Genotypic resistance testing of HCV – is there a clinical need?

Persistent infections with the hepatitis C virus (HCV) pose a profound global public health burden. In the past 5 years treatment of chronic hepatitis C has dramatically changed. Novel direct-acting antivirals (DAAs) specifically inhibiting viral enzymes or factors that are essential for the viral replication cycle have been developed and licensed for hepatitis C therapy. These novel drugs target the viral NS3/4A protease, the NS5B RNA-dependent RNA-polymerase or the replication factor NS5A. Combinations of DAAs against these targets are highly efficacious achieving virus elimination in the majority of treated patients. In countries where affordable, this rapid clinical development virtually replaced earlier interferon (IFN)-α based therapy that had been in use as standard of care for the last 25 years. With the approval of DAAs for the treatment of chronic hepatitis C the question emerged whether resistance-associated substitutions (RASs) might be of clinical relevance. Here, we discuss the available evidence for the possible benefit of resistance genotyping prior to therapy to optimize treatment of chronic hepatitis C.