HCV Mutation Detail Information

Virus Mutation HCV Mutation R155K


Basic Characteristics of Mutations
Mutation Site R155K
Mutation Site Sentence VL breakthroughs (>=1 log(10) from nadir) were seen in most patients on monotherapy and were caused by NS3/4A variants (R155K, D168V) conferring in vitro resistance to BI201335.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NS3-4A
Standardized Encoding Gene NS3-4A
Genotype/Subtype 1
Viral Reference -
Functional Impact and Mechanisms
Disease HCV Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment -
Location -
Literature Information
PMID 21145839
Title Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection
Author Manns MP,Bourliere M,Benhamou Y,Pol S,Bonacini M,Trepo C,Wright D,Berg T,Calleja JL,White PW,Stern JO,Steinmann G,Yong CL,Kukolj G,Scherer J,Boecher WO
Journal Journal of hepatology
Journal Info 2011 Jun;54(6):1114-22
Abstract BACKGROUND & AIMS: BI201335 is a highly specific and potent HCV protease inhibitor. This multiple rising dose trial evaluated antiviral activity and safety in chronic HCV genotype-1 patients. METHODS: Thirty-four treatment-naive patients were randomized to monotherapy with placebo or BI201335 at 20-240 mg once-daily for 14 days, followed by combination with pegylated interferon alfa/ribavirin (PegIFN/RBV) through Day 28. Nineteen treatment-experienced patients received 48-240 mg BI201335 once-daily with PegIFN/RBV for 28 days. HCV-RNA was measured with Roche COBAS TaqMan. RESULTS: In treatment-naive patients, median maximal viral load (VL) reductions during 14-day monotherapy were -3.0, -3.6, -3.7, and -4.2 log(10) for the 20, 48, 120, and 240 mg groups. VL breakthroughs (>/=1 log(10) from nadir) were seen in most patients on monotherapy and were caused by NS3/4A variants (R155K, D168V) conferring in vitro resistance to BI201335. Adding PegIFN/RBV at Days 15-28 led to continuous viral load reductions in most patients. In treatment-experienced patients, treatment with BI201335 and PegIFN/RBV achieved VL<25 IU/ml at Day 28 in 3/6, 4/7, and 5/6 patients in the 48, 120, and 240 mg dose groups. VL breakthroughs were observed during triple combination in only 3/19 patients. BI201335 was generally well tolerated. Mild rash or photosensitivity was detected in four patients. Mild unconjugated hyperbilirubinemia was the only dose-dependent laboratory abnormality of BI201335. BI201335 elimination half-life supports once-daily dosing. CONCLUSIONS: BI201335 combined with PegIFN/RBV was well tolerated and induced strong antiviral responses. These results support further development of BI201335 in HCV genotype-1 patients.
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.