Christopher S Tyler,
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Peter Flegg wrote: "Call a trial fraudulent when and only when you have evidence for a fraud having been committed (and not merely reciting a litany of trial violations and CRF errors "cut and pasted" from a dissident web site). To do otherwise is libel."
If claims are made about a drug, and the drug is approved during a trial based upon information that is faulty, incorrectly recorded, and in some cases made up; and when it is so known that the data is bad by investigators such that it is recommended to be thrown out, what else could it be called?
What is the purpose of having protocols for a drug trial if they are going to be widely ignored or violated?
What is the purpose of a control group, that is a placebo group, if the medications under investigation are being taken by both groups?
Under what conditions do falsely recording the length of time participants are in a trial lead to accurate information about the drug?
How can claims can be made about the toxicity profile of a drug when protocols are consistently violated, protocols which require accurate recording of adverse events?
It's apparent that Peter Flegg is not the least bit bothered by scientific sloppiness, as demonstrated by government documentation, which shows the AZT Phase II trials were flawed in such a way as to invalidate any claims made by that trial.
He may consider the information I presented as 'libel' and not 'fraud', but this is information taken from an FDA researcher's investigation of the trial, information which prompted a request that the data be thrown out because of the sheer number of problems and violations. Regardless of whether it was 'cut and pasted from a dissident website' or culled directly from the researchers documents (does it really matter where the text came from so long as the source is the same?), the information should be alarming to anyone whose interested in under what conditions drugs can be approved in the United States.
If this drug trial was legitimate, as I assume Mr. Flegg must feel it was (and is), why then were zidovudine doses "up to three times higher in the late 1980s than are currently used now"? Why did side effects occur "at far higher frequencies than are seen today" if the AZT Phase II trial data showed that the drug was so efficacious at those higher doses that the trial was prematurely ended so the placebo group could be given this miracle drug? Perhaps if the trial had been allowed to go to full term and the protocols were properly followed this information would have become more readily apparent sooner and not later.
In 1989, Dr. Anthony Fauci, then-director of the National Institutes of Allergy and Infectious Diseases (NIAID), cited an NIH study, known as Protocol 019, which 'clearly showed' that early administration of AZT would keep AIDS at bay in that population. Upon that study, he recommended that anyone with a positive antibody test (whatever the criteria were at the time) and less than 500 CD4 cells should start taking AZT at once. At that time, that meant 650,000 people in the U.S. The same Dr. Fauci, a decade later, said in an interview regarding the 'early treatment' of non-sick people, "We are adopting a significantly more conservative recommendation profile." (New York Times, Altman 2001).
However, after studying patients for another five years the lead researcher for Protocol 019, Paul Volberding, came to a new conclusion about AZT: "Zidovudine... does not significantly prolong either AIDS?free or overall survival." (1) Stated otherwise, hundreds of thousands of healthy people had taken AZT for five years for no "significant" reason, assuming that DNA chain termination is indeed "not significant."
I wonder if Mr. Flegg was eager to vilify people like Peter Duesberg in 1990 for opposing this type of 'early use' of AZT, which Mr. Flegg now insists is clearly in opposition to 'current strategy.'
It wasn't until a group of European researchers conducted a long, to full-term study that the worthlessness of AZT became apparent. The Concorde Trials (which wasn't funded by the manufacturer of AZT, unlike the Phase II Trials) showed that AZT conferred no benefit when given early, that is, to asymptomatic patients. In fact, as reported by the Coordinating Committee in the Lancet in April 1994: “A total of 172…participants died [169 while taking AZT, 3 while on placebo] …The results of Concorde do not encourage the early use of zidovudine in symptom-free HIV-infected adults.”
While Mr. Flegg assails dissidents for not being up on current treatment guidelines, he may wish to know that HIV/AIDS realists were urging that non-sick people stay away from being 'medicated' with DNA-chain terminators long before 'current play' policies were put in place. It was apparent to us that 'clear evidence' pointed to the fact that people on AZT did worse than those not taking it.
Peter Flegg wrote: "I will try to summarise the current state of play regarding HIV drugs in a single sentence: With respect to therapy with the presently available antiretroviral drugs, there is clear evidence that in asymptomatic HIV infection the balance of the risk/benefit equation is in favour of no treatment (or a deferral of treatment), while in symptomatic/advanced HIV infection the balance of the risk/benefit equation strongly favours treatment."
It is true that currently, after years of 'hit-hard, hit early' and AZT administration to healthy people, the general consensus is to wait treating a person until manifestations of illness occur. Current guidelines counsel a physician not to initiate 'therapy' until a CD4+ count of less than 350 has been reached. A person is considered to have 'full blown' AIDS when 200 is reached (regardless of their actual health status).
Although a hard lesson has been learned by many in the medical profession regarding the dangers of 'early intervention' with the cocktail, and although guidelines have become more conservative as a result, many people are still being treated with these drugs in ways that are NOW considered inappropriate.
Even though the authors of the website, hivmedicine.com, confirm the above basic treatment guidelines, they also state:
Many clinicians now prefer to start HAART at a later date. Disagreement has developed among many experts. Much of what is currently being debated, ranging from unrelentingly strict treatment to an exaggeratedly relaxed view on therapy, is based largely on subjective opinion, perhaps own experience, and often merely polemics. (2)
A post from a popular web portal for HIV antibody positive individuals provides a very recent examples (posted on the board this week).
Apparently this individual's physician isn't aware that the CDC guidelines forbid the use of PCR technologies for the diagnosis of individuals over the age of 18 months, and that the test kit says, "The AMPLICOR HIV-1 MONITOR Test, version 1.5 is not intended to be used as a screening test for blood or blood products for HIV or as a diagnostic test to confirm the presence of HIV infection". Nevertheless, even though the individual is still 'seroconverting', his doctor is recommending the use of these powerful drugs.
Another post from this week.
Not only does this person's normal CD4 count not deter the physician from putting this individual on anti-HIV medications, but diagnosing him by ELISA tests is simply dumbfounding. Apparently the doctor is under the impression that reactive ELISA's are both specific and reactive for one reason and one reason alone. Two, three, or ten consecutively reactive ELISA's don't tell you anything about the antibodies reacting in the test kit.
And again from this week, yet another post shows the cavalier nature some doctors seem to continue prescribing these drugs.
Even for people with illness it can be tempting for medical professional to use the catch all of HIV infection and thus treat them with non-specific HIV drugs like the nucleoside analogs and protease inhibitors. A really good example happened to a friend recently. At the end of last year, he started to become sick with flu like symptoms which persisted and became worse. He states in a personal correspondence with me;
But he resisted and he was treated for what was actually making him sick, the mycobacterium. He is one of the very few aware of the fact that antibodies directed against these mycobacterium can readily react with antigens in the non-specific HIV antibody tests, a point he brought up with his doctor only to be dismissed out-of-hand.
It's entirely possible that had he been put on the HAART, the non-specific, antibiotic like effect they can have on opportunistic infections would have wiped out the mycobacterium. It's also possible he would have begun suffering from the common problems associated with these drugs. However, once he recovered he would have been expected to stay on the cocktail, lest the virus 'mutate'. Like so many people he would now have to contend with the nagging side-effects of these drugs.
Peter Flegg wrote: "Don’t try to imply that zidovudine is more toxic than it is..."
In an October, 1997, letter to Nature Medicine (3:1052) Abraham Karpas of Cambridge University's Hematology Department, Stephen Ash of London's Ealing Hospital, and Douglas Bainbridge of the Royal London Hospital responded to what they called a "medico-political commentary" by Richard Wurtman of MIT's Department of Brain and Cognitive Sciences.
Further, In 1988 in the Lancet, Dournon et al had published a study of AZT, conducted at the Claude Bernard Hospital in France. They state:
As I've indicated in previous posts, there now exists plenty of data showing that AZT is not triphosphorylated by cellular enzymes into its active metabolite, AZTTP, and thus can't possible have an antiretroviral effect.(3) The question again arises, if AZT wasn't able to 'eliminate antigenemia' at the higher 1988 doses, but had significant toxicities, how can it possibly have a beneficial antiretroviral effect at doses used in 'current strategies'? Even if it were shown that AZT had no toxicities (which it clearly doesn't), it neither has any antiviral properties. In more direct terms, it's all risk and no benefit.
Mr. Flegg continues, "...because a supply of azidothymidine from Sigma Chemicals in the late 1980s, intended for non-medical laboratory use, comes in a bottle with a skull and cross-bones on the side. (this tale is a regular dissident attempt to mislead the unwary). For example, another chemical also comes with a similar toxic label, complete with skull and cross bones, accompanied by the following advice: Toxic if swallowed. After contact with skin, wash immediately with plenty of water. In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible). The chemical in question: Acetylsalicylic acid (aspirin)."
The difference between aspirin and AZT is that the warning for AZT states: "Target: Blood, Bone Marrow". This should be an ominous warning to people whose immune systems may either be compromised or who fear their immune systems may become compromised.
A warning similar to that of the non-medical use AZT on a bottle of aspirin only strengthens my point. Why aren't similar warnings put on AZT for medical use, especially for pregnant women who are counseled to stay away from substances like alcohol and aspirin? Shouldn't pregnant women be told AZT is a known teratogen and mutagen in order for them to make a fully informed decision? A bottle of Aspirin also contains the warning: "It is specially important not to take aspirin during the last 3 months of pregnancy as it may cause harm to the unborn baby and cause complications during delivery." Is aspirin more dangerous than a chemotherapy agent designed to terminates DNA synthesis indiscriminately?
It may be of interest to note that AZT is classified as a Class C drug by the FDA. There are five categories that the FDA uses for pregnancy drug classification, listed from the safest to most dangerous -- A, B, C, D, and X. AZT is listed in Category C and is described as a drug in which "safety in human pregnancies has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus."
Fever, pneumonia, anemia, and mitochondrial dysfunction appear in human babies said to be negative for HIV who were treated with AZT. (4)
Animals treated with AZT (mice, rats, dogs, monkeys) develop lymphopenia, weight loss, leukemia, T-cell depletion, thymic atrophy, anemia, neutropenia, thrombocytopenia, bone marrow depletion, muscle atrophy, hepatoxicity and more. (5)
Perhaps Peter Flegg can tell us why there was a sudden 10-fold increase in the mortality of HIV-antibody positive hemophiliacs right after the introduction of AZT. (6). Although the authors of the referenced study try and pin the blame on HIV by saying this dramatic increase was limited to HIV positive hemophiliacs, they failed to explain that those who tested negative on the antibody test would not have been administered AZT. Moreover, the mortality of hemophiliacs was steadily decreasing since the 1970s until 1987 when AZT 'therapy' was introduced. The AZT-mortality hypothesis also explains why the sudden upward shift in hemophilia mortality was independent of the severity of the hemophilia as Darby et al observed.
Peter Flegg wrote: "At the Barcelona AIDS conference in 2002 a University of Pittsburg researcher, Amy Justice, described the liver abnormalities within 2 North American cohort studies, concluding that that liver failure had become one of the most common cause of death in HIV-infected patients. Dissidents worldwide have inferred incorrectly that antiretrovirals have been responsible for this phenomenon, and have persisted in claiming this, despite being corrected on many occasions."
"Also conveniently ignored by the dissidents is that the majority of liver deaths have nothing to do with HAART whatsoever. "
This is not my conclusion, but that of orthodox AIDS specialists. In an interview with Dr. Justice, Jason Nusbaum says:
Dr. Justice laughed. "I think they are, yes. It's the dark side of these drugs."
Dr. Jon Kaiser, in an e-mail newsletter said:
Perhaps Peter Flegg should take up his concerns about misrepresentation of the data with this mainstream AIDS doctor and researcher.
Peter Flegg wrote: "The commonest reasons for cases of end stage liver disease and hepatocellular carcinoma have been hepatitis C or B co-infections. In the presence of HIV, HCV progression to cirrhosis is more rapid. Alcohol is also implicated as a major factor."
