Author(s): Lockman S, Hughes M, Sawe F, Zheng Y, McIntyre J,
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Abstract BACKGROUND: Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART. METHODS AND FINDINGS: In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm(3) were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log(10) below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95\% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm(3), HIV RNA = 5.2 log(10)copies/ml. Median follow-up = 118 weeks; 29 (6\%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17\%) in the NVP and 50 (43 VFs, seven deaths; 20\%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95\% CI 0.56-1.29). During initial assigned treatment, 14\% and 16\% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26\% and 22\% experienced grade 3/4 laboratory abnormalities. However, 35 (14\%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32\%) of NVP and 54 (22\%) of LPV/r arms (HR = 1.7, 95\% CI 1.2-2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45\%) of 29 women tested in the NVP versus six (15\%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF. CONCLUSIONS: Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm(3). TRIAL REGISTRATION: ClinicalTrials.gov NCT00089505.
This article was published in PLoS Med
and referenced in Journal of Antivirals & Antiretrovirals