Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study

Ann Intern Med. 2014 Nov 4;161(9):634-8. doi: 10.7326/M14-1211.

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.

Design: Phase 2a, open-label study. (ClinicalTrials.gov: NCT01805882).

Setting: Single U.S site.

Patients: 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.

Measurements: 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.

Limitation: Small sample size.

Conclusion: 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.

Primary funding source: National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Cancer Institute, and Gilead Sciences.

Trial registration: ClinicalTrials.gov NCT00047385.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Drug Therapy, Combination
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use*
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • RNA, Viral / blood
  • Recurrence
  • Ribavirin / therapeutic use
  • Sofosbuvir
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • RNA, Viral
  • ledipasvir
  • Ribavirin
  • Uridine Monophosphate
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT00047385