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

Gilles Wandeler, 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2225-2232
Number of pages8
JournalAIDS
Volume27
Issue number14
DOIs
StatePublished - Sep 10 2013

Keywords

  • Cohort study
  • First-line antiretroviral therapy
  • Immunological recovery
  • Southern Africa
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Wandeler, G., Gsponer, T., Mulenga, L., Garone, D., Wood, R., Maskew, M., Prozesky, H., Hoffmann, C., Ehmer, J., Dickinson, D., Davies, M. A., Egger, M., & Keiser, O. (2013). Zidovudine impairs immunological recovery on first-line antiretroviral therapy: Collaborative analysis of cohort studies in southern Africa. AIDS, 27(14), 2225-2232. https://doi.org/10.1097/QAD.0b013e328362d887