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 : Please see later in the article for the Editors' Summary
Vyšlo v časopise: Nevirapine- Versus Lopinavir/Ritonavir-Based Initial Therapy for HIV-1 Infection among Women in Africa: A Randomized Trial. PLoS Med 9(6): e32767. doi:10.1371/journal.pmed.1001236 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001236
1. WHO 2010 Antiretroviral therapy for HIV infection in adults and adolescents: Recommendations for a public health approach. 2010 Revision Geneva World Health Organization
2. ReyDHoenBChavanetPSchmittMPHoizeyG 2009 High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. J Antimicrob Chemother 63 380 388
3. LapadulaGCostarelliSQuiros-RoldanECalabresiAIzzoI 2008 Risk of early virological failure of once-daily tenofovir-emtricitabine plus twice-daily nevirapine in antiretroviral therapy-naive HIV-infected patients. Clin Infect Dis 46 1127 1129
4. CiaranelloALLockmanSFreedbergKAHughesMChuJ 2011 First-line antiretroviral therapy after single-dose nevirapine exposure in South Africa: a cost-effectiveness analysis of the OCTANE trial. AIDS 25 479 492
5. LockmanSHughesMDMcIntyreJZhengYChipatoT 2010 Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med 363 1499 1509
6. PetoRPikeMCArmitagePBreslowNECoxDR 1976 Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer 34 585 612
7. ReekieJReissPLedergerberBSedlacekDParczewskiM 2011 A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study. HIV Med 12 259 268
8. SorianoVArastehKMigroneHLutzTOpravilM 2011 Nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients: the ARTEN Trial. Antivir Ther 16 339 348
9. MarconiVCSunpathHLuZGordonMKoranteng-ApeagyeiK 2008 Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa. Clin Infect Dis 46 1589 1597
10. OrrellCWalenskyRPLosinaEPittJFreedbergKA 2009 HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Antivir Ther 14 523 531
11. WallisCLMellorsJWVenterWDSanneIStevensW 2010 Varied patterns of HIV-1 drug resistance on failing first-line antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 53 480 484
12. WallisCLMellorsJWVenterWDSanneIStevensW 2011 Protease inhibitor resistance is uncommon in HIV-1 subtype C infected patients on failing second-line lopinavir/r-containing antiretroviral therapy in South Africa. AIDS Res Treat 2011 769627
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