Integrase Inhibitors

Abstract

The fundamental approach to most antiretroviral therapy (ART) is based on a strategy of targeting the function of HIV enzymes critical to viral replication. Three such targets are HIV reverse transcriptase, HIV protease, and HIV integrase. After viral entry into the CD4+ T cell, viral RNA is reverse-transcribed into DNA by HIV reverse transcriptase after which HIV integrase forms a pre-integration complex comprised of virally encoded DNA and other cofactors. HIV integration is a two-step process catalyzed by HIV integrase, the first step consisting of the integrase enzyme removing a nucleotide from each 3′ DNA terminus, resulting in the exposure of reactive hydroxyl groups. Next, the pre-integration complex enters the host cell nucleus where it binds to host DNA, after which the integrase enzyme nicks each strand of the host DNA, exposing the 5′ phosphate end which allows bonding between host and viral DNA. After this step, called integrase strand transfer, is accomplished