Protocol 019 of the AIDS Clinical Trails Group is a multicenter, double-blind, placebo-controlled trial of zidovudine (3'-azido-3'-deoxythymidine; formerly AZT) in human immunodeficiency virus-infected asymptomatic individuals. The initial results in the stratum of subjects entering with CD4<R>+</R> cell counts of 0.50×10<R>9</R>/L or less have been reported, but without a detailed a analysis of toxic effects.
This detailed and updated report analyzes the toxic effects that occurred in 1567 subjects (91% men; 89% white) in this stratum of protocol 019 who received placebo (494 subjects), a 500-mg daily dose of zidovudine (544 subjects), or a 1500-mg daily dose of zidovudine (529 subjects). Hematologic, hepatic, and renal effects and patientreported symptoms and clinical signs were monitored.
Severe anemia (hemoglobin level, <80 g/L was associated with both the 500-mg zidovudine group and the 1500-mg500-mg group compared with placebo. The estimated 18month risks of severe anemia were 0.4%, 2.0%, and 9.7% for the placebo, 500-mg zidovudine, and d 1500-mg zi zidovudine groups, respectively. Predictive baseline measures were lower hemoglobin level in the e 1500-mg group and the two zidovudine groups combined and lower platelet count in the 500-mg zidovudine group. The risk of a first severe anemia developing was greatest in months 3 through 8 of treatment. Of the 44 subjects with severe anemia in the zidovudine groups, 18 (41%) progressed from mild anemia (hemoglobin level, 95 to 109 g/L to severe anemia on consecutive visits (usually 2 to 4 weeks apart). Severe neutropenia (absolute neutrophil count, <750×10<R>6</R>/L) did not occur significantly more often in the 500-mg zidovudine group but did in the 1500-mg zidovudine group. Moderate neutropenia (absolute neutrophil count, <1300×10<R>6<R/>/L did develop significantly more often in the 500-mg zidovudine group (165 subjects) than in the placebo group (71 subjects). Mild (or worse) elevations of bilirubin levels were uncommon but occurred more often with zidovudine. Severe nausea (and/or vomiting) was rare (2.8% of subjects) but was associated with zidovudine. Milder patientreported events were common, and a number were associated with zidovudine.
Zidovudine at the 500-mg/d dosage appears to be tolerable in many patients with asymptomatic human immunodeficiency virus infection and CD4<R>+</R> cell counts of 0.50 × 10<R>9</R>/L or less. Increased clinical surveillance for anemia may be warranted in certain patients.(Arch Intern Med. 1992;152:2286-2292)
Koch MA, Volberding PA, Lagakos SW, Booth DK, Pettinelli C, Myers MW. Toxic Effects of Zidovudine in Asymptomatic Human Immunodeficiency Virus-Infected Individuals With CD4<R>+</R> Cell Counts of 0.50×10<R>9</R>/L or Less: Detailed and Updated Results From Protocol 019 of the AIDS Clinical Trials Group. Arch Intern Med. 1992;152(11):2286–2292. doi:10.1001/archinte.1992.00400230094016
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