A 32-year-old man with newly diagnosed HIV-1 infection (CD4 count 180 cells/µL, viral load 150,000 copies/mL) presents to the antiretroviral clinic. He has no prior antiretroviral exposure. Physical examination reveals oral candidiasis and hepatomegaly. His baseline investigations show: ALT 95 U/L, AST 110 U/L, creatinine 0.9 mg/dL, HBsAg positive, anti-HCV negative. Which of the following is the most appropriate first-line antiretroviral regimen for this patient?

Explanation

## Clinical Context This patient presents with advanced HIV disease (CD4 < 200 cells/µL) and concurrent HBsAg positivity, which significantly influences antiretroviral selection. ## Key Point: **Integrase inhibitor (dolutegravir)-based regimen is preferred in advanced disease and HBV co-infection.** Tenofovir + Lamivudine + Dolutegravir is the current WHO and Indian national guideline recommendation for first-line therapy in treatment-naïve patients, especially with CD4 < 200 cells/µL. ## Why This Regimen? ### Tenofovir (TDF or TAF) - Nucleotide reverse transcriptase inhibitor (NtRTI) - Excellent HBV activity (critical in HBsAg+ patients) - Renal monitoring required; creatinine normal here - Superior to zidovudine in modern regimens ### Lamivudine (3TC) - Nucleoside reverse transcriptase inhibitor (NRTI) - Potent HBV suppression (prevents HBV flare on ART discontinuation) - Low barrier to resistance when used alone - Safe in advanced immunosuppression ### Dolutegravir (DTG) - Integrase strand transfer inhibitor (INSTI) - **Preferred over NNRTI (efavirenz) in CD4 < 200 cells/µL** — lower risk of immune reconstitution inflammatory syndrome (IRIS) - Superior virological potency and genetic barrier to resistance - Minimal hepatotoxicity (safe despite elevated transaminases) - No significant drug interactions with TB drugs (if TB develops) - Rapid viral suppression critical in advanced disease ## High-Yield: **In HBV/HIV co-infection, always use dual HBV-active agents (tenofovir + lamivudine or tenofovir + entecavir).** Lamivudine monotherapy leads to HBV resistance and flares. ## Clinical Pearl: **Efavirenz is contraindicated in CD4 < 200 cells/µL** due to higher IRIS risk and CNS toxicity in severe immunosuppression. Integrase inhibitors are preferred in this setting. ## Warning: **Do NOT use nevirapine in CD4 < 200 cells/µL** — severe hepatotoxicity and Stevens-Johnson syndrome risk, especially in HBsAg+ patients. ## Mnemonic: **TLD = Tenofovir + Lamivudine + Dolutegravir** — the modern preferred first-line regimen for treatment-naïve patients in resource-limited settings (WHO 2019 update). [cite:Harrison 21e Ch 197]