title: Sofosbuvir and ribavirin in HCV genotypes 2 and 3.
abstract: BACKGROUND
  In clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection.
  
  
  METHODS
  We conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4:1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
  
  
  RESULTS
  Of the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus.
  
  
  CONCLUSIONS
  Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).
authors.affiliation: From the Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany (S.Z.); Royal Free Hospital and University College London School of Medicine, London (G.M.D.); Tartu University Hospital, Tartu, Estonia (R.S.); Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy (A.M.); Medical University of Bialystok, Bialystok, Poland (R.F.); Gilead Sciences, Foster City, CA (R.H.H., A.I., E.S., D.M.B., W.T.S., G.M.S., J.G.M.); Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm (O.W.); Academic Medical Center, Amsterdam (H.W.R.); Medical University of Vienna, Vienna (P.F.); Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, INSERM Unité 955, Créteil, France (C.H.); and Hospital Universitario Val d'Hebron, Barcelona (R.E.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Dusheiko
authors.forename: Riina
authors.initials: R
authors.lastname: Salupere
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Robert H
authors.initials: RH
authors.lastname: Hyland
authors.forename: Ari
authors.initials: A
authors.lastname: Illeperuma
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.forename: Hendrik W
authors.initials: HW
authors.lastname: Reesink
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir