Darunavir

• HIV-1 Infection
• Antiretroviral Therapy
• Treatment-Experienced HIV
• Protease Inhibitor-Based Regimens

Darunavir is a protease inhibitor (PI) antiretroviral medication used in the treatment of HIV-1 infection. This second-generation protease inhibitor offers high potency, a favorable resistance profile, and is a key component of many preferred HIV treatment regimens when combined with a pharmacokinetic booster.

Mechanism of Action

Darunavir inhibits the HIV-1 protease enzyme, which is essential for cleaving the viral Gag-Pol polyprotein into individual functional proteins required for viral maturation. By binding to the active site of HIV protease with high affinity, darunavir prevents the production of mature, infectious viral particles. Newly produced virions remain non-infectious. Darunavir has a flexible molecular structure allowing it to adapt to protease mutations, contributing to its activity against many PI-resistant HIV strains. However, it must be co-administered with a pharmacokinetic enhancer (ritonavir or cobicistat) to achieve adequate plasma levels.

Available Formulations

Darunavir is available as tablets (75 mg, 150 mg, 600 mg, 800 mg) and oral suspension (100 mg/mL). It is also available in fixed-dose combination tablets with cobicistat (darunavir 800 mg/cobicistat 150 mg) and with cobicistat, emtricitabine, and tenofovir alafenamide as a complete single-tablet regimen. All formulations must be taken with food to ensure adequate absorption.

Medical Uses

Darunavir is FDA-approved for the treatment of HIV-1 infection in adults and pediatric patients 3 years of age and older, weighing at least 10 kg. It must be co-administered with ritonavir or cobicistat as a pharmacokinetic enhancer. Darunavir is used both in treatment-naive patients and in treatment-experienced patients with HIV strains resistant to other protease inhibitors. It is included in several guideline-recommended initial regimens, particularly for patients with high viral loads.

Dosing Guidelines

For treatment-naive or treatment-experienced patients with no darunavir resistance mutations, darunavir 800 mg plus ritonavir 100 mg (or cobicistat 150 mg) once daily with food is recommended. For treatment-experienced patients with one or more darunavir resistance mutations, darunavir 600 mg plus ritonavir 100 mg twice daily with food is used. Pediatric dosing is weight-based. The medication must always be taken with food and with a pharmacokinetic booster. Fixed-dose combinations simplify dosing.

Important Safety Information

Darunavir contains a sulfonamide moiety; use with caution in patients with sulfa allergy, though cross-reactivity is not well established. Hepatotoxicity, including acute hepatitis and hepatic decompensation, has been reported, particularly in patients with pre-existing liver disease or hepatitis coinfection. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred. New onset or worsening diabetes mellitus and diabetic ketoacidosis have been reported. Drug interactions through CYP3A4 are extensive and must be carefully evaluated.

Drug Interactions

Darunavir is a CYP3A inhibitor and substrate; ritonavir and cobicistat further inhibit CYP3A. Many drugs are contraindicated or require dose adjustment. Contraindicated drugs include alfuzosin, dronedarone, rifampin, ranolazine, certain anticonvulsants (with cobicistat), ergot derivatives, triazolam, oral midazolam, lovastatin, simvastatin, St. John's Wort, and sildenafil (for pulmonary hypertension). Many other medications require monitoring or dose adjustment. Always check for interactions before prescribing.

Special Populations

The Antiretroviral Pregnancy Registry monitors outcomes in pregnant women. Darunavir/ritonavir can be used during pregnancy with appropriate dosing. Once-daily dosing may not be appropriate during pregnancy due to pharmacokinetic changes. Breastfeeding is not recommended in HIV-infected women in resource-rich settings to prevent HIV transmission. Safety and efficacy have been established in pediatric patients 3 years and older. Elderly patients should be monitored for hepatic function. No dose adjustment is needed for renal impairment. Use with caution in hepatic impairment; darunavir is contraindicated in severe hepatic impairment.