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Alberta Reappraising AIDS Society |
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| David Crowe, President Phone: +1-403-289-6609 Fax: +1-403-289-6658 Email: David.Crowe@aras.ab.ca Kathleen Newell, Treasurer |
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6 Canada |
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| Rethinkers | Quotes | AZT | HAART | HIV Tests | Transmission | Library |
This article is copyright by John Lauritsen. He has given permission to print out this document and to photocopy it. It may not be published commercially without his permission (john_lauritsen@post.harvard.edu). Although this article is several years old, the questions it asks have never been answered, and consequently is still of great importance.
It is urgently necessary to review the toxicity of AZT in light of recent marketing developments. Prior to last August, AZT therapy was officially indicated only for “AIDS”or “ARC”patients who either had “a history of cytologically confirmed Pneumocystis carinii pneumonia (PCP) or an absolute CD4 (T4 helper/inducer) lymphocyte count of less than 200/mm3 in the peripheral blood before therapy is begun.” (Physician's Desk Reference) This changed dramatically in August, when a series of press releases were issued by the National Institute of Allergy and Infectious Diseases (NIAID) and other branches of the Public Health Service (PHS), claiming that AZT was beneficial for “HIV-infected”persons with “mild symptoms of immune system damage”and also for “HIV- infected persons who have not yet developed symptoms.”
The old rationale for prescribing AZT was that people with AIDS (PWAs) were suffering from a disease that was invariably fatal, that such persons had only a few months to live, and that AZT might extend their lives for a few more months. The idea was that in a desperate situation, drastic measures were called for. I have repeatedly argued that this viewpoint is wrong – that “AIDS”is not invariably fatal; that some PWAs have survived for many years and appear to be recovering; and that the only chance for recovery lies in strengthening the body, rather than injuring it through toxic chemotherapy like AZT.
Now a completely different game plan is in operation. With well-orchestrated propaganda emanating from NIAID, Gay Men's Health Crisis (GMHC), Project Inform, and various and sundry other “AIDS”groups, clinical researchers, and other confederates of Burroughs Wellcome (the manufacturer of AZT), physicians are now being urged to prescribe AZT for perfectly healthy people. The targeted individuals – estimated to be several hundreds of thousands in the United States alone – merely have antibodies to HIV-1, a retrovirus that has not yet been proven to be harmful, let alone the cause of the devastating AID Syndrome. Healthy people, who ought to look forward to living for several more decades, are now being conned into taking the most toxic substance ever prescribed for long-term use. Since gay men are the primary targets of AZT marketing, since AZT therapy would probably cause even an athlete in his prime to die within a few years, and since the alleged “benefits”of AZT rest upon fraud, it is not unreasonable to use the word “genocide”to describe what is happening.
In my articles in the Native I have analyzed the studies that allegedly demonstrate AZT's effectiveness, and have concluded that there is no scientifically credible evidence that AZT has benefits of any kind. Documents that the Food and Drug Administration (FDA) was forced to release under the Freedom of Information Act revealed that the Phase II (“double-blind, placebo-controlled”) AZT trials were worthless. The researchers covered up the fact that the study had become unblinded (thus violating the basic test design). Protocol violations were overlooked. Worst of all, the researchers deliberately used data that they knew were false. These fraudulent trials were the basis of government approval of the drug. [note 1]
Another study often cited as proof of AZT's benefits concerns patients who received AZT after the Phase II trials were prematurely terminated. [note 2] I have written an extensive analysis of this study, which is a rotten mixture of incompetence and dishonesty. [note 3] Through colossal incompetence the researchers lost track of 1120 patients, not knowing if they were even alive or dead. They then used statistical projection methods to guess what results they would have obtained if they had not lost the 1120 patients, presented their guesses as actual survival statistics, and made a number of grossly invalid comparisons in order to claim that AZT had extended lives. This “research”is a blatant exercise in disinformation, proving nothing except how farcical are the “peer review”standards of medical journals.
