HCV Mutation Detail Information

Virus Mutation HCV Mutation A156T


Basic Characteristics of Mutations
Mutation Site A156T
Mutation Site Sentence A156T or A156V were the most prevalent emergent NS3 RAS in patients with GT1a or GT1b infection, but were not observed in patients with GT3 infection.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NS3
Standardized Encoding Gene NS3
Genotype/Subtype 1a;1b
Viral Reference AJ238799;NC_004102
Functional Impact and Mechanisms
Disease HCV Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment VOX
Location -
Literature Information
PMID 29063860
Title Characterization of HCV resistance from a 3-day monotherapy study of voxilaprevir, a novel pangenotypic NS3/4A protease inhibitor
Author Lawitz E,Yang JC,Stamm LM,Taylor JG,Cheng G,Brainard DM,Miller MD,Mo H,Dvory-Sobol H
Journal Antiviral therapy
Journal Info 2018;23(4):325-334
Abstract BACKGROUND: Voxilaprevir (VOX; GS-9857) is a pangenotypic HCV NS3/4A protease inhibitor (PI) with potent antiviral activity against HCV genotypes (GTs) 1-6 and improved coverage of GT1 NS3 resistance-associated substitutions (RAS) associated with other HCV PIs. In a 3-day Phase Ib monotherapy study in patients infected with HCV GT1a, 1b, 2, 3 and 4, VOX was well-tolerated and resulted in maximal mean viral load reduction >3 log(10) IU/ml at the 100 mg dose across all genotypes evaluated. This report characterizes the HCV NS3 RAS in the study. METHODS: The NS3 gene was amplified and successfully deep sequenced using MiSeq for 66 patients at baseline and 61 patients post-baseline using 15% and 1% assay cutoffs. RESULTS: With a 15% assay cutoff, pretreatment HCV NS3 RAS were present in the HCV of 38% (9/24) of patients with GT1a and 5% (1/19) with GT3a; there were no pretreatment NS3 RAS present in patients with GT1b (n=6), GT2 (n=7) or GT4 (n=4). In patients with and without pretreatment NS3 RAS, >/=3.4 log(10) mean maximal viral load reductions over 3 days of VOX administration were observed. The majority of patients did not have detectable treatment-emergent NS3 RAS and only 12% (7/53) and 26% (14/53) had emergent NS3 RAS using 15% and 1% cutoffs, respectively. No NS3 RAS were detected in patients with GT2 or GT4. A156T or A156V were the most prevalent emergent NS3 RAS in patients with GT1a or GT1b infection, but were not observed in patients with GT3 infection. CONCLUSIONS: The lack of selection of NS3 RAS in the majority of patients demonstrates a high resistance barrier for VOX. ClinicalTrails.gov identifier NCT02185794.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.