title: Non-nucleoside reverse transcriptase inhibitor outcomes among combination antiretroviral therapy-treated adults in Botswana.
abstract: BACKGROUND
  National initiatives offering non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) have expanded in sub-Saharan Africa. The Tshepo study is the first clinical trial evaluating the long-term efficacy and tolerability of efavirenz versus nevirapine-based cART among adults in Botswana.
  
  
  METHODS
  A 3-year randomized study (n = 650) using a 3 x 2 x 2 factorial design comparing efficacy and tolerability among: (i) zidovudine/lamivudine versus zidovudine/didanosine versus stavudine/lamivudine; (ii) efavirenz versus nevirapine; and (iii) community-based supervision versus standard adherence strategies. This paper focuses on comparison (ii).
  
  
  RESULTS
  There was no significant difference by assigned NNRTI in time to virological failure with resistance (log-rank P = 0.14), nevirapine versus efavirenz [risk ratio (RR) 1.54, 95% CI 0.86-2.70]. Rates of virological failure with resistance were 9.6% nevirapine-treated (95% CI 6.8-13.5) versus 6.6% efavirenz-treated (95% CI 4.2-10.0) at 3 years. Women receiving nevirapine-based cART trended towards higher virological failure rates when compared with efavirenz-treated women, Holm-corrected (log-rank P = 0.072), nevirapine versus efavirenz (RR 2.22, 95% CI 0.94-5.00). A total of 139 patients had 176 treatment-modifying toxicities, with a shorter time to event in nevirapine-treated versus efavirenz-treated patients (RR 1.85, 1.20-2.86; log-rank P = 0.0002).
  
  
  CONCLUSIONS
  Tshepo-treated patients had excellent overall immunological and virological outcomes, and no significant differences were observed by randomized NNRTI comparison. Nevirapine-treated women trended towards higher virological failure with resistance compared with efavirenz-treated women. Nevirapine-treated adults had higher treatment modifying toxicity rates when compared with those receiving efavirenz. Nevirapine-based cART can continue to be offered to women in sub-Saharan Africa if patient education concerning toxicity is emphasized, routine safety monitoring chemistries are performed and the potential risk of efavirenz-related teratogenicity is considered.
authors.affiliation: Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education (BHP), Gaborone, Botswana.
authors.forename: C William
authors.initials: CW
authors.lastname: Wester
authors.forename: Ann Muir
authors.initials: AM
authors.lastname: Thomas
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Makhema
authors.forename: Tendani
authors.initials: T
authors.lastname: Gaolathe
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: Victor
authors.initials: V
authors.lastname: deGruttola
authors.forename: Richard G
authors.initials: RG
authors.lastname: Marlink
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D001902:Botswana / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005193:Family Planning Services; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D011247:Pregnancy; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors