Dolutegravir (DTG) is preferred in first-line HIV regimens over older integrase strand transfer inhibitors (INSTIs). Which property makes DTG superior in terms of resistance?

• A DTG also inhibits HIV protease, preventing resistance at multiple steps
• B Higher genetic barrier to resistance — requires multiple mutations in the integrase gene (rather than single Q148 or Y143 mutations) to develop clinically significant resistance ✓
• C DTG is a non-nucleoside reverse transcriptase inhibitor and therefore shares no resistance pathway with integrase inhibitors
• D DTG is excreted unchanged renally, preventing development of intracellular resistant mutants

Explanation

Dolutegravir has a higher genetic barrier to resistance than first-generation INSTIs (raltegravir, elvitegravir): single integrase mutations at Q148H/K/R do not reduce DTG activity unless accompanied by additional mutations (e.g., G140S+Q148H). This means resistance rarely emerges in treatment-naive patients on DTG-based regimens. Raltegravir and elvitegravir have a lower barrier — single mutations can cause clinically relevant resistance. DTG does not inhibit protease or reverse transcriptase. Its metabolism is hepatic (CYP3A4/UGT1A1).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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