Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

Viruses. 2018 Apr 26;10(5):223. doi: 10.3390/v10050223.

Abstract

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).

Keywords: NS5A; NS5B; direct-acting antivirals; hepatitis C virus; resistance-associated substitutions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Cohort Studies
  • Drug Resistance, Viral / genetics*
  • Female
  • Fluorenes / therapeutic use
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology
  • Hepatitis C / genetics
  • Hepatitis C / virology*
  • Humans
  • Male
  • Middle Aged
  • Portugal / epidemiology
  • Prevalence
  • RNA, Viral / genetics
  • Sofosbuvir
  • Treatment Failure
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use
  • Viral Nonstructural Proteins / genetics*

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • RNA, Viral
  • Viral Nonstructural Proteins
  • ledipasvir, sofosbuvir drug combination
  • Uridine Monophosphate
  • NS-5 protein, hepatitis C virus
  • Sofosbuvir