Dolutegravir, an HIV integrase strand transfer inhibitor (INSTI), is preferred over first-generation raltegravir in highly treatment-experienced patients because:

• A Dolutegravir requires pharmacokinetic boosting with ritonavir for efficacy
• B Dolutegravir has a higher genetic barrier to resistance; mutations conferring raltegravir resistance do not reduce dolutegravir susceptibility at typical concentrations ✓
• C Dolutegravir inhibits both integrase and reverse transcriptase
• D Dolutegravir is the only INSTI active against HIV-2

Explanation

Dolutegravir has a slower dissociation rate from the integrase-DNA complex compared to raltegravir/elvitegravir; this translates to a higher genetic barrier to resistance. The primary mutations conferring resistance to first-generation INSTIs (N155H, Q148H/R/K, Y143R) do not substantially affect dolutegravir binding. Acquiring resistance to dolutegravir typically requires additional compensatory mutations (e.g., G140S + Q148H), making resistance emergence rare. Dolutegravir does not require boosting.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.