Mechanisms of Nonretroviral Resistance

Abstract

The development of the nucleoside analogues acyclovir and penciclovir was a milestone in antiviral therapy. Their success in treating herpes simplex virus (HSV) and varicella zoster virus (VZV) demonstrated the potential of drug therapy in the management of viral infections. The subsequent development of the nucleoside analogue ganciclovir, and its prodrug valganciclovir, provided effective antiviral therapy against human cytomegalovirus (CMV) infections. Newer agents such as the pyrophosphate analogue foscarnet and nucleotide analogue cidofovir, that bypassed the need for viral protein kinase phosphorylation for activation, offered an even wider antiviral spectrum of activity. Since the introduction of these groundbreaking antiviral medications, drug-resistant isolates of HSV and VZV have been reported, primarily among severely immunocompromised patients such as transplant recipients and patients with human immunodeficiency virus (HIV). Other antiviral agents, developed to treat a variety of additional viruses, are now in widespread use, but their success has also been challenged by the emergence of drug resistance. In this chapter, we review antiviral therapies for HSV and VZV, mechanisms of drug resistance, and strategies for managing skin infections with resistant strains. We also briefly discuss the influenza virus and its mechanism of resistance to drug therapy.