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Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial.

TitleRitonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial.
Publication TypeJournal Article
Year of Publication2014
AuthorsRaffi F, Babiker AG, Richert L, Molina J-, George EC, Antinori A, Arribas JR, Grarup J, Hudson F, Schwimmer C, Saillard J, Wallet C, Jansson PO, Allavena C, Van Leeuwen R, Delfraissy J-, Vella S, Chêne G, Pozniak A
Corporate AuthorsNEAT001/ANRS143 Study Group
JournalLancet
Volume384
Issue9958
Pagination1942-51
Date Published2014 Nov 29
ISSN1474-547X
KeywordsAdenine, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Cholesterol, HDL, Cholesterol, LDL, Darunavir, Deoxycytidine, Drug Resistance, Viral, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, HIV-1, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Organophosphonates, Pyrrolidinones, Raltegravir Potassium, Ritonavir, Sulfonamides, Tenofovir, Treatment Outcome
Abstract

BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen.

METHODS: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962.

FINDINGS: Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively).

INTERPRETATION: Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL.

FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.

DOI10.1016/S0140-6736(14)61170-3
Alternate JournalLancet
PubMed ID25103176
Grant List097410 / / Wellcome Trust / United Kingdom
MC_U122886352 / / Medical Research Council / United Kingdom