Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Cento, Valeria; Tontodonati, Monica; Di Maio, Velia Chiara; Bellocchi, Maria Concetta; Valenti, Fabrizio; Manunta, Alessandra; Fortuna, Serena; Armenia, Daniele; Carioti, Luca; Antonucci, Francesco Paolo; Bertoli, Ada; Trave, Francesca; Cacciatore, Pierluigi; Angelico, Mario; Navarra, Pierluigi; Neumann, Avidan U.; Vecchiet, Jacopo; Parruti, Giustino; Babudieri, Sergio; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca
• Is Part Of: Digestive and liver disease. Volume 47:Issue 3(2015)
• Page Start: 233
• Page End: 241
• Publication Date: 2015-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2014.12.004
• Languages: English
• ISSNs: 1590-8658

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients.</p> </sec> <sec> <title id="sect0015">Aim</title> <p id="spar0010">To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure.</p> </sec> <sec> <title id="sect0020">Methods</title> <p id="spar0015">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.</p> </sec> <sec> <title id="sect0025">Results</title> <p id="spar0020">13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir + pegylated-interferon-α + ribavirin.</p> <p id="spar0025">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 <1 log IU/ml decay between 48 h and 2 weeks, and HCV-RNA >100 IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.</p> <p id="spar0030">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 <26% at 48 h) or major (V36M/A-R155K: prevalence, 99.8% at week 2) variants.</p> </sec> <sec> <title id="sect0030">Conclusions</title> <p id="spar0035">Following telaprevir administration, first-phase HCV-RNA decay is consistent with mutational freeze and limited/no viral replication, while second-phase is significantly slower in failing patients (with appearance of resistance), suggesting the usefulness of early HCV-RNA monitoring.</p> </sec> </abstract>