HCV Mutation Detail Information

Virus Mutation HCV Mutation P58H


Basic Characteristics of Mutations
Mutation Site P58H
Mutation Site Sentence The mutations against DCV R30Q (9.1%), P58H (6.1%) and Q62E (6.1%) were observed into NS5A, and for SOF the mutations A421V (10.6%), L159F (6.4%) and C316N (6.4%) were present inside NS5B viral protein.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NS5A
Standardized Encoding Gene NS5A
Genotype/Subtype 1
Viral Reference AF011753.1;D50481.1
Functional Impact and Mechanisms
Disease HCV Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment DCV
Location Brazil
Literature Information
PMID 31523019
Title Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil
Author Aguiar BF,Campos GRF,Rodrigues JPV,Marques NN,Molina BF,Bittar C,Souza FF,Martinelli ALC,Rahal P,Pereira LRL
Journal Clinics and research in hepatology and gastroenterology
Journal Info 2020 Jun;44(3):329-339
Abstract BACKGROUND: The World Health Organization estimates that 1% of the world population (71 million) is infected with hepatitis C virus (HCV). In 2015, three direct-acting antivirals (DAAs), simeprevir (SMV), sofosbuvir (SOF) and daclatasvir (DCV) were included in the Brazilian protocol for the treatment of chronic hepatitis C. Despite the fact that the use of these drugs is associated with higher treatment response rates and with lower incidence of side effects, studies have shown the association between the presence of viral resistance mutations and the failure of pharmacological treatment. AIM: This way, this study aimed to evaluate the safety and effectiveness of treatment for HCV genotypes 1a and 1b infected patients with these DAAs, also analyzing the occurrence and prevalence of baseline resistance associated substitutions (RAS), observing the impact of these mutations into the treatment success. METHODS: Clinical data were collected from all the 262 HCV infected patients included for comparative analysis, while serum samples collected from 144 of these individuals, before treatment, were submitted to molecular biology approaches for mutation analysis into NS3, NS5A and NS5B regions. RESULTS: Regarding the treatment regimens, 49.6% of the patients received SOF+DCV+/-ribavirin and 50.4% used SOF+SMV+/-ribavirin. The sustained virological response at 12 weeks post-treatment (SVR12) rate was 92.7% (93.9% for SOF plus DCV and 91.7% for SOF plus SMV). No clinical or laboratorial factor was statistically associated with SVR. The most common adverse reactions were haematological events, nausea/vomiting, headache and asthenia. Out of 144 blood samples, 70 (48.6%) had detected RAS, 34.8% treated with SOF+DCV+/-ribavirin and 61.3% SOF+SMV+/-ribavirin. The resistance mutations against SMV were detected into NS3: substitutions G122S (28%), I170V (22.7%), Y56F (17.3%) and V132I (14.7%). The mutations against DCV R30Q (9.1%), P58H (6.1%) and Q62E (6.1%) were observed into NS5A, and for SOF the mutations A421V (10.6%), L159F (6.4%) and C316N (6.4%) were present inside NS5B viral protein. Four patients did not reach SVR, three of them presented viruses carrying RAS (1 treated with SOF+DCV and 2 with SOF+SMV). Some of these mutations, like R30Q (present in relapsing samples) and L159F, are well known by their influence on antiviral resistance, while others, like C316N, have a compensatory effect on viral fitness, maintaining these baseline RAS. CONCLUSION: The use of treatment regimens composed of SOF and DCV or SOF and SMV showed a high SVR rate, despite of a high rate of RAS, and a good tolerability profile in patients with HCV genotype 1. However, the high occurrence of baseline RAS observed in this casuistic is still a concern and studies like this show the necessity to understand how they are maintained in the population and to direct more efficiently the use of DAAs.
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.