Zidovudine impairs immunological recovery on first-line antiretroviral therapy: Collaborative analysis of cohort studies in southern Africa

Objectives: Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4⁺ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa. Design: Cohort study. Methods: Patients aged at least 16 years who started first-line ART in South Africa, Botswana, Zambia, or Lesotho were included. We used linear mixed-effect models to compare CD4⁺ cell count trajectories between patients on ZDV-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4⁺ cell count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4⁺ cell count and hemoglobin level, age, sex, type of regimen, viral load monitoring, and calendar year. Results: A total of 72 597 patients starting ART, including 19 758 (27.2%) on ZDV, were analyzed. Patients on ZDV had higher CD4⁺ cell counts (150 vs.128 cells/μl) and hemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be women than those on other regimens. Adjusted differences in CD4⁺ cell counts between regimens containing and not containing ZDV were -16 cells/μl [95% confidence interval (CI) -18 to -14] at 1 year and -56 cells/μl (95% CI -59 to -52) at 5 years. Impaired immunological recovery was more likely with ZDV compared to other regimens (odds ratio 1.40, 95% CI 1.22-1.61). Conclusion: In southern Africa, ZDV is associated with inferior immunological recovery compared to other backbones. Replacing ZDV with another nucleoside reverse transcriptase inhibitor could avoid unnecessary switches to second-line ART.