title: Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort.
abstract: BACKGROUND
  Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir-lamivudine plus nevirapine is used in many resource-constrained settings.
  
  
  METHODS
  This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression.
  
  
  RESULTS
  A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis.
  
  
  CONCLUSIONS
  Compared with zidovudine-lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.
authors.affiliation: Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
authors.affiliation: Center for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Eisen
authors.affiliation: Center for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Darin
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.
authors.forename: Seema T
authors.initials: ST
authors.lastname: Meloni
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Rawizza
authors.affiliation: Departments of Biostatistics and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tchetgen Tchetgen
authors.affiliation: Department of Medicine, University of Jos and Jos University Teaching Hospital.
authors.forename: Oche O
authors.initials: OO
authors.lastname: Agbaji
authors.affiliation: Clinical Sciences Division, Nigerian Institute of Medical Research, Yaba.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Onwujekwe
authors.affiliation: Department of Medicine, University of Maiduguri Teaching Hospital.
authors.forename: Wadzani
authors.initials: W
authors.lastname: Gashau
authors.affiliation: Department of Medicine, 68 Military Hospital, Yaba (formerly, at the time of this work).
authors.forename: Reuben
authors.initials: R
authors.lastname: Nkado
authors.affiliation: AIDS Prevention Initiative Nigeria, Ltd./Gte., Abuja, Nigeria.
authors.forename: Prosper
authors.initials: P
authors.lastname: Okonkwo
authors.affiliation: Center for Global Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Kanki
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage*; D012189:Retrospective Studies; D000068698:Tenofovir / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage*
chemical_list: D044966:Anti-Retroviral Agents; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir
keywords: antiretroviral therapy; nevirapine; tenofovir; virologic failure; zidovudine