Dolutegravir is preferred over raltegravir as an HIV integrase inhibitor. The key pharmacological advantage of dolutegravir is:

• A Dolutegravir inhibits both integrase and reverse transcriptase (dual-class inhibition)
• B Higher genetic barrier to resistance (requires at least 2 mutations for clinically significant resistance), and longer half-life enabling once-daily dosing without boosting ✓
• C Dolutegravir is active against raltegravir-resistant variants without any exception
• D Dolutegravir is the only integrase inhibitor not metabolized by CYP3A4

Explanation

Dolutegravir (second-generation integrase strand transfer inhibitor, INSTI) has a higher genetic barrier to resistance than raltegravir/elvitegravir — a single Q148H/K/R mutation reduces its activity but does not fully eliminate it, and at least two secondary mutations are required for high-level resistance. It has a longer plasma half-life (~14 hours) allowing once-daily dosing without pharmacokinetic boosting. Raltegravir requires twice-daily dosing. However, against high-level raltegravir resistance mutations (Q148+secondary mutations), dolutegravir may also lose activity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.