title: Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study.
abstract: BACKGROUND
  The interferon (IFN)-free regimen of sofosbuvir and ribavirin for 24 weeks was recently approved to treat chronic hepatitis C virus (HCV) genotype 1 (GT-1) infection for patients ineligible for IFN. However, sofosbuvir plus ribavirin therapy is associated with relapse in 15% to 30% of patients with HCV GT-1. Neither the mechanism of relapse nor the optimal re-treatment strategy for these patients is defined.
  
  
  OBJECTIVE
  To assess the safety and efficacy of sofosbuvir plus ledipasvir in patients with chronic HCV GT-1 that relapsed after sofosbuvir plus ribavirin therapy.
  
  
  METHODS
  Phase 2a, open-label study. (ClinicalTrials.gov: NCT01805882).
  
  
  METHODS
  Single U.S site.
  
  
  METHODS
  14 patients with HCV GT-1 that relapsed after treatment with sofosbuvir plus ribavirin for 24 weeks were re-treated with sofosbuvir plus ledipasvir for 12 weeks.
  
  
  METHODS
  HCV RNA concentration and population sequencing to detect NS5B S282T mutations.
  
  
  RESULTS
  All 14 patients treated with sofosbuvir plus ledipasvir for 12 weeks achieved a sustained virologic response, including 7 with advanced liver disease (Knodell Histology Activity Index score of 3 or 4) and 1 with a detectable NS5B S282T mutation after sofosbuvir plus ribavirin therapy. Sofosbuvir plus ledipasvir was well-tolerated with few adverse events. Four grade 3 events (elevated serum creatinine in a patient with baseline renal insufficiency, hypercholesterolemia, and hypophosphatemia) occurred. There were no grade 4 events or treatment discontinuations.
  
  
  CONCLUSIONS
  Small sample size.
  
  
  CONCLUSIONS
  The fixed-dose combination of sofosbuvir plus ledipasvir was efficacious in a small cohort of patients with HCV GT-1 that relapsed after sofosbuvir plus ribavirin therapy, even in the setting of advanced liver disease. Larger studies are needed to confirm these preliminary efficacy results.
  
  
  BACKGROUND
  National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Cancer Institute, and Gilead Sciences.
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Marti
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Zhang
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.forename: Rachel
authors.initials: R
authors.lastname: Silk
authors.forename: Kerry
authors.initials: K
authors.lastname: Townsend
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir