Antiretroviral Therapy Pharmacology
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Direct answer
India's national programme treats every adult and adolescent with HIV with a single fixed-dose tablet, TLD: tenofovir disoproxil fumarate 300 mg plus lamivudine 300 mg plus the integrase inhibitor dolutegravir 50 mg, once daily. Dolutegravir displaced efavirenz because of faster viral suppression, a high genetic barrier to resistance, and better tolerability — at the cost of some weight gain. Success is defined by a viral load below 50 copies per millilitre by six months; anything above 1000 copies triggers adherence counselling and resistance testing before any switch. Beyond the regimen itself, examinable applied points include cotrimoxazole prophylaxis at low CD4 counts, screening for tuberculosis before starting ART, and immune reconstitution inflammatory syndrome in the first weeks of therapy.
What you must remember
- TLD components: TDF 300 mg + 3TC 300 mg + dolutegravir 50 mg, one tablet daily — NACO's preferred first line for all adults and adolescents, including women of childbearing potential, adopted nationally from around 2020.
- Toxicity map: TDF — renal tubular toxicity and bone mineral loss; zidovudine (older regimens) — anaemia and lipodystrophy; efavirenz — neuropsychiatric effects and rash; dolutegravir — insomnia, weight gain.
- Viral load target: suppression below 50 copies/mL at six months; a repeat level above 1000 copies/mL after adherence support means resistance testing and second line.
- Second line: a boosted protease inhibitor — darunavir/ritonavir (or atazanavir/ritonavir) — plus two nucleoside analogues, guided by genotype where available.
- Cotrimoxazole prophylaxis: started at low CD4 counts (NACO has used a CD4 350 threshold; WHO endorses universal use in high TB-burden settings) and continued until immune recovery.
- TB first, then ART: active tuberculosis is treated first, with ART started within two weeks (earlier when CD4 is very low) — the leading cause of death in Indian PLHIV is TB, not HIV.
- PEP window: post-exposure prophylaxis within 72 hours for 28 days; perinatal and occupational protocols build on the same drugs.
- IRIS: paradoxical worsening of known (or unmasking of occult) opportunistic infection within weeks of ART — treat the infection, usually continue ART.
A typical programme patient, worked through
A 32-year-old man presents with dysphagia; endoscopy shows candida oesophagitis, and HIV serology is positive with CD4 90 cells/mm³. The sequence matters more than any single prescription. First, screen for tuberculosis — symptom screen, and if positive, sputum and chest imaging — because starting ART into undiagnosed TB invites disaster. Second, start cotrimoxazole prophylaxis: with a CD4 under 200 he qualifies regardless of symptoms. Third, start TLD once TB is excluded or covered; if TB is found, attention goes to interactions — rifampicin lowers dolutegravir levels, so the dolutegravir component is dosed twice daily, a detail programmes manage routinely.
Two weeks later he returns with new high fever and worsening chest findings. Before blaming drug failure, recognise immune reconstitution inflammatory syndrome: the recovering CD4 response is now visible against residual antigen. Management is to treat the opportunistic infection, give short steroids when indicated (for example, in paradoxical TB-IRIS), and almost always continue ART. At six months, his viral load — not his CD4 count — is the pass/fail test of the regimen; CD4 recovers slowly and imperfectly, but an undetectable viral load is the programme's definition of success.
How the exam frames it
NEET-PG frames ART pharmacology as three columns: drug, toxicity, and switch logic. Matching efavirenz with vivid dreams, zidovudine with anaemia, tenofovir with renal tubular damage, and dolutegravir with weight gain covers most one-liners. The Indian layer is programme knowledge: free ART through NACO centres since 2004, "test and treat" policy since 2017, and the national transition from efavirenz-based TLE to dolutegravir-based TLD — examiners like asking why the switch happened, and the answer (better tolerability, higher barrier to resistance, simpler once-daily tablet) is worth more than reciting the alphabet soup. The nevirapine-era question — rash and hepatotoxicity, historically restricted at high CD4 counts — still surfaces to test whether candidates understand why that drug left first line. One viva favourite: in a patient failing first line, you never change a single drug; you switch the whole regimen class after resistance assessment.
Frequently asked questions
What is the current first-line ART regimen in India?
TLD — tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and dolutegravir 50 mg as one fixed-dose tablet daily.
What viral load defines treatment success on ART?
Below 50 copies/mL by six months; a persistent level above 1000 copies/mL after counselling prompts resistance testing and regimen change.
What is IRIS and when does it occur?
Immune reconstitution inflammatory syndrome — paradoxical worsening or unmasking of opportunistic infections within weeks of starting ART as immunity recovers.
When should PEP be started after a needle-stick exposure?
Within 72 hours, taken for 28 days; the earlier the better, with TLD-based regimens now standard.
How is TB handled in a patient starting ART?
Treat TB first with antitubercular therapy, then start ART within two weeks, adjusting dolutegravir dosing for the rifampicin interaction.