Journal Article

Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial

Alston-Smith, Beverly, Sawe, Fred, Hosseinipour, Mina, Smith, Laura, Mellors, John, Chipato, Tsungai, Shaffer, Douglas, Halvas, Elias, Schooley, Robert, Amod, Farida, Hughes, Michael, Mohapi, Lerato, Zheng, Yu, Kimaiyo, Sylvester, Hogg, Evelyn, McIntyre, James, Chibowa, Margret, Asmelash, Aida, Rassool, Mohammed, Ssali, Francis, Currier, Judith, Lockman, Shahin

2012

Overview

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. 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. 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). ClinicalTrials.gov NCT00089505.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Africa / Anti-HIV Agents - adverse effects / Anti-HIV Agents - pharmacology / Anti-HIV Agents - therapeutic use / Antiretroviral drugs / Antiviral agents / Care and treatment / CD4 Lymphocyte Count / Comparative analysis / Conferences / Death / Demographic aspects / Drug Resistance, Viral - drug effects / Drug Resistance, Viral - genetics / Drug therapy / Endpoint Determination / Female / Grants / Health aspects / HIV / HIV infection / HIV Infections - diagnosis / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - virology / HIV-1 - drug effects / HIV-1 - physiology / Human immunodeficiency virus / Humans / Infection control / Kaplan-Meier Estimate / Lopinavir - adverse effects / Lopinavir - pharmacology / Lopinavir - therapeutic use / Medication Adherence / Medicine / Methods / Mortality / Mutation - genetics / Nevirapine - adverse effects / Nevirapine - pharmacology / Nevirapine - therapeutic use / Pharmaceutical industry / Physiological aspects / Ritonavir - adverse effects / Ritonavir - pharmacology / Ritonavir - therapeutic use