AZT impairs immunological recovery on first-line ART: collaborative analysis of cohort studies in Southern Africa


Wandeler G, Gsponer T, Mulenga L, Garone D, Wood R, Maskew M, Prozesky H, Hoffmann C, Ehmer J, Dickinson D, Davies MA, Egger M, Keiser O; for the IeDEA Southern Africa Collaboration


AIDS. 2013 May 8. [Epub ahead of print] PubMed PMID: 23660577



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.


Cohort study.


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.


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).


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

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