title: Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.
abstract: BACKGROUND
  Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP).
  
  
  METHODS
  We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP.
  
  
  RESULTS
  Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome.
  
  
  CONCLUSIONS
  TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
authors.forename: Albert
authors.initials: A
authors.lastname: Mwango
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Giganti
authors.forename: Izukanji
authors.initials: I
authors.lastname: Sikazwe
authors.forename: Crispin
authors.initials: C
authors.lastname: Moyo
authors.forename: Linnaea
authors.initials: L
authors.lastname: Schuttner
authors.forename: Lloyd B
authors.initials: LB
authors.lastname: Mulenga
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bolton-Moore
authors.forename: Namwinga T
authors.initials: NT
authors.lastname: Chintu
authors.forename: Robert
authors.initials: R
authors.lastname: Sheneberger
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Stringer
authors.forename: Jeffrey S A
authors.initials: JS
authors.lastname: Stringer
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000068698:Tenofovir; D015024:Zambia / Q000453:epidemiology; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine