Integrase strand transfer inhibitors (INSTIs, e.g., dolutegravir) are preferred agents in first-line HIV ART regimens because:

• A They are the only class that achieves therapeutic levels in the CNS reservoir, clearing latent HIV
• B They directly degrade HIV proviral DNA integrated into host lymphocyte chromosomes
• C They are the only ART class active against both HIV-1 and HIV-2 subtypes
• D They have a high genetic barrier to resistance (especially dolutegravir/bictegravir), minimal drug interactions, and favourable tolerability compared with earlier regimens ✓

Explanation

Second-generation INSTIs (dolutegravir, bictegravir, cabotegravir) have a very high genetic barrier to resistance — the drug binds the integrase active site and stays engaged even when resistance mutations are selected. They are metabolised minimally by CYP enzymes (mostly via UGT1A1), reducing drug-drug interactions. Their once-daily regimens, tolerability, and potency have made them the global first-line recommendation. INSTIs do not degrade proviral DNA.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.