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


RESULTS
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).


BACKGROUND
ClinicalTrials.gov NCT00089505.
Brigham and Women's Hospital, Boston, Massachusetts, United States of America. slockman@hsph.harvard.edu
Shahin
S
Lockman
Michael
M
Hughes
Fred
F
Sawe
Yu
Y
Zheng
James
J
McIntyre
Tsungai
T
Chipato
Aida
A
Asmelash
Mohammed
M
Rassool
Sylvester
S
Kimaiyo
Douglas
D
Shaffer
Mina
M
Hosseinipour
Lerato
L
Mohapi
Francis
F
Ssali
Margret
M
Chibowa
Farida
F
Amod
Elias
E
Halvas
Evelyn
E
Hogg
Beverly
B
Alston-Smith
Laura
L
Smith
Robert
R
Schooley
John
J
Mellors
Judith
J
Currier
D000328:Adult; D000349:Africa; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003643:Death; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D023381:Endpoint Determination; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D061466:Lopinavir / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055118:Medication Adherence; D009154:Mutation / Q000235:genetics; D019829:Nevirapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D061466:Lopinavir; D019829:Nevirapine; D019438:Ritonavir