As appalling as these two studies were, they at least presented data, however dubious. The two studies that received so much fanfare last August didn't even go that far. The general public, physicians, PWAs, and health care workers were expected to accept “findings”which consisted of generalizations that were not even backed up by numbers. Normally a press release on a study is issued a few days before the publication of a report in a peer- reviewed medical journal. This is ethically obligatory, because physicians with the responsibility of prescribing a drug – especially one as toxic as AZT – are entitled to have recourse to hard data, a proper description of methodology, and an intelligent analysis of the findings.
On 17 August 1989 The U.S. Department of Health and Human Services (HHS) issued a press release, which began:
The alleged findings of the study (known as ACTG Protocol 019) were described in a vague paragraph, which did not give a single hard statistic. (See Box A following this article.)
Then on 24 August 1989 NIAID issued its own press release, “Results of Controlled Clinical Trials of Zidovudine in Early HIV Infection”. This two-pager covered both Protocol 019 (healthy persons) and Protocol 016 (persons with “mild symptoms”), and gave even less information than the HHS statement had. It made the preposterous assertion that “zidovudine toxicity experienced by the persons studied in Protocol 019 was minimal.”
I spent several days calling NIAID and various other PHS branches in an attempt to obtain some hard information about Protocol 019. They sent me a three-page “Backgrounder”entitled, “ACTG 019 - Questions and Answers”. This Q & A described the “results”of the study in one paragraph. (See Box B following this article.) As the reader can see, the statement in Box B is gibberish, it gives no real data, and it is in contradiction with the earlier HHS press release (Box A).
When I talked to the NIAID press officer who was supposed to be most knowledgeable about Protocol 019, and asked him some specific questions (which he was unable to answer), he told me frankly that I had all of the information he himself had – that there was nothing he could tell me I didn't already know.
Based on my knowledge of Protocol 019, equal apparently to that of anyone in the country, I constructed Table 1, which shows the findings in the simplest and most straightforward way possible. This table should be studied carefully by anyone (whether as patient, physician, or concerned party) who is considering the use of AZT for an “asymptomatic HIV-infected person”. Table 1 contains all of the data we have about Protocol 019.
The ordinary mind often fails to make the distinction between things as they are and things as they ought to be. For example, if the FDA is to do its job and protect the American public from dangerous drugs, it ought to have a system for keeping track of adverse reactions to a drug after it has been put on the market. Many people therefore assume that there is such a system. There is not. In this regard the United States takes an approach to drug regulation that is different from that of most other industrialized countries.
In the United States, all of the efforts in screening a new drug for adverse side effects are supposed to take place before the drug is approved. Once a drug has been approved – whether by hook, crook, or the intrinsic merits of the product – it's clear sailing from then on. In theory, physicians are supposed to report adverse effects to manufacturers, who are supposed to relay the information to the FDA. But in practice, with no incentives for compliance, no punishments for noncompliance, and with no federal data gathering system, the post-marketing surveillance is haphazard at best.
In contrast, Britain has a sophisticated and rigorously enforced system of post-marketing surveillance. The philosophy there is that some adverse effects of a drug only become apparent after a certain period of time – this is known as chronic toxicity – and that some adverse effects might be relatively rare, found perhaps in only 1 in 1000, or 1 in 5000 persons. Neither the chronic toxicity nor the rare adverse effects would likely be identified in pre-marketing trials, which typically involve only a few hundred subjects treated for a relatively short time.
Most new drugs take 9 to 10 years to go through the FDA's approval process, which includes initial safety tests in animals and human beings, clinical trials for efficacy and safety, and extensive review and analysis of the data. AZT, however, was rushed through the approval process faster than any drug in the FDA's history – less than two years. As a result, the officially recognized toxicities of AZT are far from complete. Further, the “non-official”toxicities of AZT, well known through the formidable PWA grapevine, are not being systematically recorded.
On top of all these problems, AZT was approved on the basis of research that was not just inadequate, but fraudulent. It is important to realize that the FDA has been for many decades a notoriously corrupt agency. Time and again officials in the FDA have colluded with drug manufacturers in order to suppress information about a drug's side effects. Recently Dr. Sidney M. Wolfe, director of the non-profit Public Citizen Health Research Group (HRG), charged that under Commissioner Frank E. Young, the FDA “is implicitly inviting all of the industries it regulates to join in the lawlessness.”[note 4] I am preparing a future article that will review some of the well-documented crimes against public health that have been committed through collusion of drug manufacturers, the FDA and other branches of the PHS, clinical researchers, and the American Medical Association.
