Antiviral resistance and direct-acting antiviral agents for HCV

Amanda Aloia, Michael Beard, Stephen Locarnini

    Research output: Contribution to journalReview articlepeer-review

    24 Citations (Scopus)


    Direct-acting antiviral (DAA) agents specifically target viral proteins. Two DAAs have been already been approved for the treatment of HCV infection and many more are in development. DAA treatment of HCV infection, however, leads to the selection of viral variants (produced by the error-prone HCV polymerase) that are resistant to the DAA agent in use. The selection of DAA-resistant HCV variants has been studied extensively in vitro and in vivo. Common amino acid substitution sites in each of the non-structural proteins are associated with DAA-resistance: D168, A155, A156 and V36 in NS3 protease; L31 and Y93 in NS5A; S282, S96, P495, M423, M414 and C316 in NS5B. In this review we cover the basic principles of DAA resistance, summarise the available resistance data for the various classes of DAAs and discuss the potential of DAA combination therapy for overcoming DAA-resistance, resulting in major advances in the treatment of HCV.

    Original languageEnglish
    Pages (from-to)1147-1162
    Number of pages16
    JournalAntiviral Therapy
    Issue number6 PART B
    Publication statusPublished - 2012


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