Darunavir
💊 About
Darunavir is a modern protease inhibitor (PI) used as part of combination antiretroviral therapy (HAART or ART) for HIV-1 infection.
It has potent activity against many PI-resistant strains and is typically “boosted” with ritonavir or cobicistat to enhance bioavailability.
Always 🔗 check the BNF entry here for up-to-date dosing and cautions.
🧠 Mode of Action
- Darunavir inhibits the HIV-1 protease enzyme, blocking cleavage of gag-pol polyproteins into functional viral proteins.
- This results in immature, non-infectious viral particles incapable of replication.
- Its high binding affinity allows activity even against viruses resistant to older protease inhibitors.
📋 Indications & Dose
- Used in combination ART for treatment of HIV-1 infection in adults and children ≥3 years.
- Typical adult dose: 800 mg once daily with ritonavir 100 mg OD or cobicistat (boosted formulation).
- In treatment-experienced or resistant HIV, dosing may be 600 mg twice daily with ritonavir.
- Take with food to improve absorption and minimise GI effects.
⚠️ Interactions
- Extensively metabolised by CYP3A4; potent interactions with enzyme inducers (e.g. rifampicin, carbamazepine) or inhibitors.
- Ritonavir or cobicistat used for pharmacokinetic boosting also affect levels of other CYP3A4 substrates.
- Check all co-prescribed drugs carefully in the BNF before starting.
🚧 Cautions
- Use with caution in moderate hepatic impairment; avoid in severe hepatic disease.
- Monitor for metabolic effects — lipids, glucose, and weight gain.
- May cause skin rash or hypersensitivity (sulphonamide structure); avoid in known sulfa allergy if severe.
- Adherence is crucial — missed doses can promote resistance.
⛔ Contraindications
- Severe hepatic impairment.
- Co-administration with potent CYP3A4 inducers (e.g. rifampicin, St John’s wort) — reduces efficacy.
- Known hypersensitivity to darunavir or excipients.
💥 Side Effects
- 😣 Gastrointestinal disturbance (nausea, diarrhoea, abdominal pain).
- 📈 Metabolic effects: hyperlipidaemia, insulin resistance, lipodystrophy.
- 🌡️ Headache, fatigue, and rash.
- Rare: hepatic enzyme elevation, Stevens–Johnson syndrome, or hepatotoxicity.
📚 References
- BNF: Darunavir
- British HIV Association (BHIVA) Treatment Guidelines, 2023.
- European AIDS Clinical Society (EACS) Guidelines, 2023.
