Resistance to Direct-Acting Antivirals |
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Authors: | Jean-Michel Pawlotsky |
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Institution: | 1. National Reference Center for Viral Hepatitis B, C and D, Department of Virology, H?pital Henri Mondor, Universit?? Paris-Est, Cr??teil, France 2. INSERM U955, Cr??teil, France 3. Department of Virology, H?pital Henri Mondor, 51 avenue du Mar??chal de Lattre de Tassigny, 94010, Cr??teil, France
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Abstract: | Viral resistance corresponds to the selection, during treatment, of pre-existing viral variants less susceptible to the drug??s inhibitory activity because they bear amino acid substitutions altering the drug target. Hepatitis C virus (HCV) drugs in development can be split into two groups according to their barrier to resistance. Direct-acting antiviral drugs with a low barrier to resistance include first-generation NS3-4A protease inhibitors, non-nucleoside inhibitors of HCV RNA-dependent RNA polymerase and first-generation NS5A inhibitors. HCV drugs with a high barrier to resistance include nucleoside/nucleotide analogues, possibly second-generation protease and NS5A inhibitors, and host-targeted agents, such as cyclophilin inhibitors or microRNA-122 antagonists. This article reviews recent findings that add to our knowledge and understanding of HCV resistance to direct-acting antiviral drugs and discusses them in the context of new therapeutic strategies, with and without pegylated interferon-?? and/or ribavirin. |
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