title: Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART.
abstract: OBJECTIVE
  To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir).
  
  
  METHODS
  Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32.
  
  
  RESULTS
  A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing.
  
  
  CONCLUSIONS
  In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, F-75013, France sidonie.lambert@psl.aphp.fr.
authors.forename: S
authors.initials: S
authors.lastname: Lambert-Niclot
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: George
authors.affiliation: Chelsea and Westminster Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pozniak
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: White
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Schwimmer
authors.affiliation: Gemeinschaftspraxis Jessen-Stein, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Jessen
authors.affiliation: Department of HIV Medicine, Royal Free Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Dunn
authors.affiliation: Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.affiliation: HIV Unit and Retrovirology Laboratory 'Irsicaixa' Foundation, Hospital Universitari Germans Trias i Pujol, UAB, Badalona, Catalonia, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Ifi-institut, an der Asklepios-Klinik St Georg, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Plettenberg
authors.affiliation: Department of Infectious Diseases, Venhaelsan-Sodersjukhuset, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Blaxhult
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Palmisano
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France CHU de Bordeaux, Pôle de Santé Publique, Service d'Information Médicale, Bordeaux, France Université de Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Wittkop
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, F-75013, France.
authors.forename: V
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, F-75013, France.
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: CMIT, 46 Rue Henri Huchard, 75018 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Raffi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents