Increased Risk of Sickness and Death with AZT

“participants of open-label ZDV [AZT] still had four to five times the incidence of ARC/AIDS/death of participants on blinded therapy [of which approximately half were on AZT and half on placebo]...The unadjusted hazard of ARC/AIDS/death was 4.6 times higher for participants [in the deferred group] who had received ZDV...after adjustment for latest CD4 this became 1.6...There was a suggestion of a benefit in terms of [slower] progression to ARC, AIDS or death [with AZT], no effect on progression to AIDS or death, and a suggestion of an increase in mortality.”

“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”

“The mortality rate was significantly higher among [a group of 1372] patients who had received antiretroviral therapy [principally AZT] before enrollment in the clinic”

“None of the LTAs [long term asymptomatics] received any antiviral drugs during the study; however, 3 [of 6] rapid progressors…were treated with zidovudine…[and] a rapid progressor was treated with didanosine during the study.”

“despite the evidence that purified [blood clotting] factor VIII is beneficial in maintaining or even increasing T-cell counts, several studies testing purified factor VIII [as opposed to the older forms of Factor VIII which were 99% to 99.9% impurities] are ambiguous about its effectiveness in preventing or treating AIDS. Some of these studies have only tested partially purified, i.e. 2-10 units/mg, instead of highly purified, i.e. 2000-3000 units/mg, factor VIII. But each of the studies that are ambiguous about the benefits have also treated their patients with toxic antiviral DNA chain terminators like AZT. Indeed the study by de Biasi et al. was the only one that has tested purified factor VIII in the absence of AZT. The study by Seremetis et al. initially called for no AZT, but later allowed it anyway. Thus in all but one study, the potential benefits of highly purified factor VIII have been obscured by the toxicity of AZT.”

“Adjusted for baseline CD4 [immune cell counts] and age [correlated with lifetime exposure to clotting factor infusions], subjects [hemophiliacs] who had started on zidovudine [AZT] had increased risks, especially for AIDS [4.46 times greater risk!] and death [2.37 times]”

“Only 38% of the HLP [Healthy long-term positives] had ever used zidovudine [AZT] or other nucleoside analogues, compared with 94% of the progressors.”

“A total of 172 (96 Imm, 76 Def) participants died [169 who had taken some AZT, 3 who had only taken placebo]...The results of Concorde do not encourage the early use of zidovudine in symptom-free HIV-infected adults. They also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy...Representatives of the Wellcome Foundation [Glaxo Wellcome manufactures AZT] who were also members of the Coordinating Committee have declined to endorse this report.”

“Leukopenia [white blood cell deficiency] occurred in 82% of the patients receiving early therapy and 77% of those receiving late therapy [AZT only when AIDS occurred]; 20% and 16%, respectively, had anemia. 14% and 10%, respectively, had severe leukopenia...and 5% and 2% had severe anemia requiring transfusion. Nausea (or vomiting) and diarrhea occurred more frequently in the early-therapy group than in the late-therapy group (40% vs. 23%, respectively; P <0.01)...The dosage of blinded study medication was reduced because of adverse reactions in 64 [38%] of the patients assigned to zidovudine (early therapy) and in 29 [17%] of those assigned to placebo (late therapy)...Once AIDS developed in patients receiving early therapy, more of them tended to have multiple AIDS diagnoses, a slightly higher proportion died, and the median survival time was slightly shorter than in similar patients who received late therapy”

“None of the asymptomatic individuals was receiving zidovudine[AZT]. The CD4 count of patients receiving zidovudine was lower than that of those not receiving the antiviral (mean of 69 and 217/cubic-mm, respectively)…CD4 numbers were significantly lower in patients who developed HIV-related malignancies while receiving zidovudine”

“after starting antiretroviral treatment...the estimated probability of developing lymphoma ...by 36 months, [was] 46.4% (CI, 19.6% to 75.5%)...a direct role of therapy itself cannot be totally discounted...Zidovudine can act as a mutagen”