• 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, and Shyam Kottilil.
• Ann. Intern. Med. 2014 Nov 4; 161 (9): 634638634-8.

BackgroundThe 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.ObjectiveTo assess the safety and efficacy of sofosbuvir plus ledipasvir in patients with chronic HCV GT-1 that relapsed after sofosbuvir plus ribavirin therapy.DesignPhase 2a, open-label study. (ClinicalTrials.gov: NCT01805882).SettingSingle U.S site.Patients14 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.MeasurementsHCV RNA concentration and population sequencing to detect NS5B S282T mutations.ResultsAll 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.LimitationSmall sample size.ConclusionThe 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 SourceNational Institute of Allergy and Infectious Diseases, National Institutes of Health, National Cancer Institute, and Gilead Sciences.

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