Makindo Medical Notes

💊 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.