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Basic Characteristics of Mutations
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Mutation Site
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I64M |
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Mutation Site Sentence
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A number of other amino acid changes from baseline were identified in patients who experienced vBT in the T or TPR group, including: V18I/V, T63I/T, I64I/M, A95A/T/V and P129A (G4a). |
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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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Standardized Encoding Gene
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Genotype/Subtype
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4 |
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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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HCV Infection
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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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- |
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Treatment
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- |
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Location
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France |
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Literature Information
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PMID
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24886541
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Title
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Virologic characterization of genotype 4 hepatitis C virus variants in patients treated with telaprevir
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Author
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De Meyer S,Ghys A,Dierynck I,Beumont M,Luo D,Picchio G
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Journal
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Virology journal
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Journal Info
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2014 May 16;11:93
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Abstract
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BACKGROUND: Study C210 was a Phase IIa, exploratory trial to assess the activity of telaprevir on hepatitis C virus (HCV) early viral kinetics in treatment-naive patients infected with genotype 4 (G4) HCV. METHODS: Patients were randomized to receive peginterferon and ribavirin alone, telaprevir monotherapy (T arm), or telaprevir in combination with peginterferon/ribavirin (TPR arm) for 15 days, followed by a 46- or 48-week standard treatment phase. The current analysis aimed to characterize the genotype and phenotype of HCV G4 variants emerging during telaprevir treatment. RESULTS: Five of the 8 (62.5%) patients in the telaprevir (T) arm had viral breakthrough (vBT) during the investigational treatment phase (between baseline and Day 15), compared to no patients in the TPR arm. HCV G4 viral variants with a T54A/T mutation were detected in two of these patients, as well as two other patients with detectable HCV RNA at the end of telaprevir treatment. Emergence of the T54A/T mutation was associated with a 2- to 4-fold decreased susceptibility to telaprevir. All patients with vBT during the investigational treatment phase or with a T54A/T mutation achieved undetectable HCV RNA 12 or 24 weeks after end of treatment with subsequent peginterferon/ribavirin treatment. CONCLUSIONS: In this analysis in G4 HCV-infected patients, more patients in the telaprevir monotherapy arm experienced vBT with resistant variants compared to none with telaprevir combination therapy. The most commonly selected mutation T54A in telaprevir-treated G4 HCV patients was previously described in the context of G1 infection. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (NCT00580801).
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Sequence Data
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-
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