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ART (Antiretroviral Therapy) in HIV/AIDS — Complete Guide

Sources: Goldman-Cecil Medicine, Harrison's Principles of Internal Medicine 22E (2025), WHO Guidelines 2026, IAS-USA 2024, NIH Adult/Adolescent ARV Guidelines

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🔑 What is ART?

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🎯 Goals of ART

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✅ WHEN TO START ART

• Start as soon as possible after HIV diagnosis
• No threshold CD4 count required to initiate
• This was settled by the START trial (2015) and TEMPRANO trial (2015) — both showed clear benefit of early treatment even with CD4 >500 cells/μL
• In resource-limited settings (K Park/WHO context): same rule — treat all

Special situations: start ASAP (same day or within days)

• Pregnant women (prevents mother-to-child transmission)
• Patients with TB co-infection (special timing considerations — see below)
• Patients with cryptococcal meningitis (delay ART 4–6 weeks after starting antifungal)
• Patients hospitalized with severe opportunistic infections

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💊 DRUG CLASSES & MECHANISMS

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📋 KEY DRUGS BY CLASS

NRTIs (Backbone of most regimens)

NNRTIs

PIs (boosted with ritonavir or cobicistat)

INSTIs ⭐ (Currently Preferred Drugs)

Entry Inhibitors

Capsid Inhibitor (Newest)

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🏥 PREFERRED FIRST-LINE REGIMENS

For Most Adults (WHO 2026 / IAS-USA 2024 / NIH Guidelines)

• TDF + 3TC (or FTC) + DTG — preferred in LMICs (WHO)
• TAF/FTC + BIC (Biktarvy, 1 pill once daily) — preferred in high-income countries
• TAF/FTC + DTG (Triumeq/Dovato variant) — alternative preferred

• DTG + 3TC (Dovato) — only after HIV resistance & HBV testing known; VL any, CD4 any

In Pregnancy

• TDF or TAF + FTC + DTG or RAL (preferred)
• TDF + FTC + ATV/r or DRV/r (alternatives)
• Continue existing ART if already virologically suppressed
• DTG: rare neural tube defect risk at conception → counsel women of childbearing age

In TB Co-infection

• Start TB treatment first → start ART within 2–8 weeks (within 2 weeks if CD4 <50)
• Rifampicin induces CYP enzymes → use EFV-based regimen or DTG 50mg twice daily (not standard dose)
• Avoid PIs with rifampicin (rifampicin reduces PI levels dramatically)

In Cryptococcal Meningitis

• Delay ART 4–6 weeks after starting amphotericin B + fluconazole (immediate ART increases IRIS mortality)

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📊 MONITORING ON ART

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⚠️ VIROLOGIC FAILURE — WHAT TO DO

1. Assess adherence first (most common cause)
2. Review drug-drug interactions
3. Resistance testing (genotype) — guides switch
4. Design new regimen with ≥2 fully active drugs, at least one with high barrier to resistance (DTG or DRV/r)

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🚫 KEY DRUG-DRUG INTERACTIONS

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💉 LONG-ACTING (INJECTABLE) ART

• Adults/adolescents with adherence challenges to daily oral regimens
• Cabotegravir + rilpivirine (CAB/RPV) injected every 1–2 months
• Lenacapavir every 6 months (salvage, and emerging PrEP role)

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🧬 HIV CURE — CURRENT STATUS

• ART is not curative — HIV establishes a latent reservoir in CD4+ T cells that persists despite years of suppression
• Sterilizing cure (complete virus elimination): documented in ~4 cases via CCR5-deleted bone marrow transplants ("Berlin Patient," "London Patient," etc.)
• Functional cure: 14 patients treated during acute HIV kept viral suppression off ART — ongoing research
• CRISPR-Cas9 stem cell editing trials ongoing but not yet successful

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📌 K PARK / NATIONAL PROGRAM PERSPECTIVE

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🔄 SUMMARY: ART IN EASY STEPS

HIV diagnosed
     ↓
Start ART immediately (treat all)
     ↓
Choose regimen:
  → TDF + 3TC + DTG (WHO preferred / NACP India)
  → TAF/FTC + BIC (high-income setting)
     ↓
Monitor: Viral load at 4 wks, 3-6 monthly
     ↓
Goal: VL <200 (undetectable)
     ↓
If VL rises → check adherence → resistance test → switch regimen
     ↓
Continue lifelong

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📰 2024–2026 GUIDELINE UPDATES (New Highlights)

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