Mathematical modelling of HCV infection: what can it teach us in the era of direct-acting antiviral agents?

HCV infection is a major cause of chronic liver disease and affects nearly 170 million people worldwide. Whereas the previous standard of care with pegylated interferon and ribavirin had a modest effectiveness, the recent approval of two highly potent protease inhibitors and the ongoing development of dozens of direct-acting antiviral agents (DAAs) constitute a major milestone for HCV therapy. Mathematical modelling of viral kinetics under treatment has played an instrumental role in improving our understanding of virus pathogenesis and in guiding drug development. Here, we review the current state of HCV kinetic modelling, and challenges to the standard biphasic viral decline model that arise when fitting viral kinetic models to data obtained with DAAs.