Inhibitors of human immunodeficiency virus integration

Publisher Summary This chapter attempts to highlight some of the more recent advances with a focus on those small molecules that have been validated as bona fide integration inhibitors and their potential as drug-development leads. Recent understanding of the mechanism of action intrinsic to different classes of integrase inhibitors, i.e., inhibition of assembly, 3 1 end processing and strand transfer, has facilitated the identification of compounds that are bona fide inhibitors of integration in cell culture and has proven that inhibiting integrase strand transfer leads to a profound antiviral effect. Studies on these inhibitors have led to additional insights into the mechanism of integrase activity both in vitro and in HIV-1 infected cells. Most importantly, the demonstration that strand-transfer inhibitors with potent activity against HIV-1 in cell culture and favorable pharmacokinetic properties are efficacious in a rhesus model suggests that this mechanism will yield novel antiretroviral agents and provide a new class of therapies to treat HIV-1 infection.