title: Highly frequent HIV-1 minority resistant variants at baseline of the ANRS 139 TRIO trial had a limited impact on virological response.
abstract: OBJECTIVE
  To assess the prevalence of minority resistant variants (MRVs) at baseline and their impact on the virological response. The ANRS 139 TRIO trial evaluated the combination of raltegravir, etravirine and darunavir, plus an optimized background therapy, in 87% of cases. Patients were highly experienced and harboured multiresistant viruses, but were naive to the three drugs, and showed a high level of virological suppression.
  
  
  METHODS
  Ultra-deep sequencing of reverse transcriptase, protease and integrase regions was performed at the trial baseline, and sequences were interpreted according to the ANRS algorithm. MRVs were assessed using MiSeq and 454 technologies (limit of detection 1%).
  
  
  RESULTS
  At baseline, minority variants with at least one NRTI, one NNRTI, one PI, one major PI or an integrase inhibitor resistance-associated mutation were present in 46%, 45%, 68%, 24% and 13% of patients, respectively. When minority variants are taken into account, the prevalence of resistance to etravirine, darunavir and raltegravir at baseline was 29%, 40% and 9%, respectively. No difference was observed in the prevalence of MRVs between patients with virological failure and those with virological success, except a trend for patients exhibiting baseline etravirine MRVs (50% versus 26%, P = 0.09).
  
  
  CONCLUSIONS
  We have shown a high level of MRVs at baseline in highly pre-treated patients harbouring multiresistant viruses. However, these MRVs were not associated with an increased risk of virological failure, except for a trend for etravirine MRVs.
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France charlotte.charpentier@bch.aphp.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada University of British Columbia, Vancouver, BC, Canada.
authors.forename: Guinevere Q
authors.initials: GQ
authors.lastname: Lee
authors.affiliation: Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955 Team 18, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Visseaux
authors.affiliation: AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Storto
authors.affiliation: INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, F-33000 Bordeaux, France Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, F-33000 Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.affiliation: AP-HP, Hôpital Saint-Louis, Service de Maladies Infectieuses et Tropicales, INSERM U941, Université Paris Diderot, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: AP-HP, Hôpital de la Pitié-Salpétrière, Service de Maladies Infectieuses et Tropicales, F-75013 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat, Service de Maladies Infectieuses et Tropicales, F-75018 Paris, France.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada University of British Columbia, Vancouver, BC, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000069454:Darunavir / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008137:Longitudinal Studies; D009154:Mutation; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines; D000068898:Raltegravir Potassium / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D000068898:Raltegravir Potassium; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D000069454:Darunavir
keywords: HIV; quasispecies; ultra-deep sequencing