title: Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial.
abstract: BACKGROUND
  Effective treatment options are needed for patients with genotype 1 or 3 hepatitis C virus (HCV) infection in whom previous therapy has failed.
  
  
  OBJECTIVE
  To assess the efficacy and safety of sofosbuvir plus velpatasvir, with and without ribavirin, in treatment-experienced patients.
  
  
  METHODS
  Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01909804).
  
  
  METHODS
  58 sites in Australia, New Zealand, and the United States.
  
  
  METHODS
  Treatment-experienced adults with genotype 3 HCV infection without cirrhosis (cohort 1) and with compensated cirrhosis (cohort 2) and patients with genotype 1 HCV infection that was unsuccessfully treated with a protease inhibitor with peginterferon and ribavirin (50% could have compensated cirrhosis) (cohort 3).
  
  
  METHODS
  All patients received 12 weeks of treatment that included 400 mg of sofosbuvir once daily. Patients in each cohort were randomly assigned to 25 mg of velpatasvir once daily with or without ribavirin or 100 mg of velpatasvir once daily with or without ribavirin.
  
  
  METHODS
  Proportion of patients with sustained virologic response at week 12 after treatment (SVR12).
  
  
  RESULTS
  In cohort 1, SVR12 rates were 85% with 25 mg of velpatasvir, 96% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 100% with 100 mg of velpatasvir plus ribavirin. In cohort 2, SVR12 rates were 58% with 25 mg of velpatasvir, 84% with 25 mg of velpatasvir plus ribavirin, 88% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. In cohort 3, SVR12 rates were 100% with 25 mg of velpatasvir, 97% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. The most common adverse events were headache, fatigue, and nausea.
  
  
  CONCLUSIONS
  Treatment assignments were not blinded, and no inferential statistics were planned.
  
  
  CONCLUSIONS
  Treatment with 400 mg of sofosbuvir plus 100 mg of velpatasvir for 12 weeks was well-tolerated and highly effective in treatment-experienced patients with genotype 1 or 3 HCV infection.
  
  
  BACKGROUND
  Gilead Sciences.
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.forename: Steven L
authors.initials: SL
authors.lastname: Flamm
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Sonal
authors.initials: S
authors.lastname: Kumar
authors.forename: Simone I
authors.initials: SI
authors.lastname: Strasser
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: Lingling
authors.initials: L
authors.lastname: Han
authors.forename: Brian
authors.initials: B
authors.lastname: Doehle
authors.forename: Erik
authors.initials: E
authors.lastname: Mogalian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Mordechai
authors.initials: M
authors.lastname: Rabinovitz
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.forename: Catherine A M
authors.initials: CA
authors.lastname: Stedman
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D006576:Heterocyclic Compounds, 4 or More Rings; D012367:RNA, Viral; D012254:Ribavirin; D000069474:Sofosbuvir; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans