1987 – Zidovudine (AZT): The first licensed antiretroviral. Used as monotherapy, it produced short-term viral load reduction but rapid resistance due to HIV’s high replication and mutation rate.
Teaching point: monotherapy → resistance is inevitable in HIV.
Early–mid 1990s – Dual therapy: Two-drug NRTI regimens delayed progression but still failed long-term due to incomplete viral suppression.
Mid–late 1990s – HAART era: Combination therapy with 2 NRTIs + 1 PI or NNRTI (Highly Active Antiretroviral Therapy) achieved sustained viral suppression. This transformed HIV from a rapidly fatal disease into a chronic, manageable condition.
2000s – Adherence revolution: Fixed-dose combinations and once-daily regimens reduced pill burden, improving adherence and outcomes.
2010s–present – INSTI-based therapy: Integrase Strand Transfer Inhibitors (INSTIs) such as Dolutegravir, Bictegravir, Raltegravir became first-line due to:
- Rapid viral suppression
- Excellent tolerability
- High genetic barrier to resistance

💊 Preferred First-Line ART Regimens (UK / EACS / WHO)

Regimen Type	Examples & Notes
2 NRTIs + 1 INSTI (standard first-line)	TDF + FTC (or 3TC) + Dolutegravir Bictegravir/TDF/FTC (Biktarvy® – single tablet) Abacavir + 3TC + Dolutegravir (Triumeq®) Only if HLA-B5701 negative* Why INSTIs? Fast suppression, fewer interactions, better tolerated.
Alternative regimens	2 NRTIs + boosted PI (e.g. TDF/FTC + Atazanavir/r) Used if INSTIs contraindicated 2 NRTIs + NNRTI (Efavirenz, Rilpivirine) Less favoured due to neuropsychiatric effects & resistance
Special populations	Pregnancy: Current UK guidance supports Dolutegravir after the first trimester; Efavirenz has extensive safety data and remains acceptable. Renal impairment: Avoid TDF; consider Abacavir (if HLA-B*5701 negative) or TAF-based regimens.

⚠️ Key Practical Principles (Exam & Ward-Relevant)

Adherence is critical: Sustained viral suppression requires excellent adherence; poor adherence → resistance and treatment failure.
Monitoring:
- Viral load (expect undetectable within 3–6 months)
- CD4 count (immune recovery, OI risk)
- Toxicity: renal (TDF), hepatic, metabolic
Drug–drug interactions: PIs and NNRTIs induce or inhibit CYP450 → interactions with statins, DOACs, anticonvulsants, and transplant drugs.
PEP: TDF/FTC + Dolutegravir for 28 days after high-risk exposure.
PrEP: Daily TDF/FTC for HIV-negative individuals at ongoing risk.
OI prophylaxis: CD4 < 200 → co-trimoxazole for PCP until immune recovery.

📊 Monitoring Targets & Treatment Goals

Viral load: Undetectable within 24 weeks
CD4 recovery: ~100 cells/mm³ per year
Public health goal: U = U (Undetectable = Untransmittable)

🕒 When to Start ART (Modern Practice)

All patients with HIV should be offered ART regardless of CD4 count
Immediate initiation is essential in:
- AIDS-defining illness
- Pregnancy
- HIV nephropathy
- Hepatitis B co-infection

⚠️ Important Drug-Specific Adverse Effects

NRTIs: Lactic acidosis, neuropathy; AZT → bone marrow suppression
NNRTIs: Rash, hepatotoxicity, SJS/TEN (rare)
PIs: GI upset, dyslipidaemia, insulin resistance
Abacavir: Potentially fatal hypersensitivity – always check HLA-B*5701

📚 Key Guidelines

HIV Treatment Guidelines
Consolidated HIV Guidelines
Guidelines (2024)

The content on this website is provided for educational and informational purposes only to support exam preparation (e.g., MLA, MRCP, USMLE) and learning. This is NOT medical advice, diagnosis, treatment, or professional guidance. It does not replace consultation with a qualified healthcare professional, official guidelines (e.g., NICE, GMC, BNF), or supervised clinical practice. Always verify information with current, authoritative sources. Makindo and its contributors accept no liability for any reliance on this content, including errors, omissions, or any resulting harm, loss, or consequences. By using this site, you agree to these terms.

AIDS HAART Antiretroviral Drugs

📖 History of Antiretroviral Therapy (ART)