Darunavir: a nonpeptidic protease inhibitor for antiretroviral-naive and treatment-experienced adults with HIV infection

Abstract

Introduction: Darunavir, a nonpeptidic inhibitor of the HIV-1 protease with potent activity against resistant virus, was initially approved by the FDA (2006) and the EMA (2007) for the treatment of antiretroviral-experienced adults, and later for naive adults. Darunavir/ritonavir (600/100 mg twice daily, ideally given with two other active antiretrovirals) demonstrated superior efficacy compared to lopinavir/ritonavir and other protease inhibitors in highly experienced patients. Darunavir/ritonavir (800/100 mg once daily) was demonstrated to be safe and effective for the treatment of naive patients and those with limited darunavir resistance-associated mutations (RAMs). Because darunavir must be coadministered with ritonavir, cytochrome P450 drug–drug interactions can be problematic.Areas covered: The chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety of darunavir are reviewed in this paper. A PubMed search was conducted using the search terms ‘randomized’, ‘darunavir’ and ‘efficacy’. Review articles and studies that primarily focused on other drugs were excluded.Expert opinion: Because darunavir exhibits efficacy against virus with significant protease inhibitor resistance mutations, it is critically important in the treatment of experienced patients, although viral suppression rates may be lower in those with a high baseline viral load or a greater number of cumulative darunavir RAMs. Darunavir/ritonavir is efficacious and well tolerated as a once-daily regimen in naive patients.