A 32-year-old man newly diagnosed with HIV-1 infection presents to the antiretroviral clinic. CD4 count is 350 cells/μL and viral load is 85,000 copies/mL. He has no opportunistic infections and normal renal and hepatic function. What is the preferred first-line antiretroviral regimen for this patient?

## First-Line ART Regimen Selection **Key Point:** Current WHO and Indian National AIDS Control Organization (NACO) guidelines recommend an integrase inhibitor-based regimen as the preferred first-line therapy for treatment-naïve patients with CD4 >50 cells/μL. ### Rationale for Dolutegravir-Based Regimen **High-Yield:** Dolutegravir (an integrase strand transfer inhibitor, INSTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) — specifically tenofovir and lamivudine — is now the gold standard first-line regimen because: 1. **Superior efficacy**: Dolutegravir achieves faster viral suppression and higher rates of undetectable viral load compared to efavirenz or protease inhibitors. 2. **Better tolerability**: Fewer CNS side effects (compared to efavirenz) and no need for ritonavir boosting. 3. **Genetic barrier**: High barrier to resistance; single mutations rarely confer resistance. 4. **Pill burden**: Once-daily dosing improves adherence. 5. **Drug interactions**: Minimal interactions with other medications. ### NRTI Backbone: Tenofovir + Lamivudine **Clinical Pearl:** Tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) paired with lamivudine (3TC) is the preferred dual-NRTI backbone because: - Potent and well-tolerated - Extensive clinical data supporting efficacy - TDF requires monitoring of renal function and bone density; TAF has better renal/bone safety profile - Both have low pill burden and once-daily dosing options ### Comparison of Third Agents | Agent Class | Drug | Advantages | Disadvantages | Current Role | |---|---|---|---|---| | INSTI | Dolutegravir | Rapid suppression, high barrier, once-daily, minimal interactions | Rare integrase resistance | **First-line** | | NNRTI | Efavirenz | Older data, once-daily | CNS toxicity, teratogenic, resistance emerges faster | Second-line | | PI | Lopinavir/r | Potent, high barrier | Pill burden, GI side effects, drug interactions, requires boosting | Salvage/special populations | | PI | Atazanavir/r | Better tolerated than LPV/r | Still requires boosting, higher pill burden | Salvage/special populations | **Warning:** Efavirenz is no longer recommended as first-line due to CNS toxicity and teratogenicity; it is now reserved for second-line or resource-limited settings where INSTIs are unavailable. ### CD4 Count Consideration At CD4 = 350 cells/μL, this patient is at moderate immunosuppression but does NOT have severe immunosuppression (CD4 <50). Therefore: - No need for protease inhibitor-based regimen (reserved for CD4 <50 or treatment-experienced patients). - INSTI-based regimen is optimal and recommended by NACO, WHO, and IAS-USA guidelines. [cite:Harrison 21e Ch 197]