Resistance to anti-HCV protease inhibitors

The era of direct acting antiviral therapy for HCV infection has dawned with the recent approval of the NS3 protease inhibitors telaprevir and boceprevir. The development of DAA therapy is an exciting advance for clinicians and patients, but it will also bring new challenges. For the first time, drug resistance has become an issue to consider in the management of HCV. This brief review summarizes the current literature concerning resistance to the HCV NS3 protease inhibitors, both experimental and clinical, and identifies the key questions facing the field.

► The NS3 protease inhibitors telaprevir (TVR) and boceprevir (BOC) are now approved for the treatment of genotype 1 HCV in North America and Europe.
► Resistance variants are selected rapidly with monotherapy.
► Key resistance residues for TVR and BOC include R155, A156, V36 and T54.
► TVR and BOC are therefore used in combination with peginterferon-α and ribavirin (RBV).
► Interferon-free treatment regimens are in development.