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Basic Characteristics of Mutations
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Mutation Site
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V36M+R155K |
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Mutation Site Sentence
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The combination of V36M and R155K, known to confer high level of PI resistance, was present in patients 4, 5 and 6 post-treatment. |
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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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Protease |
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Standardized Encoding Gene
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NS3
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Genotype/Subtype
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1a |
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Viral Reference
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AF011751;AF054250
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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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IFNL3
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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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PI |
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Location
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Denmark |
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Literature Information
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PMID
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25438153
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Title
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Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in Denmark: identification of viral resistance mutations
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Author
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Solund C,Krarup H,Ramirez S,Thielsen P,Roge BT,Lunding S,Barfod TS,Madsen LG,Tarp B,Christensen PB,Gerstoft J,Laursen AL,Bukh J,Weis N
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Journal
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PloS one
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Journal Info
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2014 Dec 1;9(12):e113034
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Abstract
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BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.
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Sequence Data
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-
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