The Nucleoside Backbone Affects Durability of Efavirenz- or Nevirapine-Based Highly Active Antiretroviral Therapy in Antiretroviral-Naive Individuals

Objectives: We wished to determine the efficacy of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in antiretroviral-naive patients commencing highly active antiretroviral therapy (HAART) and to evaluate the effect of calendar year, nucleoside analogue reverse trapscriptase inhibitor (NRTI) backbone, sex, and ethnicity on treatment outcome. Methods: Antiretroviral-naive individuals commencing efavirenz or nevirapine with dual-nucleoside analogue backbones were identified from a prospective database. Virological success was defined as HIV viral load <500 copies per milliliter. Treatment failure was defined as a switch or discontinuation of NNRTI or documented virological failure (2 measurements with viral load >500 copies/mL). Results: From a cohort of 994 individuals, 73% commenced efavirenz- and 27% nevirapine-containing regimens. We found no differences between the 2 treatment groups for the time to virological success (proportion with virological success: efavirenz 71%, nevirapine 72%, P = 0.77) or treatment failure (proportion failing treatment: efavirenz 23%, nevirapine 26%, P = 0.58). There was a significant difference in the calendar year for commencing HAART for the time to virological success and treatment failure (P < 0.001). In the multivariable model, the likelihood of virological success for stavudine/lamivudine was 52% [relative hazard (RH) 1.52, 95% confidence interval (CI) 1.17 to 1.97, P = 0.002]. The nonthymidine analogue backbones as a group seemed to be least likely associated with virological success (RH 0.62, 95% CI 0.48 to 0.80, P < 0.001). This was however largely driven by tenofovir/didanosine being significantly associated with treatment failure (RH 6.48, 95% CI 3.81 to 11.0, P < 0.001). Sex and ethnicity were not associated with treatment outcome. Conclusions: We found no significant differences between nevirapine and efavirenz for the time to virological success or treatment failure. Calendar year of commencing HAART and NRTI backbones were significant predictors of virological success and treatment failure, explaining differences in data to the 2NN study. The weaker the NNRTI (or the weaker the protease inhibitor) the more important the NRTI backbone becomes.