Among the documents which the FDA was forced to release under the Freedom of Information ACT was the “Review & Evaluation of Pharmacology & Toxicology Data”for the drug Retrovir (generic name: zidovudine, aka AZT or azidothymidine), written by FDA toxicology analyst Harvey I. Chernov, Ph.D., and submitted in its final form on 29 December 1986. [note 5]
Chernov reviewed several dozen studies that had been completed, including in vitro studies and experiments on rats, mice, rabbits, beagle dogs, and human beings. Many additional studies had not been completed or had been planned but not begun. The single most important finding was that AZT was toxic to the bone marrow, causing anemia. Chernov wrote:
Chernov noted that AZT “was found weakly mutagenic in vitro in the mouse lymphoma cell system. Dose-related chromosome damage was observed in an in vitro cytogenetic assay using human lymphocytes.”
Evidence from the “Cell Transformation Assay”indicated that AZT was likely to cause cancer. In Chernov's summary:
Chernov was concerned that in the rush to approve AZT, the FDA was violating its own guidelines and proceeding on the basis of inadequate information:
Taking into account all of the information available to him, Chernov recommended that AZT should not be approved for marketing:
Obviously if AZT is going to be prescribed to healthy (if “HIV-infected”) people, with the expectation that they will take the drug for the rest of their lives, it is important and ethically imperative that physicians and patients be fully informed on the issue of carcinogenicity. But Burroughs Wellcome and their accomplices in the FDA have done their best to sweep carcinogenicity under the rug. Back in 1986 Burroughs Wellcome proposed dealing with the results of the Cell Transformation Assay by saying on the Retrovir label, “The significance of these in vitro results is not known.”
This proposed labelling was criticized by the FDA toxicology analyst, Harvey Chernov, for being misleading:
Burroughs Wellcome resolved this problem by simply dropping the offending sentence, with the end result being every bit as obscurantist. In the Retrovir entry in Physicians' Desk Reference, written by Burroughs Wellcome, carcinogenicity is dealt with in the following way:
Well now, how many physicians would know what these findings meant? Damned few, if any. Chernov said what the findings meant: AZT is presumed to be a carcinogen! But most physicians would assume that AZT was not carcinogenic, for the simple reason that the Physicians’ Desk Reference entry hadn't said it was.
In toxicology a basic distinction is made between acute toxicity and chronic toxicity. Acute toxicity refers to those adverse effects that are manifest within a relatively short period of time (if not necessarily immediately). Chronic toxicity refers to adverse effects that only become apparent over time. It is a truism of toxicology that chronic toxicity cannot be predicted from acute toxicity.
There are several kinds of chronic toxicity. In one kind, a single exposure to the substance can result in illness many years later – this appears to be the case with Agent Orange (dioxin). Another kind of chronic toxicity involves an accumulation of the substance within the body, after which symptoms occur. Still another kind of chronic toxicity, involves the accumulation of injury:
It takes time to determine the potential of a substance to cause cancer. This is one reason why Chernov objected to the approval of AZT before the completion of long-term carcinogenicity studies. In the words of a toxicology expert:
The point regarding “low dosages”is especially relevant in the case of AZT. Many PWAs have been led to believe that if they are on low dosages of AZT, they will evade the terrible toxicities of the drug. Perhaps they will to some extent evade the acute toxicities, but only time will tell what chronic toxicities lie in wait, including cancer.
Samuel Broder of the National Cancer Institute (NCI) is the man who is more responsible than anyone else for the development and promotion of AZT. (For this role, molecular biologist Peter Duesberg has nominated Broder for the annual Dr. Josef Mengele award.) Even Broder now admits that his drug may cause cancer. He is co-author of a recently published article in the New England Journal of Medicine (NEJM), in which it is stated:
Having made this admission, the authors engage in some strangely sophistical reasoning: “Zidovudine may be associated with a higher incidence of cancers in patients whose immunosurveillance mechanisms are disturbed, simply because it increases their longevity.” Of course, other things being equal, increased longevity increases one's risk for all kinds of things, including perishing in an earthquake, dying of old age, or having dinner with an anti-porn feminist. However, Broder & Company are wrong to assert that AZT increases longevity, for “patients whose immunosurveillance mechanisms are disturbed”. I challenge them, or anyone else, to cite a single, scientifically credible study, that proves this.
