title: Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: aDivision of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern bDepartment of Infectious Diseases, University Hospital Bern, Bern, Switzerland cCentre for Infectious Disease Research in Zambia, Lusaka, Zambia dKhayelitsha ART Programme, Médecins Sans Frontières, Cape Town eThe Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town fThemba Lethu Clinic, Johannesburg gDivision of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town hAurum Institute for Health Research, Johannesburg, South Africa iSolidarMed Lesotho, Lucerne, Switzerland jHIV private practice, Gaborone, Botswana kSchool of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors: Gilles
authors: G
authors: Wandeler
authors: Thomas
authors: T
authors: Gsponer
authors: Lloyd
authors: L
authors: Mulenga
authors: Daniela
authors: D
authors: Garone
authors: Robin
authors: R
authors: Wood
authors: Mhairi
authors: M
authors: Maskew
authors: Hans
authors: H
authors: Prozesky
authors: Christopher
authors: C
authors: Hoffmann
authors: Jochen
authors: J
authors: Ehmer
authors: Diana
authors: D
authors: Dickinson
authors: Mary-Ann
authors: MA
authors: Davies
authors: Matthias
authors: M
authors: Egger
authors: Olivia
authors: O
authors: Keiser
mesh_terms: D000328:Adult; D000353:Africa, Southern; D000740:Anemia / Q000139:chemically induced; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine
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