title: Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial).
abstract: OBJECTIVE
  ROCnRAL ANRS-157 was a single-arm study designed to evaluate a switch to a maraviroc (300 mg twice a day) plus raltegravir (400 mg twice a day) regimen in virologically suppressed HIV-1-infected patients (ClinicalTrials.gov: NCT01420523). The aim of this work was to investigate the factors associated with virological failure (VF) (5/44 patients) or virological rebound defined as one viral load (VL) >50 copies/mL or VL >1 copy/mL.
  
  
  METHODS
  At baseline (BL), ultradeep sequencing (UDS) of DNA gp120 V3 and integrase regions and quantification of HIV DNA were performed in PBMCs. Tropism, VL, BL ultrasensitive HIV RNA VL, BL HIV DNA VL, subtype, age, ethnicity, transmission group, AIDS status, nadir CD4 and BL CD4 cell count, time since HIV diagnosis, duration of ART and suppressed viraemia, VL zenith, CD4/CD8 ratio and BL CD8 cell count were investigated as potential factors associated with virological rebound.
  
  
  RESULTS
  The proportion of patients with VL <1 copy/mL did not evolve over time. Among the 44 included patients, 3 had minority X4-tropic viruses determined by UDS at BL and one of them presented VF. Minority resistant variants in the integrase gene were detected at BL at two positions (E138 and G140) for three patients who did not have VF. Among all studied factors, none was associated with virological rebound.
  
  
  CONCLUSIONS
  Maraviroc plus raltegravir failed to maintain virological suppression in virologically suppressed HIV-1-infected patients. However, neither minority viral variants nor ultrasensitive viraemia was found to be a predictive factor of VF or virological rebound in this context.
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris F-75013, France cathia.soulie@psl.aphp.fr.
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulié
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France.
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.affiliation: National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Darty
authors.affiliation: National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rodriguez
authors.affiliation: National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Donati
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris F-75013, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sayon
authors.affiliation: IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, INSERM, F-75018 Paris, France AP-HP, Hôpital Bichat, Laboratoire de Pharmacologie, F-75018 Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Service de maladies infectieuses, F-75013 Paris, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Service de maladies infectieuses, F-75013 Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Caby
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Service de maladies infectieuses, F-75013 Paris, France.
authors.forename: Luminita
authors.initials: L
authors.lastname: Schneider
authors.affiliation: AP-HP, Hôpital Kremlin-Bicêtre, Service de maladies infectieuses, F-94270 Kremlin-Bicêtre, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Canestri
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Service de maladies infectieuses, F-75013 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris F-75013, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris F-75013, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D000077592:Maraviroc; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D012307:Risk Factors; D017211:Treatment Failure; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc