Resistance patterns and genetic variations in patients with hepatitis C virus: emerging role of telaprevir

C Argentini, D Genovese, S Catone

Istituto Superiore di Sanità, Department of Therapeutic Research and Medicine Evaluation, Rome, Italy

Abstract: High genetic variability is a characteristic of hepatitis C virus (HCV) infection: infinite virus isolates are classified into six genotypes plus an emerging seventh one, and an indefinite number of subtypes. The variability is directly connected to the environmental adaptation of infective agents or to the change induced by antiviral therapies. During therapy, wild type isolates are substituted by resistant mutants that are able to maintain the infection. The standard therapy (pegylated interferon [PEG-IFN] and ribavirin) only partially eradicates HCV infection. However, particularly in genotype 1 infection, the rate of uncured patients remains high (between 50% and 60%). Specifically targeted antiviral therapies for HCV infection (STAT-C) consist of developing new antivirals aimed at blocking the virus proteins involved in different replication steps. Telaprevir is an anti-NS3-NS4 protease in phase III trials and represents a promising therapy, especially when associated with PEG-IFN and ribavirin. In vitro and in vivo research studies describe mutations that confers resistance to telaprevir in NS3-NS4 protease (V36A/M/L/G, F43, T54A, R130K, R155L/K/T/Q, A156T/S/V, V170A and Q195K). The emergence of these mutations describes the adaptation capability of HCV infection.

Keywords: HCV, telaprevir, resistance, antiviral therapy, virus adaptation