As mentioned above, there is no official, on-going surveillance of AZT's side effects. Nevertheless, we have a pretty good idea what some of them are from the PWA grapevine. And occasionally some unofficial side effects surface in letters to medical journals or in off-the-cuff comments at AIDS conferences. One such side effect is muscular atrophy coupled with intense muscular pain. Many PWAs have experienced this condition. For example, Peabody in San Francisco wrote:
Another PWA, Diogenes, wrote:
Instances of severe muscular atrophy and pain caused by AZT were reported in a letter to the New England Journal of Medicine. The physicians observed:
The physicians held AZT responsible for the muscular atrophy and pain:
A leading British AIDS doctor, Dr. Matthew Helbert, sent Burroughs Wellcome stock into a temporary tailspin when be publicly commented on muscular atrophy and other serious, but not officially acknowledged, side effects of AZT:
Other well-known, but not officially acknowledged, side effects of AZT include damage to the kidneys, liver, and nerves. An old friend of mine was one of the earlier patients to be put on AZT. Everyone thought he was doing well. For almost a year he was occasionally able to work or go to concerts. Then one day he went into complete paralysis, and he died two days later. Now, paralysis is not an officially recognized side effect of AZT; there is no warning about it on the package. Nevertheless, there is a connection.
Peter Duesberg has repeatedly referred to AZT as a “poison”, and with good reason. AZT is cytotoxic – it kills cells. AZT terminates DNA synthesis, the very life process itself, by which new cells are formed and grow. It is in the very nature of AZT to kill healthy cells. Therefore, damage to the muscles, to the nerves, and to each and every organ of the body should be considered expected consequences of AZT therapy.
I believe that history will severely condemn the ethical shortcomings of such AZT promoters as Samuel Broder, Anthony Fauci, and Margaret Fischl. In their zeal to expand the market for AZT, they have unconscionably failed to inform the public about the likely long-term consequences of AZT therapy.
I also believe that history will condemn the physicians, “AIDS groups”and individuals who have been urging healthy (“HIV- infected”) gay men to take AZT.
Two years ago I wrote in the Native that “It is malpractice for physicians to prescribe AZT, a poison which can only harm the patient.”[Note 14] I reaffirm this judgment. When physicians coax and cajole and bully their “HIV-positive”patients into taking AZT, do they tell them that the long-term effects of AZT are unknown?...that AZT is cytotoxic?...that AZT destroys bone marrow?...that AZT causes muscular atrophy and pain?...that AZT terminates DNA synthesis?...that AZT damages the nerves, kidneys, and liver? Do they tell their patients that AZT will probably cause cancer in the long run? If not, these physicians have failed to inform their patients about the dangers of a drug whose “benefits”have yet to be demonstrated.
And I issue this challenge to the AZT doctors. If you know of a single scientifically credible study – just one – which proves that AZT is beneficial – for PWAs, for people with ARC, for healthy (“HIV-infected”) people, or for anyone else – then let me know. I would certainly acknowledge it publicly.
Dr. Joseph Sonnabend has said that “AZT is incompatible with life.” In a recent conversation Sonnabend said that Fauci, Fischl, and the other AZT advocates have been remiss, and indeed criminally negligent, in not mentioning the likelihood that long- term use of AZT may result in cancer. I believe that ten years from now, looking back over tens of thousands of horrible, AZT- related deaths, no reasonable person will disagree with his verdict.
1. John Lauritsen, “AZT on Trial: Did the FDA Rush to Judgment – And Thereby Further Endanger the Lives of Thousands of People?”, New York Native, Issue 235, 19 October 1987. Another highly critical review of the Phase II trials was written by Joseph A. Sonnabend, “Review of AZT Multicenter Trial Data Obtained Under the Freedom of Information Act by Project Inform and ActUp”, privately published, New York City, 1987.
