title: Sofosbuvir for previously untreated chronic hepatitis C infection.
abstract: BACKGROUND
  In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.
  
  
  METHODS
  We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy.
  
  
  RESULTS
  In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon.
  
  
  CONCLUSIONS
  In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.).
authors.affiliation: Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX 78215, USA. lawitz@txliver.com
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: David
authors.initials: D
authors.lastname: Wyles
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.forename: Michael
authors.initials: M
authors.lastname: Schultz
authors.forename: Mitchell N
authors.initials: MN
authors.lastname: Davis
authors.forename: Zeid
authors.initials: Z
authors.lastname: Kayali
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Lisa
authors.initials: L
authors.lastname: Nyberg
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: Robert H
authors.initials: RH
authors.lastname: Hyland
authors.forename: Sarah
authors.initials: S
authors.lastname: Arterburn
authors.forename: Deyuan
authors.initials: D
authors.lastname: Jiang
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: Aasim M
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
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; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014542:Uridine Monophosphate; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir