Dolutegravir is preferred over first-generation integrase strand transfer inhibitors (raltegravir/elvitegravir) for HIV treatment because:
- A Dolutegravir requires boosting with ritonavir/cobicistat for adequate plasma levels unlike raltegravir
- B Dolutegravir acts on HIV reverse transcriptase as well as integrase, giving a dual mechanism
- C Dolutegravir has a higher genetic barrier to resistance due to binding a distinct and more conserved site within the integrase catalytic core ✓
- D Dolutegravir is a CCR5 co-receptor antagonist preventing viral entry along with integrase inhibition
Correct answer: C. Dolutegravir has a higher genetic barrier to resistance due to binding a distinct and more conserved site within the integrase catalytic core
Explanation
Dolutegravir (second-generation INSTI) has a higher genetic barrier to resistance than raltegravir/elvitegravir (first-generation INSTIs). It binds more tightly to the integrase active site and requires multiple (2+) specific mutations before significant resistance emerges, whereas raltegravir/elvitegravir can be overcome by single N155H, Q148H/R/K, or Y143R mutations. Dolutegravir does NOT require pharmacokinetic boosting (unlike elvitegravir which needs cobicistat). It is only an integrase inhibitor, not RT inhibitor or CCR5 antagonist.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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