title: Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial.
abstract: BACKGROUND
  Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown.
  
  
  OBJECTIVE
  To assess the safety and efficacy of TVR plus PEG-IFN-α2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration.
  
  
  METHODS
  Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853).
  
  
  METHODS
  16 international multicenter sites.
  
  
  METHODS
  62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a-ribavirin or placebo plus PEG-IFN-α2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a-ribavirin.
  
  
  METHODS
  HCV RNA concentrations.
  
  
  RESULTS
  Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a-ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR.
  
  
  CONCLUSIONS
  Small sample size and appreciable dropout rate.
  
  
  CONCLUSIONS
  In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.
authors.affiliation: Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Baltimore, MD 21287, USA. msulkowski@jhmi.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Dieterich
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bsharat
authors.forename: Lisa
authors.initials: L
authors.lastname: Mahnke
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Shahin
authors.initials: S
authors.lastname: Gharakhanian
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
authors.forename: Joshua
authors.initials: J
authors.lastname: Henshaw
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Bambang
authors.initials: B
authors.lastname: Adiwijaya
authors.forename: Varun
authors.initials: V
authors.lastname: Garg
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Rubin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Adda
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a