AZT WATCH New research does not prove efficacy

By John Lauritsen

New York Native 10 May 1990

This article will review a number of recent developments on the AZT front: the expression of skepticism about AZT's alleged "benefits" in the pages of the Journal of the American Medical Association, the long-awaited scientific report on ACTG Protocol 019 in the New England Journal of Medicine, and a major advertising campaign being launched by AZT's manufacturer, Burroughs Wellcome, as well as some provocative thoughts on the role AZt may play in causing "AIDS" from molecular biologist Dr. Peter Duesberg (Professor at the University of California, Berkeley).

Skepticism in JAMA

Two of the leading American medical journals, the New England Journal of Medicine NEJM and the Journal of the American Medical Association JAMA have played especially reprehensible roles in promoting AZT, both through uncritical editorials and through the publication of substandard research allegedly demonstrating AZT's benefits. I have exposed the worthlessness of several of these studies in the pages of the Native. It is encouraging, therefore, to find some good, healthy skepticism about AZT expressed in the pages of JAMA

The "Medical News & Perspectives" section of the 23-30 March 1990 issue of JAMA features an article by Paul Cotton, "Controversy Continues as Experts Ponder Zidovudine's [AZT's] Role in Early HIV Infection". Cotton makes it clear that scientists are far from unanimous in endorsing the recent FDA recommendation to give AZT to healthy individuals who have antibodies to HIV and whose CD4 cell count falls below 500. He cites John D. Hamilton, MD, whose study #298, sponsored by the Veteran's Administration, found no demonstrable benefits of any kind from AZT treatment of HIV-positive patients with CD4 cell counts in the 200 to 500 range.

Cotton also indicates that researchers in Europe were not particularly impressed by the data from the National Institute of Allergies and Infectious Diseases (NIAID), which were the basis of the FDA's recommendations:

Maxime Seligmann, MD, protocol chair of the French arm of the Concorde 1 trial of zidovudine in asymptomatic patients, a collaboration with researchers in Great Britain, says his study's data safety monitoring board had concluded that the NIAID data do not justify closing Concorde's placebo arm. "We need more scientific information on long-term effects, quality of life, survival, and toxicity," he says.

Cotton lists a number of unanswered questions regarding AZT's alleged benefits for healthy persons with HIV antibodies:

Skeptics point out that, according to the NIAID data, 100 patients must take zidovudine for a year to prevent four infections, which for the most part can be treated by other means. Everyone agrees that questions of long-term benefit, survival, toxicity, and resistance to the drug are unanswered. And some doubt the interpretation of temporarily increased CD4 counts as a benefit.

Cotton is to be commended for giving an honest account of scientific differences, and also for referring to HIV as "the retrovirus thought to cause acquired immunodeficiency syndrome (AIDS)" -- which fairly implies that the HIV hypothesis is unproven.

The NEJM Report On Protocol 019

At long last a report has appeared on the NIAID study, ACTG Protocol 019, which was the basis for the FDA recommendation to give AZT to asymptomatic, "HIV-infected" persons. Paul Volberding and Stephen Lagakos are the principal authors of the article, "Zidovudine in Asymptomatic Human Immunodeficiency Virus Infection: A Controlled Trial in Persons with Fewer than 500 CD4-Positive Cells per Cubic Millimeter", (NEJM, 5 April 1990).(1)

The same issue of NEJM features an editorial by Gerald H. Friedland, "Early Treatment for HIV: The Time Has Come"(2), which unctuously praises the research ("The study by Volberding et al. is a strong confirmation of the value of the clinical-trial process."), urges "persons who may be at risk for HIV infection to undergo testing for the virus", and laments the possibility that many of those with "HIV infection" might not be able to obtain AZT.

From my previous experience with AZT-advocacy research, and the unfavorable impression made on me by Volberding and Lagakos at an AZT conference in Washington(3), I had expected that the research would be bad. But I had at least expected it would have a slick, superficial plausibility. Instead, I found such a pathetically blotched job that it is almost embarrassing to write about it. The authors' ignorance of elementary statistics is beyond belief. None of their tables show bases or make sense. Looking at one of their tables, it is impossible to tell either what people or how many people the table is based on. Nor is this information to be found anywhere else in the report.

Volberding et al. compare raw numbers with each other, without indicating the size of the subsamples from which the numbers are drawn. And then, willy-nilly, they compare percents with raw numbers -- something any schoolboy is supposed to know better than to do.

Much of the article consists of crude special pleading. As support for the "benefits" of AZT, the authors cite the fraudulent Phase II Trials(4) and the shoddy AZT survival study(5), along with the utterly ridiculous Pizzo study. (6) However, they don't even mention the far superior Dournon study: a case-control study conducted in France, which found that the very, very slight "benefits" of AZT vanished and were utterly nonexistent after six months.(7)

(In the Pizzo study, researchers connected with the government and roughs Wellcome gave AZT to 21 children who had "HIV infection", and claimed that the AZT boosted their IQs by 15 points. Although 5 of the 21 children died, the researchers were so impressed by "neuro developmental" improvements that they recommended giving AZT to "infected but asymptomatic newborns". Anyone who has studied the principles and techniques of psychological testing can only be appalled by this misuse of intelligence tests.)

Before commenting further on Protocol 019, I consider it my ethical obligation as a journalist to talk to Paul Volberding, to see what explanations or excuses he can offer for this rubbish. So far he hasn't returned my calls.

Hard Sell for AZT

It looks as though Burroughs Wellcome is going to adopt an aggressive marketing strategy for AZT (alias Retrovir, alias zidovudine). A "statgram" dated March 1990 was mailed to thousands of physicians. It described the "benefits" allegedly demonstrated by NIAID's studies, Protocols 016 (AZT treatment of those with "early symptoms of HIV infection") and 019 (AZT treatment of healthy people with "HIV infection"). The statgram urged doctors to evaluate periodically any patient "who tests positive for HIV infection ... until Retrovir, as recommended in the prescribing information, is indicated." A toll-free number was listed for those who wanted to know more.

A recent news item in the Bay Area Reporter, "AZT Maker Planning Ad Blitz", indicates that Burroughs Wellcome is targeting gay men for a major advertising campaign. Market research is being conducted in San Francisco to evaluate the effectiveness of advertising which will promote testing for HIV infection. One objective of the research is to determine whether the advertising would be more effective if it said, "Sponsored by Your Local HIV Support Group" (read GMHC, Project Inform, and the like) or if it said, "Sponsored by Burroughs Wellcome."(8)

Interview with Peter Duesberg

Following is an excerpt from an interview that took place with Peter Duesberg in New York City on 25 March 1990. At a forum the previous evening Duesberg had presented his "Risk-AIDS" hypothesis, which he has formulated as an alternative to the prevailing "HIV-AIDS" hypothesis.(9)

The "Risk-AIDS" hypothesis recognizes that "AIDS" is officially defined by the CDC as any of over two dozen old diseases in the presence of antibodies to HIV, a probably harmless retrovirus. It suggests that different "risk groups" and different individuals may be getting sick in different ways and for different reasons. Therefore, we should examine the risks that impinge on them. There may be very good and even obvious reasons why in travenous drug users, a very small subset of gay men, a very small percentage of hemophiliacs, a minuscule number of transfusion recipients, and a minuscule number of children have gotten sick in ways that qualified for a diagnosis of "AIDS".

John Lauritsen: We should be open-minded, but some how drugs make sense to me [as a cause of AIDS].

Peter Duesberg: It's better than that. We have 30% confirmed IV drug users, recorded by the CDC. That's a very solid link. They are injecting heroin, probably on a daily basis, in millimolar amounts. To ignore that, or not to consider that, as a factor of direct or indirect immune suppression, is from a chemical point of view at least negligent.

JL: or schizophrenic.

PD: And the AZT -- we don't need to ask any further. It was awarded the Nobel prize for killing cells.

JL: This brings up another thing. The AIDS epidemic appears to have peaked already, probably about in the second part of 1988.(10) But if 50,000 or more people with HIV antibodies are taking AZT, then there may be another upswing in incidence, if these people end up being listed as "AIDS cases".

PD: They will have to be. Clearly. They will be perfect AIDS cases. Their immune systems will be intoxicated by AZT and they will be antibody positive. That's the definition of an AIDS case.

JL: Right. And yet it would really be AZT poison ing. Now, let's talk about AZT. They've begun giving it to perhaps tens of thousands of people who are healthy but have HIV antibodies. What's the prognosis going to be for them?

PD: I do not see how they could possibly survive it, in the long run. So the prognosis is clear -- either a fast or a slow death of the immune system, or death altogether, because all growing cells will be killed by incorporation of AZT. AZT is a DNA chain terminator. That's what it was designed for. So I don't think anybody could sustain that for a very long time. Variations may exist in the ability of individuals to take it up, because AZT, in order to get into the cells, needs to be phosphorylated, and that is done by enzymes that are called kinases -- and people apparently differ with regard to kinases -- at least cells in culture do and animals do, and likely people do too. And those who have less kinases won't take AZT up well. They'll essentially piss it out -- luckily. They would be more resistant. And others, who do take AZT up well, would be more sensitive and would be intoxicated much more effectively and much more directly.

JL: A DNA chain terminator -- what are the consequences of this?

PD: It's embarrassingly clear. It is simply stopping the growth of DNA. And you have to complete DNA cell synthesis. Cell division is based on doubling DNA, which is the central molecule of life. It contains all the genetic information. If you don't complete that, the cell is not viable. It will die. The information about an organism is written down in a code that we call DNA, the chromosome or nucleic acid. If that book isn't completely written, you are incomplete, you are not viable. You can only live if everything that is needed for a primate is in every single cell of your body -- that makes you John Lauritsen. If only half a copy is there, then you are no longer John Lauritsen. Then there is only half a cell, and most likely that cell will be dead, because it lacks important things that it needs for its survival.

JL: So basically, the very nature of AZT is to terminate life? Is that too strong?

PD: No. To terminate living cells. And of course to terminate life is a secondary consequence. The primary target is to kill all cells that are in the process of dividing. That's what AZT was developed for, to kill cancer cells. And as we all know, chemotherapy is aimed at growing cells. The benefit is we kill the tumor cells. The heavy price we pay in all chemotherapy is that all normal cells that are growing at the time will also be killed. Fortunately, you can often regenerate the normal cells, and if you are lucky, the tumor will not be regenerated. In reality though, you often get a remission. The tumor will be reduced to a small number of cells, and then will come back. And often then the patient needs a second round of chemother apy.

But the principle is to kill everything that's growing at the time, and hope you wipe out the enemy better than your friends.

JL: I thought that chemotherapy was usually given for a relatively short period of time.

PD: It is. You couldn't sustain it longer. You hope to wipe out in that short time the tumor, and hope for the patient to regenerate.

JL: And yet AZT, a form of chemotherapy, is being given now, on a 24-hour basis, with the idea that people will take it as long as they live.

PD: Yes -- that is simply incomprehensible to me. I cannot come up with a rational explanation. I haven't heard one. In fact, they always avoid one -- they keep saying it has been shown empirically to prolong life. That is very difficult for me to accept. I'm trying to take the data for what they are, and to criticize them on the basis of intrinsic inconsistencies, but this one I simply can't accept. I cannot see how DNA chain termination can prolong life, DNA being the basis of life. How DNA chain termination could prolong life is very difficult for me to understand, in fact, impossible.

JL: I agree, and we know that the Phase II trials were fraudulent. There's no nice way to put it: they were fraudulent. And so, not only is the theory behind AZT wrong, but the "findings" are phoney as well.

Future Scenario: AZT Poisoning = AIDS

When we add it all together, it doesn't look good. In response to a massive propaganda campaign, tens of thousands of gay men and others "at risk" will be tested for HIV antibodies. Doctors for those who "test positive" will monitor their T-cells like a hawk -- probably enough to make anyone sick from sheer anxiety. And if at any time the CD4 count falls below 500, AZT treatment will be initiated to "slow the progression of HIV infection." Sooner or later, AZT poisoning will manifest itself in one of the more than two dozen conditions that qualify for a diagnosis of "AIDS". Eventually, the patient will die of "AIDS". Friends, relatives, and doctors of the deceased will be grateful that at least AZT had helped to "extend life" or "buy a little more time" for him. *

References

1. Paul A. Volberding, Stephen W. Lagakos, et al., "Zidovudine in Asymptomatic Human Immunodeficiency Virus Infection: A Controlled Trial in Persons with Fewer than 500 CD4-Positive Cells per Cubic Millimeter", New England Journal of Medicine , 5 April 1990.

2. Gerald H. Friedland, "Early Treatment for HIV: The Time Has Come" (editorial), NEJM, 5 April 1990.

3. See "A 'State of the Art' AZT Conference", by John Lauritsen, New York Native, Issue 361, 19 March 1990.

4. See "AZT on Trial" by John Lauritsen, New York Native, Issue 235, 19 October 1987.

5. See "On the AZT Front: Part Two" by John Lauritsen, New York Native Issue 300, 16 january 1989.

6. Philip A. Pizzo, et al ., "Effect of Continuous Intravenous Infusion of Zidovudine (AZT) in Children with Symptomatic HIV Infection", NEJM 6 October 1988.

7. E. Dournon et al., "Effects of Zidovudine [AZT] in 365 Consecutive Patients With AIDS or AIDS-Related Complex", The Lancet , 3 December 1988.

8.Dennis Conkin, "AZT Maker Planning Ad Blitz", Bay Area Reporter, 22 March 1990.

9. See Peter Duesberg; "AIDS: Non-Infectious Deficiencies Acquired By Drug Consumption And Other Risk Factors"; Research in Immunology ; 1990, 141 (in press).

10. See "Debate Over AIDS Incidence" by John Lauritsen, New York Native, Issue 363, 2 April 1990.