Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-naïve Patients Infected with Genotype 1b Hepatitis C Virus.
- Author:
Ye WANG
;
Hui-Ying RAO
;
Xing-Wang XIE
;
Lai WEI
1
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Antiviral Agents; therapeutic use; Benzimidazoles; therapeutic use; China; Drug Resistance, Viral; genetics; Female; Fluorenes; therapeutic use; Genotype; Hepacivirus; drug effects; pathogenicity; Hepatitis C; drug therapy; High-Throughput Nucleotide Sequencing; Humans; Imidazoles; therapeutic use; Male; Middle Aged; Polymorphism, Genetic; genetics; Simeprevir; therapeutic use
- From: Chinese Medical Journal 2015;128(19):2625-2631
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDIt 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.
METHODSDirect 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).
RESULTSOne 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.
CONCLUSIONSThe 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.