title: HIV-1 Coreceptor Usage Assessment by Ultra-Deep Pyrosequencing and Response to Maraviroc.
abstract: BACKGROUND
  Maraviroc is an HIV entry inhibitor that alters the conformation of CCR5 and is poorly efficient in patients infected by viruses that use CXCR4 as an entry coreceptor. The goal of this study was to assess the capacity of ultra-deep pyrosequencing (UDPS) and different data analysis approaches to characterize HIV tropism at baseline and predict the therapeutic outcome on maraviroc treatment.
  
  
  METHODS
  113 patients with detectable HIV-1 RNA on HAART were treated with maraviroc. The virological response was assessed at months 1, 3 and 6. The sequence of the HIV V3 loop was determined at baseline and prediction of maraviroc response by different software and interpretation algorithms was analyzed.
  
  
  RESULTS
  UDPS followed by analysis with the Pyrotrop software or geno2pheno algorithm provided better prediction of the response to maraviroc than Sanger sequencing. We also found that the H34Y/S substitution in the V3 loop was the strongest individual predictor of maraviroc response, stronger than substitutions at positions 11 or 25 classically used in interpretation algorithms.
  
  
  CONCLUSIONS
  UDPS is a powerful tool that can be used with confidence to predict maraviroc response in HIV-1-infected patients. Improvement of the predictive value of interpretation algorithms is possible and our results suggest that adding the H34S/Y substitution would substantially improve the performance of the 11/25/charge rule.
authors.affiliation: National Reference Center for Viral Hepatitis B, C and delta, Department of Virology; Henri Mondor Hospital, University of Paris-Est, Créteil, France; INSERM U955, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: Department of Virology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulié
authors.affiliation: Department of Virology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Department of Virology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Department of Virology, Bichat-Claude Bernard Hospital, HUPNVS, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Department of Virology, Bichat-Claude Bernard Hospital, HUPNVS, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.affiliation: INSERM U943 UPMC, UMR-S 943, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.affiliation: Department of Virology, University Hospital of Bordeaux and UMR5234, University of Bordeaux, Bordeaux, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Recordon-Pinson
authors.affiliation: Department of Virology, University Hospital of Bordeaux and UMR5234, University of Bordeaux, Bordeaux, France.
authors.forename: Pantxika
authors.initials: P
authors.lastname: Bellecave
authors.affiliation: National Reference Center for Viral Hepatitis B, C and delta, Department of Virology; Henri Mondor Hospital, University of Paris-Est, Créteil, France; INSERM U955, Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: Department of Virology, University Hospital of Bordeaux and UMR5234, University of Bordeaux, Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
mesh_terms: D000328:Adult; D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry; D012367:RNA, Viral / Q000032:analysis; D012372:ROC Curve; D017423:Sequence Analysis, RNA; D012984:Software; D014230:Triazoles / Q000627:therapeutic use*; D056189:Viral Tropism
chemical_list: D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc