Deep sequencing analysis of variants resistant to the non‐structural 5A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection
- 25 February 2014
- journal article
- research article
- Published by Wiley in Hepatology Research
- Vol. 44 (14), E360-E367
- https://doi.org/10.1111/hepr.12316
Abstract
Aim Daclatasvir, a non‐structural (NS)5A replication complex inhibitor, is a potent and promising direct antiviral agent (DAA) for hepatitis C virus (HCV), being most effective in genotype 1b infection. Although it is known that genotype 1b viruses with Y93H and/or L31M/V/F mutations have strong resistance to daclatasvir, it is not known whether there are some clinical background conditions that favor the occurrence of HCV carrying those NS5A mutations. Methods In this study, we carried out deep sequencing analysis of stored sera to determine the presence and significance of daclatasvir‐resistant mutants in 110 genotype 1b HCV‐infected patients with no previous daclatasvir treatment. Results Deep sequencing analysis revealed that the NS5A L31M/V/F and Y93H mutations were present in 13 (11.8%) and 34 (30.9%) of the 110 patients, respectively, and significantly more frequently than in the control plasmid. Simultaneous L31M/V/F and Y93H mutations were detected in four of the 110 patients (3.6%). When the clinical relevance of NS5A resistance was investigated, Y93H was significantly correlated with the IL28B major (TT) genotype of the host (P = 0.042). Conclusion Y93H was detected frequently by deep sequencing in daclatasvir treatment‐naïve patients. Importantly, it seems that the IL28B status of the patients may influence the presence of Y93H mutations, resulting in different treatment responses to daclatasvir.Keywords
This publication has 28 references indexed in Scilit:
- Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment optionsJournal of Hepatology, 2012
- Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevirJournal of Hepatology, 2012
- Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trialThe Lancet Infectious Diseases, 2012
- Preliminary Study of Two Antiviral Agents for Hepatitis C Genotype 1The New England Journal of Medicine, 2012
- Antiviral strategies in hepatitis C virus infectionJournal of Hepatology, 2012
- Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in Humans: In Vitro and In Vivo CorrelationsHepatology, 2011
- Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b–infected null respondersHepatology, 2011
- An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver DiseasesHepatology, 2011
- Recombinant HCV Variants With NS5A From Genotypes 1–7 Have Different Sensitivities to an NS5A Inhibitor but Not Interferon-αGastroenterology, 2011
- Resistance Analysis of the Hepatitis C Virus NS5A Inhibitor BMS-790052 in an In Vitro Replicon SystemAntimicrobial Agents and Chemotherapy, 2010