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

Anu Osinusi, Anita Kohli, Miriam M. Marti, Amy Nelson, Xiaozhen Zhang, Eric G. Meissner, Rachel Silk, Kerry Townsend, Phillip S. Pang, G. Mani Subramanian, John G. McHutchison, Anthony S. Fauci, Henry Masur, Shyam Kottilil

Research output: Contribution to journalArticlepeer-review

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 welltolerated 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.

Original languageEnglish (US)
Pages (from-to)634-638
Number of pages5
JournalAnnals of internal medicine
Volume161
Issue number9
DOIs
StatePublished - Nov 4 2014

ASJC Scopus subject areas

  • Internal Medicine

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