Darunavir: a second-generation protease inhibitor.

Area of Science:

• Pharmacology and Therapeutics
• Infectious Diseases
• Virology

Background:

• Darunavir is a novel protease inhibitor (PI) approved for human immunodeficiency virus (HIV) treatment.
• It exhibits unique activity against multidrug-resistant HIV strains, differentiating it from other PIs.
• Understanding its pharmacology, pharmacokinetics, and clinical profile is crucial for optimizing HIV therapy.

Purpose of the Study:

• To review the pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse events, and dosing of darunavir.
• To evaluate darunavir's place in therapy for HIV-infected patients, particularly those with prior antiretroviral exposure.
• To highlight darunavir's effectiveness against drug-resistant HIV strains.

Main Methods:

• Review of existing literature on darunavir's properties and clinical trials.
• Analysis of pharmacokinetic data, including absorption, bioavailability, protein binding, and metabolism.
• Evaluation of clinical trial results assessing viral load reduction and CD4+ T-cell count changes.

Main Results:

• Darunavir is well absorbed, with increased bioavailability when taken with food.
• It is metabolized by and inhibits CYP3A4, indicating potential for drug-drug interactions.
• Clinical trials demonstrated significant HIV RNA reduction (2 log(10) decrease) and CD4+ T-cell increases (124 cells/mm(3)) compared to controls.
• Adverse events were comparable to other PIs; recommended dosage is 600 mg darunavir with 100 mg ritonavir every 12 hours with food.

Conclusions:

• Darunavir is an effective new HIV PI with retained activity against protease mutations.
• It is a valuable option for optimized combination antiretroviral therapy in treatment-experienced patients.
• Caution is advised in patients with hepatic dysfunction; no dosage adjustment is needed for mild/moderate renal impairment.