Pharmacology · HIV protease inhibitors (PIs)
Darunavir !
A protease inhibitor with a high genetic barrier. Given boosted with ritonavir (or cobicistat) and with food; the preferred PI for second line.
Updated 2026-11-01
Also called: DRV
The figure shows darunavir in the active site of HIV-1 protease, between the two catalytic aspartic acids.
Mechanism of action
It binds tightly but reversibly to the active site of HIV aspartyl protease and also hinders the two halves from pairing into a dimer; the virus needs several mutations to resist it. Without active protease, the Gag and Gag-Pol polyproteins are not cut and virions come out immature.
- It binds the HIV protease active site
- Gag and Gag-Pol polyproteins stay uncut
- New virions come out immature and non-infectious
Pharmacokinetics
- Absorption
- Oral bioavailability 37% alone and 82% with ritonavir; taken with food
- Metabolism
- Liver, by CYP3A; ritonavir slows that metabolism
Indications
- HIV-1 infection, boosted and combined with other antiretrovirals HIV infection and AIDS →
Adverse effects
Common
- Diarrhoea, nausea, vomiting, abdominal pain
- Headache
- Rash
- Raised lipids
Contraindications
- Narrow-margin drugs highly dependent on CYP3A (for example simvastatin, lovastatin, certain sedatives and antiarrhythmics)
- Strong inducers such as rifampicin or St John's wort
Key interactions
- Rifampicin
- Greatly lowers darunavir: contraindicated
- Statins cleared by CYP3A
- Risk of myopathy and rhabdomyolysis
What is monitored
- Liver tests
- Lipids and glucose
- Skin
- Viral load and CD4
Administration and safety
- By mouth, with food and with its booster
- It has a sulfonamide group: ask about sulfa allergy
- Keep a full list of medicines and herbal products and review it with pharmacy before any new drug
Nursing care
- Confirm it is given with the ordered booster
- Teach to take it with food
- Watch for rash and signs of hepatitis
- Review interactions before any new drug
Pregnancy and breastfeeding
Antiretroviral treatment in pregnancy protects the mother and lowers HIV transmission to the baby; the treating team chooses the regimen.
Test yourself
Think of the answer, then tap the question to see it.
Why does darunavir withstand mutations better than other PIs?
It binds the active site very tightly and also prevents protease dimerisation; at least three associated mutations are needed to lose its effect.
What does ritonavir do to darunavir bioavailability?
It raises it greatly (from 37% to 82%) by inhibiting CYP3A metabolism.
Which chemical group in darunavir prompts an allergy question?
The sulfonamide: it is used with caution in sulfa allergy.
Related drugs
Related conditions
← Back to the class: HIV protease inhibitors (PIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - DARUNAVIR tablet, film coated (DailyMed (U.S. National Library of Medicine), 2025); Darunavir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.