Royal Perth Hospital, Western Australia,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Andrew Maniotis, Christian Fiala
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More Requests to Peter Flegg
In his rapid response "The Perth Group reasoning", 2 March, Peter Flegg wrote: "However, as incredible as this statement appears, things get even worse, for neither of the studies referred to support what the Perth Group claim they do. Dissidents have consistently misrepresented these studies over a number of years and distorted their findings to fit their preconceptions".
There is no need to misrepresent and distort the Padian and the Gray studies to conclude that at present there is no proof for heterosexual transmission of "HIV". The data speak for themselves. (See table and http://bmj.com/cgi/content/full/324/7344/1034#resp3)
Numbers of years to attain 50% and 95% probability of
transmission of "HIV" in United States and Uganda assuming sexual contact
once every three days
Numbers of years to attain 50% and 95% probability of transmission of "HIV" in United States and Uganda assuming sexual contact once every three days
Note: The Gray paper did not fulfil all the criteria for a prospective study and the Padian is the cross-sectional part. In the prospective there was zero transmission.
Discussing the Gray et al study, Peter Flegg wrote: "So part of their study proposal was to determine if differing subtypes of HIV had differing infectivity. They state: "since the transmission probabilities per act of sexual intercourse in these populations are similar, the generalised HIV-1 epidemic in Uganda is unlikely to be caused by a greater infectivity of subtypes A and D" and conclude: "…greater infectivity of predominant HIV-1 viral subtypes is unlikely to account for the explosive HIV-1 epidemic in sub-Saharan Africa. This statement does not mean what many dissidents imply (i.e. that sexually-transmitted HIV cannot account for the "AIDS" epidemic), but merely that subtype variability does not account for the explosive nature of the epidemic in Uganda. Indeed, the Rakai Project authors give clues as to what is really relevant, since their "headline" conclusion was that "Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population"."
Gray et al determined the probability of "HIV-1" transmission per coital act irrespective as to what were "the main determinants of HIV-1 transmission, the "HIV-1" subtypes, the "Higher viral load and genital ulceration", or any other factor. The "HIV-1" transmission per coital act reported by Gray et al included all the determinants of "HIV-1" transmission.
Peter Flegg wrote: "The second paper to be misconstrued by the Perth Group is the "Padian Study" (4), so beloved by dissidents over the years because it found a low transmission rate of HIV in heterosexual couples (hardly surprising, because the couples had already demonstrated a low likelihood of transmission prior to study entry, they all entered the study well after the highest risk transmission period for HIV (which is around seroconversion), they were all advised on safe sex precautions during the study and widely used barrier techniques). The Perth Group actually refer to only one part of Padian's study (naturally enough the part that can be most easily reinterpreted as corroborating their claim)".
The Padian study did not find "a low transmission rate", but zero transmission rate. The "low transmission rate" was found in the cross-sectional part of the study, which Padian herself considers not as reliable as the prospective part. Even in the cross-sectional, after 10 years with no effort and money spared, she could report only 2 cases of female-to-male transmission. According to Padian both of these cases were questionable.
Nowhere in the Padian study is there evidence that the couples "had already demonstrated a low likelihood of transmission prior to study entry”. There is no evidence that "they all entered the study well after the highest risk transmission period for "HIV” or that the highest risk of transmission is around seroconversion. There was intensive safe sex education, but even so, 25% of the couples were not practising safe sex at the end of the study.
It is true that many times we refer to only one part of the Padian study. It is also true that that part is the cross-sectional which is the less reliable and where a "low transmission rate" has been found and not the prospective study where the transmission rate was zero.
Peter Flegg wrote: "Again, I would prefer to accept Padian's interpretation of what her own studies show, rather than what the Perth Group thinks they show. Professor Padian has even had to publicly refute some of the dissident claims concerning her studies (5)".
We have no access to the San Francisco Chronicle. As far as we are concerned, the Padian evidence speaks for itself.
Peter Flegg wrote: "These papers, like those of the Rakai Project, do not support any possible interpretation that HIV is not sexually transmitted. To use them as "proof" of such merely demonstrates how shallow is the science base upon which the PG relies for their "evidence"."
The per contact transmission rates reported in the Padian and Rakai studies mean that, on average, several years to many decades must pass and hundreds to thousands of sexual contacts must occur in order for HIV transmission to ensue (see above table and www.theperthgroup.com/OTHER/livio.html). Does Peter Flegg regard these data from these two particular studies proof of transmission of "HIV" and consistent with, for example, “the explosive nature of the epidemic in Uganda”? If so, upon what basis? If not, surely after more than 20 years of sexual transmission of the deadliest virus, "HIV", there must be hundreds, if not thousands of other studies Peter Flegg can cite which prove sexual transmission. We would be grateful if he could point us to just a few of these studies.
In our rapid response, "Perth Group response to Peter Flegg", 24 February, we wrote: "In one of our rapid responses to Peter Flegg, "Yes. It is about time to move on" (May 5th 2003), we asked him to give us a reference which proves heterosexual transmission of "HIV". We drew his attention to the fact that for such a study to be accepted as scientific proof for heterosexual transmission it must satisfy the following: "Be prospective. Use tests which have been proven to be specific. Have a statistically meaningful population. The result must be statistically significant and must exclude other possible routes of infection". Peter Flegg does not need to spend too much of his time in giving us more than one such reference. Any physician who treats patients on the basis that they had acquired the condition sexually should have such references at his fingertips. Yet so far he has not even given us one reference. Why?"
We are still waiting.
In his rapid response, "Misinformation on HIV and its consequences", 2 March Peter Flegg wrote: "I have been asked by the Perth Group to provide evidence that dissident misinformation has led to my patients becoming infected with HIV".
We did not ask Peter Flegg to "provide evidence that dissident misinformation had led to "his patients becoming infected with HIV". We can speak only for ourselves. That is why our request was specific: Would Peter Flegg also please give us the misinformation which we, the Perth Group, has published, which leads to his patients being infected or infecting others?
Peter Flegg wrote: "It is true that some dissidents like the Perth Group have sufficient nous to never be seen to directly encourage such behaviour, but there are wider implications to their stance on HIV/AIDS and its treatment. If we turn back to the original subject of this debate, namely South Africa, it is worth remembering that Thabo Mbeki's disastrous ideas about AIDS derived in part from information gleaned from an HIV dissident internet site (Virusmyth). He and his government have subsequently adopted a stance that has heavily relied on dissident support for its action, both through direct consultation and through their input into the Presidential "AIDS Panel". One particularly tawdry episode concerns the denial by the SA Government of nevirapine to its own citizens to prevent mother to child transmission of HIV. A significant role has been played by the Perth Group in convincing Mbeki of the "correctness" of this decision through the promotion of the wretched Perth Group document on Nevirapine (1). It has been estimated that as a result of the Government's inaction, over 40,000 infants have been infected annually in South Africa over the last few years".
To date there has been only one clinical trial of the use of nevirapine to prevent mother-to-child transmission, the HIV NET 012. It is true that we found many problems with the design, and execution of this study.
See www.theperthgroup.com/presentations.html and our monograph cited by Peter Flegg.
The FDA also noticed some problems. So, would Peter Flegg please give us the scientific reasons that made him call the "Perth Group document on Nevirapine", "wretched"?
(i) the senior author of the HIV NET 012 study, Brooks Jackson, "no researcher…can assess a drug's effectiveness with scientific certainty without testing it against a placebo. That's the only way we can know if a short course of AZT or nevirapine is better than nothing".1
The HIV NET 012 study had no placebo.
(ii) the FDA, "….Viramune is not FDA approved:
(1) for the prevention of HIV in mother-to-child transmission, by itself or in combination with other drugs. If used in this fashion, it would be an off-label use.
(2) Viramune is FDA approved for HIV infected, pediatric patients 2 years and above. It is not approved for use in the newborn at their time of birth to prevent whatever HIV is transmitted from the mother establishing itself as infection in the newborn."
Given the above facts, could Peter Flegg please advise what would be the scientific reasons for President Thabo Mbeki and his government to give nevirapine to South African pregnant women and their newborns?
One should acknowledge the indispensable contributions of clinicians such as Peter Flegg to the care of patients with AIDS. Notwithstanding, in case of a deadly virus, as HIV is said to be, the first step for a physician responsible for the care of such patients, is to be convinced that "Currently available HIV antibody tests are extraordinarily accurate".2 In this regard we would appreciate knowing whether Peter Flegg agrees that:
1. Patients are not necessarily infected with the antigens with which their antibodies react. For example, the serological diagnosis of infectious mononucleosis relies on the detection of antibodies that react with horse or sheep erythrocytes (the Monospot and Paul-Bunnel tests). Patients with Group A streptococcal infections or syphilis have antibodies that react with heart muscle proteins.3 4 Patients with measles develop antibodies that react with most of the antigens present in the HIV test kits.5 Patients with mycobacterial injections develop antibodies which react with the antigens present in the HIV test.6
2. Cross reactivities are largely responsible for such behaviour.7-9
3. Many researchers including Stratis Avrameas from the Pasteur Institute have proven that "antibodies are polyspecific, that is, they are able to react with various dissimilar antigens such as: proteins, nucleic acids and haptens" and "they are able to react with more than to self or non-self antigens, often without any apparent antigenic similarities".10
4. "Cross-reactive antibodies may have higher affinity with antigens other than the inducing antigen".11
5. AIDS patients are characterised by multiple, repeated and heterogeneous antigenic stimuli, and typically have hypergammaglobulinaemia.
6. Hypergammaglobulinaemia per se increases the probability of cross-reactions and in fact predicts a positive "HIV" antibody test.12
7. The potential for cross-reactivities precludes the introduction of a diagnostic antibody test into routine, clinical practice until the specificity of the reactions has been determined by the use of a gold standard.
Assuming the antigens in the "HIV" test kits are the proteins of a unique, exogenous retrovirus, what convinces Peter Flegg that the antibodies in his patients which react with these antigens are directed against and are specific to a retrovirus, "HIV"? Could they not predict the onset, course and outcome of the AIDS diseases even if they did not prove infection with a retrovirus?
In regard to "HIV" seropositive mothers, their infants and antibody specificity, we would be grateful for Peter Flegg's view on the following:
In 1987 the CDC advised: "Most of the [CDC] consultants believed that passively transferred maternal HIV antibody could sometimes persist for up to 15 months". 18 In 1991 the CDC extended the time to 18 months 13 and by 1995 "…the range of WB seroconversions might eventually extend beyond 30 months", 14 that is, at double the age "believed" eight years earlier. Before the AIDS era the evidence was that transplacental maternal antibody in offspring did not persist beyond nine months.15 In 1993, Parekh from the CDC developed "a human immunodeficiency virus type 1 (HIV-1)-specific 1gG-Fc capture enzyme immunoassay (1gG-CEIA) to elucidate the dynamics of HIV-1 maternal antibody decay and de novo synthesis of HIV-1 antibodies in infants". He and his colleagues demonstrated a rapid decay of maternal "HIV" antibody "with decline to background levels by 6 months".16 In other words, if the "HIV" antibody test is specific, any child who has a positive "HIV" antibody test beyond 9 months should remain positive for the remainder of his or her life. In the only study providing a detailed analysis of post partum loss of infant HIV seropositivity, the European Collaborative Study, 17 approximately 23% of the children became seronegative between birth and 9 months. However, 59% became seronegative between 9 and 22 months. Since the latter cannot be due to loss of maternal antibodies, the only explanation is that either: (i) the antibody test is non-specific or; (ii) the children managed to clear "HIV" infection without treatment. If 23% of children test positive because of maternal antibodies and in 59% the test is non-specific, how certain can Peter Flegg be that in the remaining 18% of children the test will not also serorevert after 22 months? Or if the test remains positive, is it a true positive? May we ask, what does Peter Flegg tell the mother of a child who tests positive between 9 and 30 months and what is his approach to the clinical management of this child?
May we also ask, does Peter Flegg inform his patients that the "HIV" antibody tests have not been verified against "HIV" itself, that is, against "HIV" isolation?
