Darunavir: A Nonpeptidic Antiretroviral Protease Inhibitor

Background: Protease inhibitors were a major therapeutic breakthrough in the mid-1990s for the treatment of HIV infection, which resulted in improved life expectancy for patients who had failed previous therapies. With time and evolution of the virus, however, there is a new population of patients with treatment-resistant disease and few treatment options. Darunavir is a synthetic nonpeptidic analogue of amprenavir with enhanced activity against resistant virus that became available in 2006.Objectives: The purpose of this review was to describe the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, and clinical efficacy of darunavir. Also discussed are the published clinical experience with darunavir, its adverse events, drug interactions, pharmacoeconomics, and dosing and administration.Methods: A MEDLINE and EMBASE search (English-language only) was performed from January 1996 through April 2007 using the key words darunavir and TMC114. Abstracts from relevant scientific meetings were searched for the years 2000 through 2007. Additionally, the US Food and Drug Administration Web site was accessed to review the new drug application summary and data presented therein.Results: Darunavir was found to maintain antiretroviral activity against HIV with protease inhibitor mutations in 6 studies. Clinical efficacy and safety data are limited to 4 controlled and 2 uncontrolled trials. In 2 large Phase IIb clinical studies, viral suppression at 48 weeks to undetectable levels in heavily pretreated patients was achieved in 45% of patients compared with 10% of patients in the control group (P < 0.001). The addition of enfuvirtide enhanced this response rate to 58% compared with 11% of the patients who did not receive enfuvirtide (P < 0.001). Gastrointestinal symptoms, nausea, and headache were the most commonly reported events.Conclusions: Darunavir has improved activity against resistant HIV isolates in patients with few treatment choices, particularly when enfuvirtide is added. The safety profile of darunavir is comparable to other protease inhibitors based on early data. (Clin Ther. 2007;29:1559-1576) Copyright © 2007 Excerpta Medica, Inc.