title: Phase 3 trial of first generation protease inhibitor therapy for hepatitis C virus/human immunodeficiency virus coinfection.
abstract: OBJECTIVE
  To evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial.
  
  
  METHODS
  A prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR).
  
  
  RESULTS
  A total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA < lower limit of quantification, target not detected, target not detected) were 35.6% in TN and 30.3% in TE. Response rates at SVR24 were 28% in TN and 10% in TE, and exceeded those in historical controls. The highest rate was observed in TN non-cirrhotic participants (36.8% and the lowest in TE cirrhotics (26.3%). Cirrhotic TN participants had a 27.8% SVR12 rate and 32.1% of TE non-cirrhotics achieved SVR12. Significantly lower response rates were observed among black participants; in the TE, SVR12 was 39.7% in white participants but only 13.2% of black subjects (P= 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P= 0.09).
  
  
  CONCLUSIONS
  The trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Minhee
authors.initials: M
authors.lastname: Kang
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Sterling
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Triin
authors.initials: T
authors.lastname: Umbleja
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Marks
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Kiser
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Beverly
authors.initials: B
authors.lastname: Alston-Smith
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Wayne
authors.initials: W
authors.lastname: Greaves
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.forename: Adeel A
authors.initials: AA
authors.lastname: Butt
authors.affiliation: Kenneth E Sherman, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors.lastname: The Actg Birth Study Team
keywords: Boceprevir; Hepatitis C virus; Human immunodeficiency virus; Pegylated interferon alfa; Ribavirin