infection. The most commonly used initial test is an enzyme immune assay (EIA) or the enzyme-linked immunosorbent assay (ELISA).  If EIA test results show a reaction, the test is repeated on the same blood sample. If the sample is repeatedly the same result or either duplicate test is reactive, the results are "confirmed" using a second test such as the Western blot.  This more specific (and more expensive) test can tell the difference between HIV antibodies and other antibodies that can react to the EIA and cause false positive results.  False positive EIA results are uncommon, but can occur.  A person is considered infected following a repeatedly reactive result from the EIA, confirmed by the Western blot test" (emphasis added).  http://www.hivtest.org/subindex.cfm?FuseAction=FAQ#2

The CDC assertion makes no mention of the patient's history, healthy or otherwise.  For the CDC, as for all HIV experts, the tests are considered virtually 100% specific rendering clinical data irrelevant.

At www.cdc.gov/mmwr/preview/mmwrhtml/mm4923a2.htm we read: In 1999 "Of the estimated 800,000--900,000 persons infected in the United States, approximately one third have yet to be diagnosed". At www.cdc.gov/mmwr/preview/mmwrhtml/mm5225a1.htm the CDC report: "In  2000, an estimated 850,000--950,000 persons in the United States were living with HIV, and approximately one fourth of these persons did not know they were infected (1)".

In reference 1 (www.cdc.gov/mmwr/preview/mmwrhtml/mm4923a2.htm), "During January 1997--September 1998, 615 persons with HIV infection diagnosed and reported met the criteria for the study; these persons represented 15% of all persons with HIV infection diagnosed and reported during this period from Alabama, New Jersey, and Tennessee.  Of the 543 persons determined eligible after follow-up by state health departments, 180 (33%) completed interviews, 127 (23%) refused to be interviewed, and 235 (43%) could not be located.  Among persons with known dates, 148 (86%) of 173 were interviewed within 12 months of the self-reported date they learned they were HIV-infected (median: 6 months)".

Twenty-three (28%) of 81 males and 69 (70%) of 99 females could not be classified as having recognised transmission risk or as having sexual contact with an HIV-infected partner or one with a documented transmission risk…Among 68 males stating a primary reason for being tested, the leading reasons were because a doctor or friend told them to be tested (28%) and because they were worried they might be infected even though they were not sick (22%).  Among 90 females stating a primary reason for testing, the leading reasons were because of pregnancy care (33%) and because a doctor or friend told them to be tested (18%)…Of 180 persons interviewed, 151 (84%) reported receiving medical care for HIV infection since diagnosis.  Among the 27 persons who responded that they had not received medical care for their HIV infection since diagnosis, 13 (48%) reported feeling well and not thinking it was important to seek medical care right away, and 12 (44%) reported not wanting to think about being HIV-positive as reasons for postponing seeking health care right away.

 Clearly, in this study there are a number of seropositive, healthy people devoid of risk factors.  (We could also argue "could not be classified…" is CDCspeak for "has not admitted risk factors to the study authors").  This raises a number of questions: 

  1. How should a physician interpret his healthy, no risk patient's positive antibody test?  Or, if we follow Brian's method, how should the patient interpret his own test?
  2. Although the criteria for a positive "confirmatory" Western blot are not stated they are likely to be those of the CDC, that is, two reactive bands chosen from p24, gp41 and gp120/160.  These would not "confirm" HIV infection in Australia and, depending on the exact band pattern, in other countries.  How should such tests be interpreted if a patient were to emigrate, for example, to Australia, where combinations of four bands are required?
  3. Does Brian Foley agree with the CDC that "A person is considered infected following a repeatedly reactive result from the EIA, confirmed by the Western blot test" regardless of the patient's history?
  4. For test manufacturers such as Abbott Laboratories [1], "Specificity [is] based on an assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in random donors".  If this is the case must not we also conclude that positive tests in all healthy persons, including those in the above CDC study, are false positives?  It is possible to imagine that some of the healthy, no risk persons in this study could have been "random donors".   If they are regarded as false positives by one group of evaluators how can they be regarded infected by another?  How would physicians, patients and their relatives react to this conundrum?  Would Brian Foley recommend antiretrovirals to such individuals?  Or their unborn children?
  5. In regard to point 4, since the  vast majority of seropositive individuals are clinically healthy, how can we avoid concluding "the global burden of HIV" is a gross misapprehension?
  6. If the American Red Cross, the CDC, the Association of State and Territorial Public Health Laboratory Directors, the FDA, The Consortium for Retrovirus Serology Standardization, the HIV experts and biotechnology companies cannot agree on a definition of a positive "confirmatory" Western blot, what hope do physicians or their patients have for interpreting these tests?

Brian also doubts that in the MultiCenter AIDS Cohort Studies a single "strong"  Western blot band was considered "proof" of HIV infection.  He also states "A single band may have been all that was required for enrollment in the study, but scientists rarely speak of "proof" of anything".

  1. The 4954 men enrolled in the MACS were enrolled beginning in early 1984, that is, before the antibody tests were developed and long before they were introduced into routine, clinical practice.
  2. In "determining antibody to HIV…All specimens for which ELISA results suggested seroconversion, (ie increase from <0.5 to 0.5 were examined by immunoblot techniques.  A score of 0 was assigned for a negative band, 1 for a weakly reactive band, 2 for a moderately reactive band, and 3 for a strongly reactive band to p15, p24, p31, p45, p53, p55, p64 or p120.  The scores of all bands were summed and a value 3 was defined as positive, 2 as equivocal and £ 1 as negative.  [Even this has changed.  Nowadays one band is considered indeterminate].  The validity of this method has been evaluated by prospective assessment in this cohort".  Thus (i) one "strong" band was considered a positive Western blot;  (ii) these data again show that the gold standard for the antibody tests was clinical data and not HIV itself [2].
  3. Since the band criteria for a positive WB have changed over time, including in the MACS, it is possible there are a number of gay men, alive or dead, who nowadays would not be considered HIV infected based on their earlier tests.   If they are sick or dead, why?
  4. Scientists may or may not "rarely speak of proof" but do the CDC criteria of a twice reactive ELISA/single positive WB prove HIV infection or not?

Lastly, Brian would like to know how many men in the MACS had one "strong" band.  So would the Perth Group, especially given (3).  Unfortunately, the individual Western blot patterns are not published.  Brian's "understanding" is that "almost all HIV-infected people produce strong immunological responses to many HIV proteins during the course of their infection, and almost none (perhaps less than 2%?) produce an immunoglobulin response to only one of the HIV-1 proteins".  Brian may be right but upon what data is his "understanding" based?  The fact is that once a laboratory or institution or country sets its criteria for a positive Western blot then any patterns not fulfilling these criteria are either negative or indeterminate.  According to HIV expert Anthony Fauci, "There are two possible explanations for an indeterminate western blot result.  The most likely explanation is that the patient has antibodies that cross react with one of the proteins of HIV…the least likely explanation…is that the individual is infected with HIV" (Harrison's Principles of Internal Medicine, 13th edition, page 1584).  It is also an inescapable fact that the positive criteria under one laboratory, institution or country may be indeterminate under another.  In this regard, Brian's explanations about changing band patterns during the early days of an individuals' infection or percentages of seropositives who do not have "strong immunological responses" are irrelevant.  If Brian believes that sooner or later all WB band patterns "evolve" into a particular pattern he asserts diagnostic of HIV infection, (a) what pattern is it?  (b) what is his proof; (c) why isn't this pattern universal?

Would anyone entertain the ECG criteria for an acute myocardial infarction differing between countries?  Or the radiological criteria for an acute, traumatic dissection of the