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

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.

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.

PMID:
25364884
PMCID:
PMC4586065
DOI:
10.7326/M14-1211
[Indexed for MEDLINE]
Free PMC Article

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