Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients

PLoS One. 2016 Nov 3;11(11):e0165658. doi: 10.1371/journal.pone.0165658. eCollection 2016.

Abstract

Background: The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.

Methods: Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.

Results: The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.

Conclusions: Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Asian People / genetics
  • Base Sequence
  • Carbamates
  • China
  • Drug Resistance, Viral / genetics*
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / therapeutic use*
  • Interferon-alpha / therapeutic use*
  • Isoquinolines / therapeutic use*
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Pyrrolidines
  • RNA Helicases / antagonists & inhibitors
  • RNA Helicases / genetics
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Sequence Analysis, DNA
  • Serine Endopeptidases / genetics
  • Sulfonamides / therapeutic use*
  • Valine / analogs & derivatives
  • Viral Load / drug effects
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / genetics*
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Interferon-alpha
  • Isoquinolines
  • NS3 protein, flavivirus
  • Pyrrolidines
  • Recombinant Proteins
  • Sulfonamides
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • NS-5 protein, hepatitis C virus
  • Serine Endopeptidases
  • RNA Helicases
  • Valine
  • daclatasvir
  • peginterferon alfa-2a
  • asunaprevir

Grants and funding

This study was supported by the 12th Five-Year Plan of the National Major Project for Infectious Diseases Control (no. 2012ZX10002003), National Natural Science Foundation of China (no. 81373056), Beijing Municipal Science and Technology Commission of major projects (no. D141100000314002 and D141100000314005) and the Postdoctoral Programs Foundation of China (no. 2014M560859). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.