title: Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study.
abstract: BACKGROUND
  Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (ATV) or raltegravir (RAL) pharmacokinetic parameters in a subgroup of patients.
  
  
  METHODS
  In this single-arm phase 2 trial, HIV-1/HCV-genotype-1-coinfected patients received PEGylated-interferonα2b (1.5 μg/kg/week)+ ribavirin (800-1400 mg/day) alone until W4 and with BOC(800 mgTID) until W48. Based on virologic response at W8, the three drugs were stopped or PEGylated-interferon/ribavirin was continued alone until W72. The primary endpoint was SVR at W24 off-therapy (SVR24).
  
  
  RESULTS
  64 patients were included. SVR24 was achieved in 53% of patients (CI90%: 43-63%) and in 90% of previous relapsers. In univariate analysis, SVR24 was associated with response to previous HCV treatment, HCV-1b subtype, HCV-RNA decline, ribavirin-Ctrough at W4, and HCV-RNA at W8 but not to fibrosis score, IL28B genotype, or boceprevir-Ctrough at W8. In multivariate analysis, SVR24 remained associated with response to previous HCV treatment [non-responders versus null responders: OR=5.0(1.3-20.0); relapsers vs. null responders: OR=28.8(4.9-169.5)]. HCV treatment was discontinued for adverse events in 17% of patients. A 51% decrease in ATV/r-AUC0-8 h (p<0.01) and a 57% increase in RAL-AUC0-8 h (p<0.01) were observed, although atazanavir/r or raltegravir did not affect BOC-AUC0-8 h significantly. The ATV mean Cthrough fell from 763.8 ng/mL (CI 95%: 230.3-1297.3) without BOC to 507.7 ng/mL (CI 95%: 164-851.4) with BOC.
  
  
  CONCLUSIONS
  Boceprevir-based regimen demonstrated a high SVR24 rate in treatment-experienced HIV-HCV genotype-1-coinfected relapsers.
authors.affiliation: a Aix-Marseille University, AP-HM Sainte-Marguerite, Service d'Immuno-Hématologie Clinique , Marseille , France.|b INSERM, UMR 912 (SESSTIM) , Marseille , France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.affiliation: c Rennes 1 University, Pontchaillou University Hospital, Service de Pharmacologie , Rennes , France.|d INSERM, CIC 1414 Clinical Investigation Centre , Rennes , France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
authors.affiliation: e Nice University, Pasteur University Hospital , Laboratoire de Pharmacologie et de Toxicologie Médicale , Nice , France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Garraffo
authors.affiliation: f Aix-Marseille University, AP-HM Timone, Fédération de Microbiologie Hospitalière , Marseille , France.|g URMITE , UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.affiliation: h Bourgogne University, Bocage University Hospital , Département d'Infectiologie , UMR 1347, Dijon , France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.affiliation: i Aix-Marseille University, AP-HM Timone, Service de Pharmacocinétique et Toxicologie , Marseille , France.|j INSERM , UMR 911 (CRO2), Marseille , France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.affiliation: c Rennes 1 University, Pontchaillou University Hospital, Service de Pharmacologie , Rennes , France.|d INSERM, CIC 1414 Clinical Investigation Centre , Rennes , France.
authors.forename: Alain
authors.initials: A
authors.lastname: Renault
authors.affiliation: k AP-HM Saint-Joseph, Service d'Hépato-Gastro-Entérologie , Marseille , France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: l European Hospital , Marseille , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.affiliation: m Paris Descartes University , PRES Sorbonne Paris-Cité, EA 7327, Paris , France.|n Paris-Sud University, AP-HP Bicêtre Hospital, Service de Médecine Interne , Le Kremlin-Bicêtre, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.affiliation: o Toulouse 3 University, Purpan University Hospital, Service de Médecine Interne , Toulouse , France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: p Nice University, Archet University Hospital, Service d'Infectiologie , Nice , France.
authors.forename: Alissa
authors.initials: A
authors.lastname: Naqvi
authors.affiliation: b INSERM, UMR 912 (SESSTIM) , Marseille , France.|q ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur , Marseille , France.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrieri
authors.affiliation: r Paris 7 - Denis Diderot University, AP-HP Saint-Louis Hospital, Service des Maladies Infectieuses et Tropicales , Paris , France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D060085:Coinfection / Q000188:drug therapy* / Q000821:virology; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a
keywords: Boceprevir; Direct-acting antiviral drug; HCV retreatment; HIV/HCV coinfection