title: Efficacy of Ledipasvir Plus Sofosbuvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2 Infection.
abstract: Patients with chronic hepatitis C virus (HCV) genotype 2 have high rates of response to treatment with sofosbuvir and ribavirin. However, ribavirin is associated with hemolytic events and is poorly tolerated by some patients. We evaluated the effectiveness of sofosbuvir and ledipasvir in treatment-naïve and treatment-experienced patients with HCV genotype 2, comparing 12 versus 8 weeks of treatment.
  
  
  
  This Phase 2, open-label study included 2 cohorts in New Zealand. The first received a fixed-dose combination tablet of ledipasvir-sofosbuvir (90/400 mg) once daily for 12 weeks. If this cohort had a 90% rate of sustained virologic response (SVR) 4 weeks after treatment, a second cohort receiving 8 weeks of ledipasvir-sofosbuvir was to be enrolled. The primary endpoint in both cohorts was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after therapy (SVR12).
  
  
  
  SVR12 rates were 96% (25/26; 95% CI, 80%-100%) for 12 weeks and 74% (20/27; 95% CI, 54%-89%) for 8 weeks of ledipasvir-sofosbuvir. The single patient receiving 12 weeks of ledipasvir-sofosbuvir who did not reach SVR12 did not complete treatment because of withdrawing consent after receiving 1 dose of study drug. Six of the 7 patients who did not reach SVR12 after 8 weeks of treatment experienced virologic relapse after stopping therapy. The most common adverse events were headache (26% of patients), fatigue (21%), and nausea (17%). No patients discontinued treatment because of an adverse event.
  
  
  
  For treatment-naïve and -experienced patients, ledipasvir-sofosbuvir for 12 weeks is highly effective for the treatment of HCV genotype 2 (ClinicalTrials.gov: NCT02202980).
authors.affiliation: Liver Transplant Unit, Auckland City Hospital and University of Auckland, Auckland, New Zealand. Electronic address: edgane@adhb.govt.nz.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Hyland
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Stamm
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Inc, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Department of Gastroenterology, Christchurch Hospital and University of Otago, Christchurch, New Zealand.
authors.forename: Catherine A M
authors.initials: CAM
authors.lastname: Stedman
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D006261:Headache / Q000139:chemically induced; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000072230:Sustained Virologic Response
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir
keywords: Antiviral agents; Direct-acting antivirals; NS5A inhibitor; Polymerase inhibitor