Peter Flegg wrote: "On their own web site (2), The Perth Group claim there is no proof for the statement that "HIV/AIDS is infectious, either by blood, blood products or sexual intercourse". They also claim "AIDS will not spread outside the original risk groups." In fact all of their claims are specious, and have been refuted to orthodox science's clear satisfaction. The continued promotion of their view that HIV/AIDS is not proven to be infectious, and cannot spread outside the "original" risk groups poses a great danger to those who, possibly in denial and uncertain and confused about their own diagnosis, might be readily seduced by the message that their own infection does not even exist or is not transmissible."
Would Peter Flegg please tell us, THE PERTH GROUP, where we have been "refuted to orthodox science's clear satisfaction."
1. Swingle AB. The pathologist who struck gold. Hopkins Medical News 2001;Spring/Summer 2001.http://www.hopkinsmedicine.org/hmn/S01/feature.html
2. Focus on the HIV-AIDS Connection, 2001. http://www.niaid.nih.gov/newsroom/focuson/hiv00/default.htm
3. Malkiel S, Liao L, Cunningham MW, Diamond B. T-Cell-dependent antibody response to the dominant epitope of streptococcal polysaccharide, N-acetyl-glucosamine, is cross-reactive with cardiac myosin. Infection and Immunity 2000;68:5803-8.
4. Walter JB, Israel MS. General Pathology. London: J & A Churchill, 1970.
5. Baskar PV, Collins GD, Dorsey-Cooper BA, Pyle RS, Nagel JE, Dwyer D, et al. Serum antibodies to HIV-1 are produced post-measles virus infection: evidence for cross-reactivity with HLA. Clin Exp Immunol 1998;111:251-6.
6. Kashala O, Marlink R, Ilunga M, Diese M, Gormus B, Xu K, et al. 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 1994;169:296-304.
7. Restani P, Beretta B, Fiocchi A, Ballabio C, Galli CL. Cross-reactivity between mammalian proteins. Annals of allergy asthma & immunology 2002;89 (6 Suppl 1):11-5.
8. Nossal GJV. Antibodies and Immunity. Harmondsworth, UK: Penguin Books Ltd, 1971.
9. Roitt IM. Roitt's Essential Immunology. Ninth ed. London: Blackwell Science, 1997.
10. Ternynck T, Avrameas S. Murine natural monoclonal antibodies: a study of their polyspecificities and their affinities. Immunol Rev 1986;94:99-112.
11. Berzofsky JA, Berkower IJ, Epstein SL. Antigen-Antibody Interactions and Monoclonal Antibodies. In: Paul WE, editor. Fundamental Immunology. 3rd ed. New York: Raven, 1993:421-465.
12. Brenner B, Schwartz S, Ben-Porath E, Tatarsky I, Varon D, Martinowitz U. The prevalence and interaction of human immunodeficiency virus and hepatitis B infections in Israeli hemophiliacs. Isr J Med Sci 1991;27:557-561.
13. CDC. 1994 Revised Classification System for Human Immunodeficiency Virus Infection in Children Less Than 13 Years of Age. Mortality and Morbidity Weekly Reports 1994;43 (RR-12):1-10.
14. Chantry CJ, Cooper ER, Pelton SI, Zorilla C, Hillyer GV, Diaz C. Seroreversion in human immunodeficiency virus-exposed but uninfected infants. Pediatr Infect Dis J 1995;14(5):382-7.
15. Stiehm ER. Immunologic diseases in infants and children. 3rd ed. Philadelphia: WB Saunders Company, 1973.
16. Parekh BS, Shaffer N, Coughlin R, Hung CH, Krasinski K, Abrams E, et al. Dynamics of maternal IgG antibody decay and HIV-specific antibody synthesis in infants born to seropositive mothers. The NYC Perinatal HIV Transmission Study Group. AIDS Res Hum Retroviruses 1993;9:907-12.
17. Epidemiology, clinical features, and prognostic factors of paediatric HIV infection. Italian Multicentre Study. Lancet 1988;ii:1043-6.
18. CDC. Current Trends Classification System for Human Immunodeficiency Viru (HIV) Infection in Children Under 13 Years of Age. Morb Mortal Wkly Rep 1987;36:225-30, 235-6.
Competing interests: None declared