The emerging field of HCV drug resistance.

Abstract:

BACKGROUND:With 170 million people infected worldwide and an inadequate current standard of care, hepatitis C virus (HCV) infection represents a major unmet medical need. Multiple companies are working on the discovery and development of specific HCV antiviral drugs, including inhibitors of HCV polymerase, protease and NS5A. Because of the error-prone nature of viral RNA replication, resistance mutants will develop that could present a potentially significant challenge to developing antiviral treatment regimens. OBJECTIVE:Here, we review the major drug classes currently in preclinical and clinical development and the resistance mutations specific for each class that have been identified from cell culture and/or in vivo studies. METHODS:We have analyzed currently available scientific literature to create a comprehensive review of the current state of the art in the field of HCV resistance to specific antiviral agents, in vitro and in vivo. RESULTS/CONCLUSION:Most specific HCV inhibitors described in the literature can select resistant viral variants in cell culture and in the clinic. Interplay of a mutant's fitness and its level of resistance will determine its clinical importance. Combinations of non-cross-resistant classes of drugs will be key to successful antiviral therapy. The number of drugs in a combination as well as the optimal duration of antiviral treatment, are important issues that need to be addressed in future studies.

authors

Koev G,Kati W

doi

10.1517/13543784.17.3.303

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

303-19

issue

3

eissn

1354-3784

issn

1744-7658

journal_volume

17

pub_type

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