Hernandes et al, in research entitled "Antiretroviral hepatotoxicity in human immunodeficiency virus-infected patients" wrote:
In addition, they wrote;
It seems clear to these researchers what is causing the liver problems.
Macias J et al in research entitled, "Mortality due to liver failure and impact on survival of hepatitis virus infection in HIV-infected patients receiving potent antiretroviral therapy." wrote:
Finally, the quoted statement above only strengthens the dissidents' position that substance abuse of many types contributes greatly to the develop of so-called AIDS.
Beyond the discussion of liver toxicity of anti-HIV drugs, the claim is constantly made that the declining mortality is due to these drugs. This again needs to be addressed. As pointed out in earlier posts, people who aren't sick are going to live longer than people are are. The 1993 CDC AIDS definition suddenly lumped in a large number of non-sick "AIDS" patients. Non-sick people are going to have better outcomes/survivability than those who were considered AIDS patients only when they were sick. In addition, the claim is made that dramatic declines in mortality are the end result of medicating people with HAART. However, the decline began several years before HAART was introduced into clinical practice.
In fact, there would most likely have been even fewer deaths prior to the introduction of HAART had AZT not been prescribed to people since 1987. In a recent paper by Peter Duesberg, Claus Koehnlein, and David Rasnick, the authors write:
In addition, in the absence of untreated control groups it's impossible to tell the actual impact these drugs are having. True placebo controls have been abandoned in the era of anti-HIV drugs. As Christine Maggiore has said, "if they were only to access the thousands and thousands of people worldwide like myself who are positive, healthy and not taking any medications, they could use us as a historical control with regard to testing what are the effects of the AIDS drugs and what are we assuming are the effects of HIV." Christine Maggiore, founder of Alive and Well Alternative AIDS Organization, was 'diagnosed' HIV positive in 1992. Now, in 2004 she is still perfectly healthy without anti-HIV drugs and has two healthy children and a healthy husband.
Unfortunately we live in a time when people live in horrible fear of so-called AIDS. People who are supposedly infected with this retrovirus live in fear of getting their viral load and CD4 counts. People live in fear of receiving a diagnosis of being HIV positive.
One woman on the popular mainstream HIV/AIDS web portal AIDSMEDS.com writes;
Had individual gained access to the full range of information regarding the HIV antibody tests, she could have been saved grief by realizing that pregnancy can be one of many conditions which can cause the tests to become reactive.
Another individual writes:
Another man write:
And finally, another man wrote this week on an alternative HIV/AIDS board:
I could continue reciting more people's experiences but I believe these ones suffice.
1. P. A. Volberding, S. W. Lagakos, J. M. Grimes, D. S. Stein, J. Rooney, T.?C. Meng, M. A. Fischl, A. C. Collier, J. P. Phair M. S. Hirsch, W. D. Hardy, H. H. Balfour, R. C. Reichman, and the AIDS Clinical Trials Group, "A Comparison of Immediate with Deferred Zidovudine Therapy for Asymptomatic HIV?Infected Adults with CD4 Cell Counts of 500 or More per Cubic Millimeter," New England Journal of Medicine, 333 (1995): 401?407
Eleni Papadopulos-Eleopulos, Valendar F. Turner, John
M. Papadimitriou, David Causer, Helman Alphonso and Todd Miller, A
Critical Analysis of the Pharmacology of AZT and its Use in AIDS,
Current Medical Research and Opinion, Vol. 15: Supplement, 1999
4. Blanche et al 1999, Heresi et al 1997
5. Ayera 1998; Cronkite and Bullis 1990; Thompson et al 1991; McKallip et al 1995; Omar et al 1996; Grossman et al 1997; Inoue et al 1997; Gershenson et al 2000)
6. DARBY SC, EWART DW, GIANGRANDE LF, et al. Mortality Before & After HIV Infection in Complete UK Population of Haemophiliacs (letter). Nature (London) 1995; 377:79-82
Competing interests: None declared