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AIDS:
doi: 10.1097/QAD.0b013e328362d887
Clinical Science

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

Wandeler, Gillesa,b; Gsponer, Thomasa; Mulenga, Lloydc; Garone, Danielad; Wood, Robine; Maskew, Mhairif; Prozesky, Hansg; Hoffmann, Christopherh; Ehmer, Jocheni; Dickinson, Dianaj; Davies, Mary-Annk; Egger, Matthiasa,k; Keiser, Oliviaa

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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.

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

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