title: Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-naïve Patients Infected with Genotype 1b Hepatitis C Virus.
abstract: BACKGROUND
  It has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-naÏve GT1b CHC patients.
  
  
  METHODS
  Direct sequencing and ultra-deep sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum samples of treatment-naÏve patients infected with genotype 1b hepatitis C virus (HCVs).
  
  
  RESULTS
  One hundred and sixty CHC patients were studied. Complete sequence information was obtained for 145 patients (NS3), 148 patients (NS5A), and 137 patients (NS5B). Treatment-failure associated variants of DAAs were detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor); 10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.
  
  
  CONCLUSIONS
  The majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Rao
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Xie
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Beijing 100044, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates; D002681:China; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity*; D006526:Hepatitis C / Q000188:drug therapy; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011759:Pyrrolidines; D000069616:Simeprevir / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011759:Pyrrolidines; C586541:ledipasvir; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir