title: Virological failure of patients on maraviroc-based antiretroviral therapy.
abstract: OBJECTIVE
  Virological failure (VF) in patients on maraviroc-based treatment has been associated with altered HIV tropism and resistance to maraviroc. This multicentre study aimed to characterize VF in patients treated with maraviroc.
  
  
  METHODS
  We analysed 27 patients whose treatment failed between 2008 and 2011. They had been screened for HIV tropism before maraviroc initiation using population-based V3 genotyping. HIV-1 tropism and resistance of R5 viruses to maraviroc at VF and at baseline were determined retrospectively using an ultrasensitive recombinant virus assay (RVA).
  
  
  RESULTS
  Viruses from 27 patients given maraviroc on the basis of the R5 genotype were characterized at the time of treatment failure. The RVA indicated that 12 patients harboured CXCR4-using viruses and 15 (56%) had pure R5 viruses at failure. One-third of those harbouring CXCR4-using viruses (4/12) were infected with R5X4/X4 viruses according to the RVA before maraviroc initiation. We analysed the phenotypic resistance to maraviroc of four patients harbouring R5 viruses at failure; two harboured viruses whose maximum percentage inhibition was reduced by 65%-90%, while the other two were infected with susceptible viruses. All patients had effective concentrations of drugs.
  
  
  CONCLUSIONS
  Half of the maraviroc-treated patients who experienced VF harboured CXCR4-using viruses at failure, one-third of them were detected by a phenotypic method before maraviroc initiation. Phenotypic assessment of R5 virus resistance to CCR5 antagonists at failure could help optimize antiretroviral therapy.
authors.affiliation: INSERM, U1043, Toulouse F-31300, France Université de Toulouse, Université Paul Sabatier, CPTP, Toulouse, France raymond.s@chu-toulouse.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Raymond
authors.affiliation: Laboratoire de Virologie Hôpital Pontchaillou, Rennes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Maillard
authors.affiliation: Laboratoire de Virologie Hôpital Tenon, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Amiel
authors.affiliation: Laboratoire de Pharmacologie Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: Laboratoire de Virologie Hôpital de la Croix Rousse, Lyon, France.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Trabaud
authors.affiliation: Laboratoire de Virologie Hôpital Paul Brousse, Villejuif, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Desbois
authors.affiliation: Laboratoire de Virologie, CHU de Bordeaux, France.
authors.forename: Pantxika
authors.initials: P
authors.lastname: Bellecave
authors.affiliation: Laboratoire de Virologie Hôpital Saint Louis, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris F-75013, France.
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulie
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013 Paris, France AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris F-75013, France.
authors.forename: Anne Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Laboratoire de Virologie Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.affiliation: INSERM, U1043, Toulouse F-31300, France Université de Toulouse, Université Paul Sabatier, CPTP, Toulouse, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D003510:Cyclohexanes / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load; D056189:Viral Tropism
chemical_list: D044966:Anti-Retroviral Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc
keywords: CXCR4; HIV-1 tropism determination; entry; phenotypic assay; resistance to maraviroc