Dolutegravir is preferred over raltegravir/elvitegravir in antiretroviral therapy because of its higher genetic barrier to resistance. The target of all integrase strand transfer inhibitors (INSTIs) is:

• A HIV reverse transcriptase; INSTIs block the RNA-dependent DNA polymerase activity
• B HIV integrase catalytic domain; INSTIs chelate the two Mg2+ ions in the DDE catalytic triad, blocking the strand transfer step in which viral DNA integrates into host chromosomal DNA ✓
• C HIV protease; INSTIs prevent cleavage of the gag-pol polyprotein into mature viral proteins
• D CCR5 co-receptor on host T-cells; INSTIs prevent viral attachment and entry

Explanation

Integrase strand transfer inhibitors (INSTIs — raltegravir, elvitegravir, dolutegravir, bictegravir) target the catalytic core of HIV-1 integrase. Integrase contains a DDE motif (Asp64, Asp116, Glu152) that coordinates two Mg2+ ions essential for 3'-processing and strand transfer reactions. INSTIs chelate these Mg2+ ions within the integrase-viral DNA complex, competitively displacing the target host DNA and blocking insertion of the viral DNA into the host chromosome. Dolutegravir's wider arc of binding allows it to tolerate mutations that confer resistance to first-generation INSTIs.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.