integrase

Integrase is encoded by the pol gene of retroviruses (along with reverse transcriptase and protease) and is packaged within the virion. After HIV enters a CD4+ T cell and reverse transcriptase converts viral RNA into double-stranded DNA, integrase mediates the insertion of this proviral DNA into the host chromosomal DNA, forming the 'provirus.' This integration is a two-step process: 3' processing (removal of two nucleotides from each 3' end of viral DNA) and strand transfer (covalent joining of viral DNA to host DNA). Once integrated, the provirus becomes a permanent part of the host genome, allowing for either immediate transcription/translation to produce new virions or long-term latency, making complete eradication of HIV extremely difficult (a major challenge in achieving a cure). Because integrase has no human homolog, it is an attractive and selective drug target. Integrase strand transfer inhibitors (INSTIs)—such as raltegravir, elvitegravir, dolutegravir, and bictegravir—block the strand transfer step, preventing viral DNA integration and thus halting the replication cycle. These drugs are now part of first-line antiretroviral regimens due to their high efficacy, good tolerability, and high genetic barrier to resistance (especially dolutegravir and bictegravir). Clinically, integrase inhibitors are used in combination antiretroviral therapy (cART) for HIV-1 infection, often paired with two NRTIs. Understanding integrase function is essential for grasping HIV life cycle, antiretroviral pharmacology, and the molecular basis of viral latency relevant to Step 1 and Step 2 exams.