HIV-1 entry and entry inhibitors as therapeutic agents

Combination antiretroviral therapy for HIV-1 has resulted in dramatic improvement for most patients, but additional therapeutic approaches are needed. Although any step in the replication cycle is a potential target for therapy, currently available drugs target only two steps: reverse transcription and protein processing. Understanding of the mechanisms by which HIV-1 enters target cells has progressed rapidly in recent years, and has provided the basis to develop novel therapeutic approaches to disrupt this step. This article addresses new insights into the mechanism of HIV-1 entry, and focuses on prototype agents under study as representative examples that target specific stages in the entry process.