title: Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities.
abstract: We conducted a phase 4, open-label study with limited exclusion criteria to evaluate the safety and efficacy of sofosbuvir and ribavirin in veterans with hepatitis C virus genotype 2 infection, and compensated cirrhosis. This population is often excluded from clinical studies.
  
  
  
  We performed a prospective study of treatment-naive (n = 47) and treatment-experienced (n = 19) patients with chronic hepatitis C virus genotype 2 infection and compensated cirrhosis at 15 Department of Veterans Affairs sites. All subjects were given sofosbuvir (400 mg, once daily) plus ribavirin (1000-1200 mg/day) in divided doses for 12 weeks. Patients with major psychiatric diseases or alcohol or substance use disorders were not excluded. The primary endpoint was sustained virologic response 12 weeks after therapy.
  
  
  
  Fifty-two patients achieved a sustained virologic response 12 weeks after therapy (79%; 95% confidence interval, 67%-88%); 16 of these patients were treatment experienced (84%; 95% confidence interval, 60%-97%) and 36 were treatment naive (77%; 95% confidence interval, 62%-88%). All patients had at least 1 comorbidity. Thirty-five percent had depression, 24% had posttraumatic stress disorder, and 30% had anxiety disorder. In addition, 29% had current substance use. Of the 7 patients (11%) who discontinued the study treatment prematurely, 3 did so because of adverse events. The most common adverse events were fatigue, anemia, nausea, and headache. Serious adverse events occurred in 8 patients. Only 2 of the serious adverse events (anemia and nausea) were considered to be related to study treatment.
  
  
  
  In a phase 4 study, 12 weeks treatment with sofosbuvir and ribavirin led to a sustained virologic response 12 weeks after therapy in almost 80% of veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities, regardless of their treatment history. ClinicalTrials.gov, Number: NCT02128542.
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, California. Electronic address: samuel.ho2@va.gov.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Ho
authors.affiliation: San Francisco Veterans Affairs Healthcare System, San Francisco, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Monto
authors.affiliation: Miami Veterans Affairs Healthcare System, Miami, Florida.
authors.forename: Adam
authors.initials: A
authors.lastname: Peyton
authors.affiliation: Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.
authors.forename: David E
authors.initials: DE
authors.lastname: Kaplan
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Sean
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Scott
authors.initials: S
authors.lastname: Moon
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Amanda
authors.initials: A
authors.lastname: Copans
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rossaro
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Anupma
authors.initials: A
authors.lastname: Roy
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hadley
authors.initials: H
authors.lastname: Le
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: William
authors.initials: W
authors.lastname: Guyer
authors.affiliation: Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Obaid
authors.initials: O
authors.lastname: Shaikh
authors.affiliation: Richmond Veterans Affairs Medical Center, Richmond, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Veterans Affairs Long Beach Healthcare System, Long Beach, California.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014728:Veterans
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: Clinical Trial; DAA; NS5B Inhibitor; Substance Abuse; VA