Lockman, S and Hughes, M and Sawe, F and Zheng, Y and McIntyre, J and Chipato, T and Asmelash, A and Rassool, M and Kimaiyo, S and Shaffer, D and Hosseinipour, M and Mohapi, L and Ssali, F and Chibowa, M and Amod, F and Halvas, E and Hogg, E and Alston-Smith, B and Smith, L and Schooley, R and Mellors, J and Currier, J
(2012)
Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in africa: A randomized trial.
PLoS Medicine, 9 (6).
15 - ?.
ISSN 1549-1277
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/mm3 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 log10 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/mm3, HIV RNA = 5.2 log10copies/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/mm3. Trial registration: ClinicalTrials.gov NCT00089505. © 2012 Lockman et al.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Lockman, 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 | ekh2@pitt.edu | EKH2 | | | Hogg, E | | | | | Alston-Smith, B | | | | | Smith, L | | | | | Schooley, R | | | | | Mellors, J | jwm1@pitt.edu | JWM1 | | | Currier, J | | | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Deeks, Steven G. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
| Date: |
1 January 2012 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS Medicine |
| Volume: |
9 |
| Number: |
6 |
| Page Range: |
15 - ? |
| DOI or Unique Handle: |
10.1371/journal.pmed.1001236 |
| Refereed: |
Yes |
| ISSN: |
1549-1277 |
| PubMed Central ID: |
PMC3373629 |
| PubMed ID: |
22719231 |
| Date Deposited: |
11 Jul 2012 18:10 |
| Last Modified: |
19 Jun 2021 10:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/12709 |
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