2. Terri Creagh-Kirk et al., “Survival Experience Among Patients With AIDS Receiving Zidovudine [AZT]: Follow-up of Patients in a Compassionate Plea Program”, Journal of the American Medical Association, 25 November 1988.
3. John Lauritsen, “On The AZT Front: Part Two”, New York Native, 16 January 1989.
4. Morton Mintz, “Anatomy of a Tragedy”, New York Newsday, 3 October 1989.
5. Harvey I. Chernov, Ph.D., Review & Evaluation of Pharmacology & Toxicology Data, NDA 19-655, 29 December 1986. (FDA document obtained under the Freedom Of Information Act).
7. Louis J. Casarett, “Toxicologic Evaluation”, a chapter in Toxicology: The Basic Science of Poisons, edited by Louis J. Casarett, Ph.D., and John Doull, M.D., Ph.D., New York, Toronto, and London, 1975.
8. John H. Weisburger, “Chemical Carcinogenesis”, a chapter in Casarett and Doull, op. cit.
9. Robert Varchoan, Hiroaki Mitsuya, Charles E. Myers, and Samuel Broder, “Clinical Pharmacology of 3'-Azido-2'3'-Dideoxythymidine (Zidovudine) and Related Dideoxynucleosides”, New England Journal of Medicine, 14 September 1989.
10. Communication from Peabody, Public Forum, AIDS Information Bulletin, San Francisco: (415) 626-1246 [1200 baud] or (415) 626- 3518 [2400 baud].
11. Communication from Diogenes, ibid..
12. Laura J. Bessen et al., “Severe Polymyositis-Like Syndrome Associated With Zidovudine Therapy of AIDS and ARC”(letter), New England Journal of Medicine, 17 March 1988.
13. Duncan Campbell, “The Amazing Aids Scam”, The New Statesman, 24 June 1988.
14. John Lauritsen, “AZT on Trial...”
“The Board found that, in those participants with fewer than 500 T4 cells who received zidovudine [AZT], the rate of progression to AIDS or severe ARC was roughly half that for participants with fewer than 500 T4 cells who received placebo. Progression to symptoms was about the same in patients receiving either 500 mg per day of 1,500 mg per day of the drug. Toxicities were minimal in both treatment groups. More importantly, with the exception of nausea that occurred in about 3 percent of the volunteers, virtually no differences in side effects were observed in persons receiving the lower dose and persons receiving placebo.”
(From press release, U.S. Department of Health and Human Services, 17 August 1989)
What were the actual results?
“Zidovudine [AZT] delayed the onset of advanced ARC or AIDS for individuals who entered the study with less than 500 T4 cell counts. As of August 10, 1989, 38 individuals randomized to placebo had developed endpoints (33 of which were AIDS). Only 17 individuals randomized to 100 mg zidovudine five times daily had developed endpoints (11 of which were AIDS), and 19 individuals receiving 300 mg five times daily developed endpoints (14 of which were AIDS). The substantial difference in outcome between treatment groups was observed for those entering the study with a T4 cell count less than 500. However, for individuals entering with T4 cell counts between 500 and 800, fewer endpoints occurred, and no definite statement regarding differences in event rates can be made at this time.”
(From /Backgrounder: ACTG 019 - Questions and Answers, National Institute of Allergy and Infectious Diseases, 17 August 1989)
| Total | Treatment | |||||
| Sample * (?) |
AZT (?) |
Placebo (?) |
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| # | % | # | % | # | % | |
| Progressed to AIDS or Advanced ARC ** | ? | ? | ? | ? | ? | ? |
| Duration of Treatment: | ||||||
| Range (months) | (?) | (?) | (?) | |||
| Mean (months) | (?) | (?) | (?) | |||
| Median (months) | (?) | (?) | (?) | |||
*According to NIAID, “more than 3200 asymptomatic HIV-infected volunteers”were enrolled “approximately two years ago”. However, all studies have drop-outs. NIAID does not state how many volunteers were still participating when the study was terminated.
**Also sometimes referred to as “severe ARC” neither term has ever been defined.
Copyright © John Lauritsen,