HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study

Research output: Contribution to journalArticle

Abstract

Background: The impact of pre-existing variants in hepatitis C virus (HCV) quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of treatment with direct acting antiviral agents (DAA) is debated and it is complicated by the lack of knowledge of quasispecies distribution between the viral reservoir (liver) and the circulating compartment. Objective: To evaluate NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver biopsy samples. Plasma dynamics were also analyzed during therapy and after its suspension.Study design Ultra-deep pyrosequencing (UDPS) was performed in two HCV genotype 1a patients who received telaprevir (TVR)-based therapy and developed treatment failure due to TVR-resistance. Results: In both patients the baseline diversity of NS3 quasispecies in plasma was higher than in liver (183.6×10-4 vs 47.8×10-4 and 246.0×10-4 vs 55.0×10-4 nt substitution/site, respectively, p

Original languageEnglish
Pages (from-to)60-65
Number of pages6
JournalJournal of Clinical Virology
Volume72
DOIs
Publication statusPublished - Nov 1 2015

Keywords

  • Diversity
  • HCV
  • NS3
  • Resistance associated mutations
  • Ultra-deep pyrosequencing
  • Viral quasispecies

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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