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Basic Characteristics of Mutations
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Mutation Site
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S282T |
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Mutation Site Sentence
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HCV RNA concentration and population sequencing to detect NS5B S282T mutations. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NS5B |
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Standardized Encoding Gene
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NS5B
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Genotype/Subtype
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1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Hepatitis C, Chronic
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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America |
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Literature Information
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PMID
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25364884
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Title
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Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study
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Author
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Osinusi A,Kohli A,Marti MM,Nelson A,Zhang X,Meissner EG,Silk R,Townsend K,Pang PS,Subramanian GM,McHutchison JG,Fauci AS,Masur H,Kottilil S
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Journal
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Annals of internal medicine
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Journal Info
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2014 Nov 4;161(9):634-8
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Abstract
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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.
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Sequence Data
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-
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