Integrase Inhibitors Suppress SHIV Replication in Rhesus Macaques

To date, drugs licensed for treatment of HIV diseasebelong to the classes of entry inhibitors, nucleosideand non-nucleoside reverse transcriptaseinhibitors (NRTI and NNRTI), or protease inhibitors(PI). Antiviral resistance in treated and newly infectedpatients justifies the development of new anti-HIVdrugs preferentially targeting alternative steps of theviral replication cycle. Integration of the proviral DNAinto the host chromosome through the action of thethird viral enzyme, integrase, is an essential step andprovides an attractive antiviral target. After binding tothe viral DNA, integrase will remove the 3’GT dinucleotidesfrom both long terminal repeat (LTR) endsin the 3’ processing reaction; after transport into thenucleus, integrase will insert the trimmed viral DNAinto the host DNA during the strand-transfer reaction.