Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events

Abstract

Objective: To describe the safety and tolerability of zidovudine, lamivudine, and efavirenz in a low-income setting.

Design: We conducted a prospective cohort study in a workplace HAART programme in South Africa, which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring 6-monthly pre-HAART and at 2, 6, 12, 24, 36, 48 weeks during HAART.

Methods: We assessed the incidence of specified clinical and laboratory events (AIDS Clinical Trials Group grade 3 or higher) and associated regimen changes, hospitalizations, and deaths one year before HAART initiation and one year on-HAART using person-year analysis.

Results: Between November 2002 and October 2005, 853 subjects (98% male, median age 40 years, and median CD4 cell count at HAART initiation 186 cells/mul) met enrollment criteria. The incidence of events on-HAART was higher than pre-HAART for neutropenia and nausea/vomiting. Dizziness was common early after HAART initiation (not evaluated pre-HAART). Of those with neutropenia, 88% had no apparent clinical consequences. The incidence of anemia, hepatotoxicity, peripheral neuropathy, and rash was similar or higher pre-HAART than on-HAART. Mean hemoglobin rose during the time on-HAART and was higher at 24 and 48 weeks than at baseline (P < 0.001).

Discussion: This regimen was well tolerated with a short-term increase in neutropenia, nausea, and probably neurocerebellar events. Most significantly, in contrast to reports from high-income countries, we observed a long-term improvement in the hemoglobin concentration.

Fig. 1. Proportion at each time interval with grade 3 or 4 laboratory events or any clinical events

(a) Laboratory events. Anemia; neutropenia; hepatotoxicity. (b) Clinical events. Rash; nausea/vomiting; neurocerebellar; neuropathy. Number of subjects evaluated during each time interval: baseline, 853; 2 weeks, 628; 6 weeks, 705; 12 weeks, 661; 24 weeks, 589; 36 weeks, 507; 48 weeks, 451. No baseline neurocerebellar data were available. bl, Baseline; wk, week after HAART initiation.

Fig. 2. Box plot of hemoglobin at baseline and follow-up time intervals

Horizontal line, median; box, interquartile range; whiskers, adjacent values; circles, outlier values. bl, Baseline; wk, week.