Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice

Valeria Cento, Monica Tontodonati, Velia Chiara Di Maio, Maria Concetta Bellocchi, Fabrizio Valenti, Alessandra Manunta, Serena Fortuna, Daniele Armenia, Luca Carioti, Francesco Paolo Antonucci, Ada Bertoli, Francesca Trave, Pierluigi Cacciatore, Mario Angelico, Pierluigi Navarra, Avidan U. Neumann, Jacopo Vecchiet, Giustino Parruti, Sergio Babudieri, Carlo Federico PernoFrancesca Ceccherini-Silberstein

Research output: Contribution to journalArticle

Abstract

Background: The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients. Aim: To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure. Methods: Viraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing. Results: 13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir. +. pegylated-interferon-α. +. ribavirin.Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2]. log. IU/ml within 48. h. Second-phase decay was slower, especially in failing patients: 3/3 showed 100. IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24. h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence

Original languageEnglish
Pages (from-to)233-241
Number of pages9
JournalDigestive and Liver Disease
Volume47
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Drug-resistance
  • Mathematical modelling
  • Protease inhibitors
  • Viral kinetic

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology
  • Medicine(all)

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    Cento, V., Tontodonati, M., Di Maio, V. C., Bellocchi, M. C., Valenti, F., Manunta, A., Fortuna, S., Armenia, D., Carioti, L., Antonucci, F. P., Bertoli, A., Trave, F., Cacciatore, P., Angelico, M., Navarra, P., Neumann, A. U., Vecchiet, J., Parruti, G., Babudieri, S., ... Ceccherini-Silberstein, F. (2015). Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice. Digestive and Liver Disease, 47(3), 233-241. https://doi.org/10.1016/j.dld.2014.12.004