Herpes simplex virus antiviral drug resistance--current trends and future prospects

The various manifestations of herpes simplex virus (HSV) have been widely treated using antiviral agents for more than 40 years. Acyclovir (ACV) is the drug that has been most commonly used to date. When tested in cell culture, the majority of isolates of HSV are sensitive to ACV with ED50 values of approximately 0.1 microg/ml. ACV-resistant strains (defined as having ED50>2 microg/ml) are rarely encountered in clinical practice among normal patients (<1% isolates) and there is no firm evidence, to date, that this incidence is increasing. Resistant HSV occurs much more frequently, however, among immunocompromised patients during treatment (approximately 5% isolates) where this is recognised to be an important clinical problem leading to ineffective therapy. In this review it is argued that the rapid establishment of neuronal latency in the normal pathogenesis of HSV is the key to the low incidence of resistance development and leads to some optimism concerning future trends.