Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial.

TitleNevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial.
Publication TypeJournal Article
Year of Publication2012
AuthorsLockman S, Hughes M, Sawe F, Zheng Y, McIntyre J, Chipato T, Asmelash A, Rassool M, Kimaiyo S, Shaffer D, Hosseinipour M, Mohapi L, Ssali F, Chibowa M, Amod F, Halvas E, Hogg E, Alston-Smith B, Smith L, Schooley R, Mellors J, Currier J
Corporate AuthorsOCTANE(Optimal Combination Therapy After Nevirapine Exposure) ACTG A5208/OCTANE Study Team
JournalPLoS Med
Volume9
Issue6
Paginatione1001236
Date Published2012
ISSN1549-1676
KeywordsAdult, Africa, Anti-HIV Agents, CD4 Lymphocyte Count, Death, Drug Resistance, Viral, Endpoint Determination, Female, HIV Infections, HIV-1, Humans, Kaplan-Meier Estimate, Lopinavir, Medication Adherence, Mutation, Nevirapine, Ritonavir
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.

DOI10.1371/journal.pmed.1001236
Alternate JournalPLoS Med.
PubMed ID22719231
PubMed Central IDPMC3373629
Grant List3U01AI32775-13S5 / AI / NIAID NIH HHS / United States
5 U01 AI069518 / AI / NIAID NIH HHS / United States
5U01AI069455-03 / AI / NIAID NIH HHS / United States
5U01AI069456-03 / AI / NIAID NIH HHS / United States
AI-069501 / AI / NIAID NIH HHS / United States
AI38838 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI69426 / AI / NIAID NIH HHS / United States
AI69453 / AI / NIAID NIH HHS / United States
IAAY1AI8374 / AI / NIAID NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
K24 AI56933 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
U01 AI69463-03 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069436 / AI / NIAID NIH HHS / United States