Chemotherapy of varicella zoster virus infections

Varicella zoster virus (VZV), a member of the herpesvirus family, is responsible for a primary infection (varicella, chickenpox) as well as a recurrent disease (zoster, shingles). The course of varicella is generally benign in immunocompetent patients. For zoster, post-herpetic neuralgia is the most common complication. In immunocompromised patients, particularly patients suffering from the acquired immune deficiency syndrome (AIDS), transplant recipients and cancer patients, VZV infections can be life-threatening. For these patients and also for immunocompetent patients at risk, such as pregnant women or premature infants, the current treatment of choice is based on acyclovir (ACV) by either intravenous or oral route. The low oral bioavailability of ACV, as well as the emergence of drug-resistant virus strains, have stimulated efforts towards the development of new compounds for the treatment of VZV infections. Among these new compounds, penciclovir (PCV) and its oral prodrug form, famciclovir (FCV), 882C87, BVDU, BVaraU and the oral prodrug form of acyclovir (valacyclovir) rank among the most promising. Like ACV itself, all these drugs are dependent on the virus-encoded thymidine kinase (TK) for their intracellular activation (phosphorylation), and, therefore, cross-resistance to these drugs may be expected for those virus mutants that are TK-deficient and thus resistant to ACV. However, such TK(-) VZV mutants are still sensitive to the acyclic nucleoside phosphonates (i.e. HPMPC), which for their phosphorylation do not depend on the virus-encoded TK. The molecular targets within the viral replicative cycle, with which these different compounds interact, are discussed, as are the in vitro activity and in vivo efficacy of the most promising compounds. Other aspects, such as vaccination and passive immunization, are briefly mentioned.