HIV-1 entry - an expanding portal for drug discovery

The advent of highly active antiretroviral therapy (HAART)-combinations of protease and reverse transcriptase inhibitors-provided a potent and clinically effective method of suppressing viral load in HIV-1- infected individuals. However, although initially successful, a broader clinical experience has revealed limitations in this therapeutic regimen, with up to 40% of treated individuals ultimately failing to sustain control over viral replication. Significant advances in understanding the process by which HIV-1 enters host cells have brought into clear focus a target for drug discovery not represented in the current clinical armamentarium. In this article, the mechanism of HIV-1 entry is reviewed in the context of representative antiviral agents that interfere with key steps in this process.