Molecular Pharmacology of Nucleoside and Nucleotide HIV-1 Reverse Transcriptase Inhibitors

Abstract

In 1985, 3’-azido-thymidine (AZT, zidovudine) was identified as the first nucleoside analog with activity against human immunodeficiency virus type 1 (HIV-1) (Mitsuya et al., 1985, 1987; Mitsuya & Broder, 1986), the etiologic agent of acquired immunodeficiency syndrome (BarreSinoussi et al., 1983; Gallo et al., 1984). This seminal discovery showed that HIV-1 replication could be suppressed by small molecule chemotherapeutic agents, and provided the basis for the field of antiviral drug discovery. Zidovudine was approved by the United States of America Food and Drug Administration for the treatment of HIV-1 infection in 1987. In the 26 years since, an additional seven nucleoside or nucleotide analogs have been approved, while several others are in clinical development. This chapter will provide a summary of the molecular pharmacology of these compounds.