title: Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial.
abstract: BACKGROUND
  Rates of sustained virological response (SVR) to peginterferon-ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone.
  
  
  METHODS
  In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18-65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 μg/kg per week with weight-based ribavirin (600-1400 mg per day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699.
  
  
  RESULTS
  From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7-52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon-ribavirin and four controls had HIV virological breakthrough.
  
  
  CONCLUSIONS
  Boceprevir in combination with peginterferon-ribavirin could be an important therapeutic option for patients with HCV and HIV.
  
  
  BACKGROUND
  Merck.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: msulkowski@jhmi.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
authors.affiliation: Université Paris Descartes, Inserm U-1016, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Hospital Clinic-University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Mallolas
authors.affiliation: Muñiz Hospital, Buenos Aires, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fainboim
authors.affiliation: University of Ottawa, Ottawa, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Saint Michael's Medical Center, Newark, NJ, USA.
authors.forename: Jihad
authors.initials: J
authors.lastname: Slim
authors.affiliation: University Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mak
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Thompson
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Anita Ym
authors.initials: AY
authors.lastname: Howe
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenning
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sklar
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA. Electronic address: wayne.greaves@merck.com.
authors.forename: Wayne
authors.initials: W
authors.lastname: Greaves
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010919:Placebos; D012367:RNA, Viral; 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; C417083:peginterferon alfa-2b