A 32-year-old man with newly diagnosed HIV-1 infection (CD4 count 350 cells/μL, viral load 95,000 copies/mL) presents to the antiretroviral clinic. He has no prior antiretroviral exposure and no opportunistic infections. What is the drug of choice as the integrase strand transfer inhibitor (INSTI) component of his first-line regimen?

Explanation

## First-Line INSTI Selection in Treatment-Naïve HIV **Key Point:** Dolutegravir is the preferred integrase inhibitor for first-line antiretroviral therapy in treatment-naïve patients with no resistance mutations. ### Why Dolutegravir is Preferred 1. **Superior barrier to resistance**: Requires 2 mutations for resistance to emerge, compared to raltegravir (1 mutation) 2. **Pharmacokinetics**: Once-daily dosing (50 mg) vs raltegravir's twice-daily requirement 3. **Efficacy**: Non-inferior to or superior to other INSTIs in clinical trials (SINGLE, SPRING-2, FLAMINGO trials) 4. **Tolerability**: Minimal drug interactions; can be used with most antiretrovirals 5. **Cost-effectiveness**: Now widely available as generic in India ### Comparison of INSTIs | INSTI | Dosing | Barrier to Resistance | First-Line Use | Notes | |-------|--------|----------------------|-----------------|-------| | **Dolutegravir** | Once daily (50 mg) | High (2 mutations) | **Yes** | Preferred choice | | Raltegravir | Twice daily (400 mg) | Low (1 mutation) | Alternative | Older agent; more dosing burden | | Elvitegravir | Once daily (150 mg) | Moderate | No | Requires boosting; less used | | Bictegravir | Once daily (50 mg) | High | Alternative | Newer; limited data in India | **High-Yield:** Dolutegravir is the WHO-recommended first-line INSTI globally and is now standard-of-care in most resource-limited settings including India [cite:WHO 2023 ART Guidelines]. **Clinical Pearl:** Dolutegravir should be taken 2 hours apart from polyvalent cations (Ca²⁺, Mg²⁺, Fe²⁺) and antacids to avoid absorption reduction. **Warning:** Raltegravir, while effective, requires twice-daily dosing and has a lower genetic barrier to resistance — it is now reserved for special situations (e.g., pregnancy in some guidelines, integrase resistance).