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

Research output: Contribution to journalArticle

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.

Details

Authors
  • François Raffi
  • Abdel G. Babiker
  • Laura Richert
  • Jean-Michel Molina
  • Elizabeth C. George
  • Andrea Antinori
  • Jose R Arribas
  • Jesper Grarup
  • Fleur Hudson
  • Christine Schwimmer
  • Juliette Saillard
  • Cédrick Wallet
  • Per O. Jansson
  • Clotilde Allavena
  • Remko Van Leeuwen
  • Jean-François Delfraissy
  • Stefano Vella
  • Geneviève Chêne
  • Anton Pozniak
  • NEAT001/ANRS143 Study Group
Organisations
External organisations
  • University College London
  • Lazzaro Spallanzani National Institute for Infectious Diseases
  • ANRS - France Recherche Nord & Sud Sida-HIV Hépatites virales
  • University of Nantes
  • Amsterdam Institute for Global Health and Development
  • Bicêtre Hospital
  • Istituto Superiore di Sanità
  • Chelsea and Westminster Hospital
  • Academic Medical Center
  • University of Bordeaux
  • Saint-Louis Hospital, Paris
  • Paris Diderot University
  • University Hospital La Paz
  • Copenhagen University Hospital
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine

Keywords

  • Adenine, 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, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)1942-51
Number of pages10
JournalThe Lancet
Volume384
Issue number9958
Publication statusPublished - 2014 Nov 29
Publication categoryResearch
Peer-reviewedYes