Dolutegravir (an integrase strand transfer inhibitor, INSTI) is preferred as first-line ART over older INSTIs (raltegravir) because:
- A Dolutegravir is renally eliminated with no drug interactions compared to hepatic metabolism of raltegravir
- B Dolutegravir specifically targets HIV-1 integrase, while raltegravir inhibits both HIV-1 and HIV-2 integrase equally
- C Dolutegravir has a higher genetic barrier to resistance due to its tighter binding to the integrase-DNA complex ✓
- D Dolutegravir is a non-competitive integrase inhibitor while raltegravir is competitive
Correct answer: C. Dolutegravir has a higher genetic barrier to resistance due to its tighter binding to the integrase-DNA complex
Explanation
Dolutegravir binds to the integrase-DNA complex (the intasome) with slower dissociation kinetics than raltegravir, effectively competing with the viral DNA end that needs to be transferred. This tight binding raises the genetic barrier to resistance — single mutations (like Y143, Q148, N155) that confer high-level resistance to raltegravir do not significantly affect dolutegravir. Clinically, resistance to dolutegravir has been extremely rare in treatment-naive patients, making it the preferred INSTI in WHO guidelines.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.