title: Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection.
abstract: OBJECTIVE
  We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection.
  
  
  METHODS
  The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (sustained virologic response [SVR12]). From October 2013 until April 2014, we enrolled and treated 592 patients-48 with genotype 2 HCV and compensated cirrhosis who had not achieved SVR with previous treatments and 544 with genotype 3 HCV (279 treatment-naïve and 265 previously treated). Overall, 219 patients (37%) had compensated cirrhosis. The last post-treatment week 12 patient visit was in January 2015.
  
  
  RESULTS
  Rates of SVR12 among patients with genotype 2 HCV were 87% and 100%, for those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 94% for those receiving sofosbuvir, peginterferon, and ribavirin for 12 weeks. Rates of SVR12 among patients with genotype 3 HCV were 71% and 84% in those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 93% in those receiving sofosbuvir, peginterferon, and ribavirin. On-treatment virologic failure occurred in 3 patients with HCV genotype 3a receiving sofosbuvir and ribavirin for 24 weeks. The most common adverse events were fatigue, headache, insomnia, and nausea. Overall, 1% of patients discontinued treatment due to adverse events.
  
  
  CONCLUSIONS
  Among patients with genotype 3 HCV infection, including a large proportion of treatment-experienced patients with cirrhosis, the combination of sofosbuvir, peginterferon, and ribavirin for 12 weeks produces high rates of SVR. Treatment-experienced patients with cirrhosis and genotype 2 HCV infection had high rates of SVR in all groups. EudraCT ID 2013-002641-11.
authors.affiliation: Queen Mary University of London, Barts Health, United Kingdom. Electronic address: g.r.foster@qmul.ac.uk.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Monash Health and Monash University, Melbourne, Victoria, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.affiliation: Imperial College Healthcare, National Health Service Trust, London, United Kingdom.
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.affiliation: St George's University of London, London, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Forton
authors.affiliation: ID Care, Hillsborough, New Jersey.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Nahass
authors.affiliation: Storr Liver Centre, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Nuffield Department of Medicine, Oxford NHIR BRC and representing STOP-HCV, United Kingdom.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, United Kingdom.
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000145:classification / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000187:drug effects; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: BOSON; Hepatitis C Virus; Nucleotide Analog; Peginterferon