A perspective on antiviral resistance

More than 25 years after the licensure of aciclovir and then penciclovir, followed by their respective prodrugs valaciclovir and famciclovir, cases of clinically relevant resistance to these drugs in immunocompetent individuals remain very rare. The aim of this review is to focus on the mechanism of action of these anti HSV drugs and then briefly compare this favourable outcome with that of CMV, HIV, HBV and influenza. A central theme is that resistance is an epiphenomenon of failure to suppress virus replication, so that improved potency and selectivity should be prioritised when developing new drugs rather than activity against resistant strains per se.