title: 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.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories.
authors.affiliation: Infectious Diseases Department, University of Nantes, Nantes, France. Electronic address: francois.raffi@wanadoo.fr.
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Babiker
authors.affiliation: Inserm U897 Epidemiologie-Biostatistique, University of Bordeaux, Bordeaux, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Richert
authors.affiliation: Department of Infectious Diseases, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris and University of Paris Diderot, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: George
authors.affiliation: Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: HIV Unit, Internal Medicine Service, Hospital La Paz, Madrid, Spain.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: CHIP Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Grarup
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Fleur
authors.initials: F
authors.lastname: Hudson
authors.affiliation: Inserm U897 Epidemiologie-Biostatistique, University of Bordeaux, Bordeaux, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Schwimmer
authors.affiliation: ANRS, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Saillard
authors.affiliation: Inserm U897 Epidemiologie-Biostatistique, University of Bordeaux, Bordeaux, France.
authors.forename: Cédrick
authors.initials: C
authors.lastname: Wallet
authors.affiliation: CHIP Department of Infectious Diseases and Rheumatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per O
authors.initials: PO
authors.lastname: Jansson
authors.affiliation: Infectious Diseases Department, University of Nantes, Nantes, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.affiliation: Academic Medical Centre, Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
authors.forename: Remko
authors.initials: R
authors.lastname: Van Leeuwen
authors.affiliation: Service de Médecine Interne - Immunologie Clinique, ANRS, CHU de Bicêtre, Paris France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.affiliation: Inserm U897 Epidemiologie-Biostatistique, University of Bordeaux, Bordeaux, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.affiliation: Chelsea and Westminster NHS Foundation Trust, London, UK.
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D000069454:Darunavir; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D063065:Organophosphonates; D011760:Pyrrolidinones; D013449:Sulfonamides; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir; D000069454:Darunavir