title: Sofosbuvir plus pegylated interferon and ribavirin in patients with genotype 1 hepatitis C virus in whom previous therapy with direct-acting antivirals has failed.
abstract: Retreatment of patients who have not achieved sustained virological response (SVR) after treatment with investigational direct-acting antiviral agents (DAAs) has not been extensively studied. We conducted an open-label trial to assess the efficacy and safety of sofosbuvir (SOF) plus pegylated interferon (Peg-IFN) and ribavirin (RBV) in patients with genotype 1 hepatitis C virus (HCV) who participated in previous studies of one or more Gilead investigational DAAs in combination with RBV with or without Peg-IFN. We enrolled 80 patients at 40 sites. All patients received SOF 400 mg once daily plus Peg-IFN-α 180 μg/week and weight-based ribavirin (1,000 or 1,200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 80 patients enrolled, 36 (45%) had received two or more courses of earlier treatment for HCV and 74 (93%) had at least one resistance-associated variant (RAV) at baseline. SVR12 was achieved by 63 of the 80 patients (79%) treated. Rates of SVR12 were similar across patient subgroups. Presence of RAVs at baseline did not appear to be associated with treatment failure. Seventy-one of eighty patients (89%) experienced at least one adverse event (AE), but most events were mild to moderate in severity. The most common AEs were fatigue, headache, and nausea. No patients discontinued all treatment because of AEs.
  
  
  CONCLUSIONS
  These findings suggest that SOF plus Peg-IFN and RBV for 12 weeks is effective and safe in patients who have not achieved SVR with earlier regimens of one or more DAAs plus Peg-IFN and RBV.
authors.affiliation: Université Paris Descartes, Hôpital Cochin, Inserm UMS20, Institut Pasteur, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: John Hopkins University, Baltimore, MD.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Southern California Liver Center, Coronado, CA.
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.affiliation: Aukland City Hospital, Auckland, NZ.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Brian
authors.initials: B
authors.lastname: Doehle
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Bittoo
authors.initials: B
authors.lastname: Kanwar
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Diana
authors.initials: D
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Infectious Disease Care, Hillsborough, NJ.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Nahass
authors.affiliation: Medical Associates Research Group, San Diego, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Weill Cornell Medical College, New York, NY.
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir; D017211:Treatment Failure; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir