Superior Effectiveness of Zidovudine Compared with Tenofovir When Combined with Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort

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.