Successful antiviral therapy continues to be one of the most difficult challenges facing the physician today. The reasons stem from some intrinsic characteristics of the major human viral pathogens. Because all viruses parasitize host cell enzymes and structures to varying degrees, designing or discovering drugs that specifically target the virus without toxicity is difficult. Additionally, many viruses establish a latent infection in the host, during which they are essentially quiescent. Elimination of such latent viruses from the host has so far remained an elusive goal. Some of the most serious viral infections today stem from the reactivation of latent viruses during periods of impaired cell-mediated immunity.

Most of the currently available antiviral agents target the virus by exploiting differences in viral and host replication processes. Many viruses have their own specific DNA polymerases, which are more susceptible to inhibition by specific drugs than the cellular DNA replication enzymes. Thus many antiviral agents are nucleoside analogs. In addition, some of these compounds accumulate preferentially in virus-infected cells or are activated by virusencoded enzymes, increasing their specificity. Nevertheless, unlike many antibacterial agents, most antiviral agents remain far from being “magic bullets” and can have considerable dose-related toxicities.

This chapter describes the Food and Drug Administration (FDA)-approved antiviral drugs, their primary uses, their pharmacokinetics and potential interactions, and the major toxicities associated with their administration. Since 2001, there have been dramatic changes in the approach to the therapy of human immunodeficiency virus type 1 (HIV-1).