Integrase inhibitors

Approved: Dolutegravir (DTG) !(image)./resources/AIDSinfo.gif!, Elvitegravir (EVG) !(image)./resources/AIDSinfo.gif!, Raltegravir (RAL) !(image)./resources/AIDSinfo.gif!

Inhibition mechanism

HIV integrase has become an emerging drug target. After reverse transcription, the integrase protein assembles with viral DNA to form a stable complex, termed the pre-integration complex (PIC), and enters the host nucleus. There, integrase mediates the integration of complementary DNA (cDNA) into the host genome in a two-step process. First, two nucleotides are excised from the 3'-ends of viral DNA. Then, the covalent insertion of HIV viral DNA to the host chromosome occurs. Integrase inhibitor Raltegravir interacts with divalent metals within the active site of HIV-1 integrase. This interaction inhibits the insertion of viral DNA into the host chromosome (strand transfer process). Elvitegravir is also a specific inhibitor of the strand-transfer step of HIV integration. Dolutegravir (DTG) is the only second-generation INSTI with FDA approval in 2013.

Side-effects and metabolism

The most common side effects of integrase inhibitors are gastrointestinal events, including nausea/vomiting or diarrhea as well as headache, nerveous system and neuropsychiatric effects