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By John Lauritsen
New York Native 19 Oct. 1987

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I argued in a previous article (Native #215) that the theory behind AZT (now known by its trade name of Retrovir) was false, inasmuch as the hypothesis that HIV causes AIDS has been refuted by Prof. Peter H. Duesberg, a world-renowned molecular biologist at Berkeley; that AZT's alleged benefits were not backed up by reliable evidence; that its toxicities were firmly established and severe; and that therefore the drug should not be prescribed, recommended, or used.

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Owing to the early termination, only 15 patients (5% of the total) completed the full 24 weeks of treatment. Twenty-three patients were treated for less than four weeks. On the average, patients had received treatment for about 17 weeks at the time the study was aborted. (See Table 1.)

As might be imagined, the premature termination invalidated the original study design and caused chaos from an analytical standpoint. Tables which would have been entirely straightforward if all patients had finished their 24 weeks of treatment had to rely upon controversial statistical projections. For example, instead of showing the percentages of patients in each group who experienced opportunistic infections during the 24 weeks, it became necessary to develop a projected probability of their experiencing opportunistic infections within 24 weeks. This is analogous to estimating the probability of developing arthritis by the age of 70, using a sample in which only a few people had reached this age, and in which some were still teenagers. The method used (Kaplan-Meier Product-Limit Method) is a statistical attempt to estimate what results would have been if the study had not been terminated. Like mopping up milk, it may be the best thing to do-but it would be better not to spill the milk.

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The mortality data that so dazzled the FDA that they terminated the AZT trial prematurely and accepted bad data are shown in Table 2.

Only 1% of the 145 AZT patients, compared to 14% of the 137 placebo patients died during the course of the trial. Statistically, this is highly significant-the probabilities are better than 99 out of 100 that the difference (1% vs. 14%) is real, as opposed to being a product of chance.

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In addition, the death rate in the AZT group is suspiciously low when compared with other trials of AZT. After the "double-blind, placebo-controlled" study was terminated, all patients were informed which treatment they had been receiving, and were offered the option of receiving AZT. (See Table 3)

A total of 227 patients accepted the offer, and continued or began to receive AZT (127 who were originally treated with AZT and 100 who were originally treated with placebo). AZT no longer prevented patients from dying. In the 21 weeks of the "open-label" trial, 10% of the patients died. Curiously, not only deaths but also opportunistic infections increased in the original AZT group as soon as the first study was terminated. There is no good explanation why this should be so.

Another trial of AZT occurred prior to the "double-blind, placebo-controlled" trial. (See Table 4) This was a "Phase I" trial, intended to give a preliminary estimate of the drug's toxicities. In the Phase I trial, 12% died during a time period of only 6 weeks. The four patients who died were replaced, and all 33 patients continued to take AZT in an "extended trial", during which an additional 21% died. It is unclear from the FDA material exactly how long the extended trial lasted-but at any rate a cumulative total of one-third (33%) of the patients died, either in the phase I or in the extended trial.

Burroughs-Wellcome provided data to the FDA on deaths which occurred among patients who began taking AZT following release of the drug. The information was in incredibly garbled form, but I was able to ascertain at least the deaths that occurred during the first 8 weeks of treatment. During this short time period 6% of the patients died. Table 5 shows a comparison of these four studies of AIDS or advanced ARC patients who were treated with AZT.

It can readily be seen that the death rate in the "double-blind, placebo-controlled" trial (the first column) is significantly lower than in any of the other studies, especially considering that the trials in columns three and four represented much shorter time periods. In other words, the mortality data from the "double-blind, placebo-controlled" trial are almost certainly wrong, based on comparisons with mortality data from other AZT trials.

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AZT patients suffered from many adverse reactions to the drug, the most severe involving blood toxicities. These are summarized in Table 6. In less than 18 weeks of treatment, on the average, almost one-third (31%) of the AZT patients required at least one transfusion; one-fifth (21%) of them required multiple transfusions.

Marrow suppression was experienced by 45% of the AZT patients, but only 12% of the placebo patients. Macrocytosis (enlarged red blood cells, associated with pernicious anemia) occurred in 69% of the AZT patients, but in none of the placebo patients. This measure, which clearly distinguished AZT from placebo patients in over two-thirds of the cases, played a major role in the unblinding of the study among the doctors.

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