title: Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial.
abstract: BACKGROUND
  Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population.
  
  
  METHODS
  HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24).
  
  
  RESULTS
  Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed.
  
  
  CONCLUSIONS
  Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cotte
authors.forename: Joséphine
authors.initials: J
authors.lastname: Braun
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.forename: Corine
authors.initials: C
authors.lastname: Vincent
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Hugues
authors.initials: H
authors.lastname: Aumaitre
authors.forename: Dominique
authors.initials: D
authors.lastname: Batisse
authors.forename: Pierre
authors.initials: P
authors.lastname: de Truchis
authors.forename: Anne
authors.initials: A
authors.lastname: Gervais
authors.forename: Christian
authors.initials: C
authors.lastname: Michelet
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittecoq
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rosa
authors.forename: Inga
authors.initials: I
authors.lastname: Bertucci
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chevaliez
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a
keywords: HCV retreatment; HIV/HCV coinfection; direct acting agent; telaprevir