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Actually, the purpose of the Furman study wasn’t to describe an assay as you claim; it was to investigate the relative selectivity of AZT triphosphate for the enzymes you mention. (Their findings in this regard were disproved in a slew of subsequent studies. Genetica 95: 103-109, 1995.) But the relevant bit from their paper was: “IC50 (concentration of inhibitor that inhibits enzyme activity 50%) values were determined for azidothymidine triphosphate with HIV reverse transcriptase…”

Since the Furman study determined the all-important IC50 value of AZTTP, it was entirely “appropriate” to “pick” it. There aren’t any other “later studies” in vitro reporting lower IC50 values for AZTTP that I “ignored”. And not a single one in vivo for “HIV positive subjects.” No doubt because apart from the first one which everyone agrees Toyoshima et al botched, all the studies to which I referred you, “increasing knowledge and experience in the scientific community”, have reported that human cells in vivo triphosphorylate AZT to only miniscule concentrations - far lower than the minimum IC50 value for AZTTP that Furman et al ascertained in vitro for the activated drug to have antiretroviral activity. You can’t waffle your way out of this. You’ve got serious trouble coming and you know it. The kind that Big Tobacco is having in American courts right now.

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Certainly, due to saturation and the other factors that you mention, there are poor correlations between the size of the AZT dose administered and intracellular concentrations of AZT, AZT mono-, di-, and triphosphate. But it is ludicrous to suggest that there is a poor correlation between “AZT [tri-] phosphorylation and antiviral activity.” Because unless AZT is triphosphorylated to its IC50 level, it can’t be antiretroviral. And the more the merrier. But no matter what the dose given, the “later studies” I cited have consistently shown that the cells of patients given AZT cannot triphosphorylate it to levels anywhere near its minimum effective concentration.

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Furman et al speculated: “Incorporation of azidothymidylate [AZTTP] into a growing [proviral HIV] DNA strand should terminate DNA elongation and thus inhibit DNA synthesis.” And thus block HIV replication. That was the idea (which you assert as an established fact). In reality we know AZT doesn’t terminate viral DNA chain synthesis in vivo, because as I explained, it doesn’t reduce HIV DNA levels i.e. “viral burden”, or any other direct marker for HIV infection levels. This is because AZT is not triphosphorylated significantly in the cells of people taking it, evident since the early nineties. And unless the drug is triphosphorylated, it can’t be incorporated into growing viral DNA chains to terminate them.

In short, taken as a medicine, AZT can’t and doesn’t work as claimed. Indeed your own PRODUCT INFORMATION advisory concedes: “The relationship between in vitro susceptibility of HIV to [AZT] and the inhibition of HIV replication in humans or clinical response to therapy has not been established.” Which is another way of saying that you’ve never proved AZT effective as an antiviral medicine. Well precisely.

The question you are going to have to answer sooner or later is this: Knowing that AZT was synthesized in 1961 as a cell poison, why did you commence marketing it as an ‘antiretroviral’ drug in 1987 before proving that it has this latter activity in vivo? And why have you disregarded all studies published since, indicating that it doesn’t. Especially knowing how harmful it is.

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Like all indiscriminate cell poisons such as arsenic and mercury salts in the olden days, AZT might conceivably allay certain infections temporarily, due to its established bactericidal activity. But it can’t be and isn’t antiretroviral for the reasons I’ve set out. You haven’t addressed the fact that the biggest and best conducted AZT trial yet conducted, the Concorde trial, found no therapeutic benefits for asymptomatic HIV-positive patients, and the extended results of the trial found that it increases rather than reduces risk of death. And as you know, numerous other clinical trials conducted independently and not funded by your company have also reported that AZT is at best useless, and at worst accelerates clinical decline and death. Obviously, excuses about “development of resistance” for its clinical inefficacy don’t cut it unless you have established that AZT has some initial anti-HIV activity in vivo. You haven’t.

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It may be that AZT remains the biggest selling AIDS drug (which, together with 3TC, hauled in $1.1 billion last year), and is still recommended by the “AIDS experts” as part of “triple combination therapy” notwithstanding its manifest inefficacy and toxicity. Your drug-marketing budget of $4.7 billion last year alone might have something to do with it. But widespread use doesn’t establish it works, any more than the standard textbook administration of arsenic to scurvy-ridden English sailors and soldiers did. Anyway, facing a mountain of severe toxicity and clinical inefficacy reports, the US Department of Health and Human Services has recently done an about-face on its ‘hit early, hit hard’ treatment recommendations, and on 6 February this year laid down new guidelines urging that the administration of AZT and other ‘antiretrovirals’ be delayed. And as we speak, the British HIV Association is preparing its own treatment guidelines, proposing an even longer delay in the initiation of treatment.

Quoted in Esquire in April 1999 leading US AIDS clinician Dr Michael Saag at the University of Birmingham, Alabama remarked that doctors “should expect failure with whatever [‘antiretroviral’ cocktail they] first use. We should plan on it. We should prepare for it. Clinicians should expect failure.” He noted that instead of getting better, his patients on ‘antiretroviral’ cocktails were dying: “They aren’t dying of a traditionally defined AIDS illness… I don’t know what they’re dying of, but they are dying. They’re just wasting and dying.” The logic may be elusive to the “AIDS experts”, but gee, could it be that cell poisons poison cells?

ANTHONY BRINK