HIV Type 1 Integrase Inhibitors: From Basic Research to Clinical Implications
Oyebisi Jegede 1, John Babu 1, Roberto di Santo 1, Damian J. McColl 1, Jan Weber 1, Miguel E. Quiñones-Mateu 1
1 NULL
*Correspondence: Damian J. McColl, Email not available
Abstract
Similar to other retroviruses, productive infection with HIV-1 requires three key steps in the viralreplication: (i) reverse transcription of viral genomic RNA into viral cDNA by the viral reversetranscriptase; (ii) integration of viral cDNA into host cell genome using the viral integrase; and (iii)cleavage of newly synthesized viral polypeptide by the viral protease into individual viral proteinsduring new virion assembly. Following their discovery, all three viral enzymes were considered astargets for antiretroviral drugs. However, while multiple reverse transcriptase and protease inhibitorshave been used for more than 12 years to treat HIV-infected individuals, only recently has the viralintegrase enzyme emerged as an alternative, clinically validated target to block HIV-1 replication. Herewe review the biology of HIV-1 integration, the mechanisms of action and development of resistanceto integrase inhibitors, and the latest data on the most recent clinical trials involving this promising,novel class of antiretroviral drugs.
