Integrase Strand Transfer Inhibitor

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral drugs that specifically target the integrase enzyme, which is essential for the replication of retroviruses such as HIV. The integrase enzyme catalyzes the insertion (integration) of viral DNA into the host cell’s genome—a critical step in establishing infection and enabling viral replication.

INSTIs bind to the active site of HIV integrase after 3′-processing has occurred, where they chelate two divalent metal ions (usually magnesium) required for catalysis. By occupying this site, INSTIs prevent the strand transfer reaction—the step where processed viral DNA is covalently linked to host DNA—thus blocking integration and halting further viral replication.