A 32-year-old man with newly diagnosed HIV infection (CD4 count 180 cells/μL) and a positive tuberculin skin test presents with cough and fever. Chest X-ray shows upper lobe infiltrates consistent with tuberculosis. He has no prior antiretroviral therapy. What is the drug of choice for initiating antiretroviral therapy in this patient?

Explanation

## First-Line ART in TB-HIV Coinfection **Key Point:** In patients with TB-HIV coinfection, integrase inhibitor-based regimens (particularly dolutegravir) are now preferred over efavirenz-based regimens as first-line therapy. ### Rationale for Dolutegravir 1. **Minimal drug-drug interactions with rifampicin** — dolutegravir can be used at standard doses (50 mg twice daily) with rifampicin-containing TB regimens, whereas efavirenz requires dose adjustment and has suboptimal levels. 2. **Superior virological efficacy** — integrase inhibitors demonstrate faster viral suppression and better immunological recovery in TB-HIV coinfection. 3. **Better tolerability** — dolutegravir avoids the CNS side effects (dizziness, insomnia, nightmares) and teratogenicity concerns associated with efavirenz. 4. **WHO and Indian guidelines** — current recommendations (2023 onwards) prioritize dolutegravir-based regimens in TB-HIV coinfection, even at low CD4 counts. ### Why Not Other Options? | Regimen | Issue in TB-HIV | |---------|----------------| | **Efavirenz** | Significant drug-drug interaction with rifampicin; requires dose increase to 600 mg daily; suboptimal levels; CNS toxicity | | **Protease inhibitor (LPV/r)** | Severe interaction with rifampicin; requires dose increase to LPV/r 800/200 mg twice daily; hepatotoxicity risk | | **Nevirapine** | High risk of hepatotoxicity, especially at CD4 <50 cells/μL; drug interaction with rifampicin | **High-Yield:** Dolutegravir 50 mg BD (or 50 mg OD if given with rifampicin) + 2 NRTIs is the current gold standard for TB-HIV coinfection. **Clinical Pearl:** TB immune reconstitution inflammatory syndrome (TB-IRIS) is common when CD4 <50 cells/μL; integrase inhibitors allow rapid immune recovery, increasing IRIS risk but improving long-term outcomes. [cite:Harrison 21e Ch 197]