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. 2013 Sep 10;27(14):2225-32.
doi: 10.1097/QAD.0b013e328362d887.

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

Gilles Wandeler  1 , Thomas Gsponer, Lloyd Mulenga, Daniela Garone, Robin Wood, Mhairi Maskew, Hans Prozesky, Christopher Hoffmann, Jochen Ehmer, Diana Dickinson, Mary-Ann Davies, Matthias Egger, Olivia Keiser; IeDEA Southern Africa Collaboration
Affiliations

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

Gilles Wandeler et al. AIDS. .

Abstract

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.

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Conflict of interest statement

Disclosure statement

We declare no conflict of interest

Figures

Figure 1
Figure 1. Estimated CD4 trajectories in patients starting first-line ART with and without zidovudine (AZT)
The dotted lines indicate 95% confidence intervals
Figure 2
Figure 2. Adjusted differences in CD4 counts between patients on AZT and those not on AZT after 1 (panel A) and 5 years (panel B) of ART, by cohort
I-squared (p value from test of heterogeneity): 1year (panel A): 58.7% (p=0.013); 5 years (panel B): 87.8% (p<0.001). Analyses were adjusted for sex, age, CD4 and anemia at baseline, calendar year, type of NNRTI and viral load monitoring
See this image and copyright information in PMC

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