Brand Name: Tivicay Generic Name: dolutegravir Manufacturer: ViiV Healthcare Drug Class: Antiretroviral Agent, Integrase Inhibitor

Mechanism of Action: Dolutegravir inhibits the catalytic activity of HIV integrase, which is an HIV encoded enzyme required for viral replication. Integrase is one of the three HIV-1 enzymes required for viral replication. Integration of HIV into cellular DNA is a multi-step process. First, the assembly of integrase in a stable complex with the viral DNA occurs. Second, the terminal dinucleotides from each end of the viral DNA are removed by endonucleolytic processing. Lastly, the viral DNA 3' ends are covalently linked to the cellular (target) DNA by strand transfer. The last two processes, which are catalytic, require integrase to be appropriately assembled on a specific viral DNA substrate. Inhibition of integrase by dolutegravir prevents the covalent insertion, or integration, of unintegrated linear HIV DNA into the host cell genome preventing the formation of the HIV provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection.