title: Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options.
abstract: BACKGROUND
  Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection.
  
  
  METHODS
  We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy.
  
  
  RESULTS
  Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%).
  
  
  CONCLUSIONS
  In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
authors.affiliation: Weill Cornell Medical College, New York, NY 10021, USA. imj2001@med.cornell.edu
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Gregory
authors.initials: G
authors.lastname: Everson
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: M Tarek
authors.initials: MT
authors.lastname: Al-Assi
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: Di
authors.initials: D
authors.lastname: An
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.forename: Diana
authors.initials: D
authors.lastname: Brainard
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Jordan
authors.initials: J
authors.lastname: Feld
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir