Systemic antivirals in herpesvirus infections

Over the last few years we have seen the advent of effective antiviral drug therapy, the major ramifications being in the area of herpes infections. Acyclovir has become an established part of clinical practice, and other compounds are being increasingly used in the immunocompromised host. An effective vaccine is available for chickenpox, but herpes simplex and cytomegalovirus vaccines are still in early development. Thus, antiviral agents will continue to play a major role in the management of all herpesvirus infections for the foreseeable future. Current work includes the development of increased bioavailability prodrugs (BW 256, famciclovir), which are converted to active drug once absorbed, enabling rapid high serum levels, and hence may turn out to have increased efficacy in HSV- and VZV-induced diseases, for which oral acyclovir currently is the treatment of choice. Markedly increased efficacy against VZV in vitro has been demonstrated by two current agents under study (BVaraU, BW 882). HPMPC is now entering clinical trials with a markedly improved efficacy profile against CMV and HSV in animal models. Finally, drug combinations that are being investigated in AIDS may offer a means to avoid resistance in herpes infections in immunocompromised patients.