Antiviral therapy of herpes simplex

Herpes simplex virus (HSV) infections in immunocompromised patients are more severe and invasive than in non-immunocompromised patients. They are characterised by prolonged viral shedding and a tendency to heal more slowly. In addition, resistant viruses are exclusively isolated in immunocompromised patients, requiring other drugs with distinct mechanisms of action. The reference compound for the treatment of HSV infections is acyclovir (ACV) that selectively inhibits HSV DNA replication with low host-cell toxicity. Recently, two molecules, valaciclovir (VACV), the L-valyl ester of ACV and famciclovir (FCV), the diacetyl ester of 6-deoxy-penciclovir (PCV), another potent nucleoside analogue, were developed showing an increased oral bioavailability compared to the original compounds. Foscavir (PFA) and more recently cidofovir (CDV) are drugs that do not need the viral thymidine kinase (TK) to be activated and therefore are the appropriate candidates for the treatment of resistant viruses emerging under acyclovir or penciclovir.