title: Sofosbuvir and ribavirin for 6 weeks is not effective among people with recent hepatitis C virus infection: The DARE-C II study.
abstract: While interferon-based therapy has excellent efficacy in acute and recent hepatitis C virus (HCV) infection, the side effect profile limits implementation. Sofosbuvir and ribavirin for 12-24 weeks is safe and well tolerated in chronic HCV, with efficacy dependent on genotype and disease stage. The aim of this study was to assess the efficacy of sofosbuvir and ribavirin for 6 weeks in individuals with recent HCV infection. In this open-label study conducted in Australia and New Zealand, adults with recent HCV (duration of infection <12 months) received sofosbuvir 400 mg daily and weight-based ribavirin (<75 kg, 1,000 mg/day; ≥75 kg, 1,200 mg/day) for 6 weeks. The primary efficacy endpoint was sustained virological response at posttreatment week 12 (SVR12). Nineteen participants commenced sofosbuvir and ribavirin (89% male, 74% with human immunodeficiency virus, 68% genotype 1a). Four (21%) reported a symptomatic HCV seroconversion illness, including 2 with jaundice. At baseline, median HCV RNA was 5.4 log10IU/mL (interquartile range 4.4-6.8) and median estimated duration of infection was 37 weeks (interquartile range 27-41). At the end of treatment, HCV RNA was nonquantifiable in 89% (n = 17). SVR4 and SVR12 were 42% (n = 8) and 32% (n = 6), respectively. Treatment failure was due to nonresponse (n = 2), posttreatment relapse (n = 9), reinfection (n = 1), and loss to follow-up (n = 1). The regimen was well tolerated with minimal hematological toxicity. SVR12 was related to baseline HCV RNA (≤6 log10IU/mL, P = 0.018) and early on-treatment viral kinetics (HCV RNA below the level of quantitation at week 1, P = 0.003).
  
  
  
  Six weeks of sofosbuvir and ribavirin was safe and well tolerated, but efficacy was suboptimal; further research is needed to determine whether more potent interferon-free direct-acting antiviral regimens will allow treatment duration to be shortened in recent, predominantly asymptomatic HCV infection. (Hepatology 2016;64:1911-1921).
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Martinello
authors.affiliation: Auckland Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.affiliation: Burnet Institute, Melbourne, VIC, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.affiliation: The Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Joe
authors.initials: J
authors.lastname: Sasadeusz
authors.affiliation: Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Shaw
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Petoumenos
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Applegate
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Maire
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Philippa
authors.initials: P
authors.lastname: Marks
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir