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Dr. Bennett wrote:
"The lack of triphosphorylation reference is from the Perth Group, and I'm inclined to reject that out of hand for the following simple reason: if you put AZT into a virus culture it prevents replication unless resistance mutations exist in the virus. Clearly it MUST be active..."
Dr. Bennett should know better than to assume that IN VITRO is the same IN VIVO. The IN VIVO concentrations of the ACTIVE form of AZT, AZTTP, are insufficient to have an antiretroviral effect.
In an article published in Nature Medicine 1997, researchers recognized that only the AZTTP form of AZT has an 'antiretroviral' property, "Azidothymidine triphosphorylate (AZT-TP) inhibits the viral RT by competing with endogenous thymidine triphosphorylate (TTP)."(1)
However, they go on to say, "Although AZT is converted to AZT-MP with nearly the same efficiency as the thymidine is converted to TMP, the conversion of AZT-MP to AZT-TP is less than one percent the efficiency of the TMP to TTP conversion.... The end result is an accumulation of high concentrations of the inactive AZT-MP but not of the active AZT-TP" (1).
Other research groups have recognized the triphosphorylation problem and have put forward proposals to account for the inability to achieve 'effective concentration of AZT-TP within cells sufficient to suppress HIV replication' (2–4)
I could go on page after page describing toxicities and 'side effects' (rather, primary effects) of AZT. Suffice it to say, the Concorde trials should have led to termination of AZT as a so-called 'therapy'.
"Extended follow-up of patients in one [AZT] trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early... where is the evidence that for a patient with a CD4 count of 450 cells per cubic millimeter and a low plasma viral level, it would not be better to wait before initiating therapy?...In 1990...a patient with a CD4 count of 450 cells per cubic millimeter would have been advised to start monotherapy with zidovudine. We now tell such a patient that, in fact, follow-up data for up to 4.5 years since that time have shown no survival benefit ” (5)
That these researchers would 'counsel' patients that AZT confers 'no survival benefit' is rather dishonest. Had they been more forthright, they would have informed patients that, 'early treatment will increase your risk of death and illness'.
And so perhaps I should ask Dr. Bennett since Christopher Noble has
continued to evade answering this question. If one considers;
1. Hazuda D, Kuo L. (1997). Failure of AZT: A molecular perspective. Nat.
Med., 3, 836-837.
Competing interests: None declared