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Impact and differential clinical utility of cobicistat-boosted darunavir in HIV/AIDS

Authors Cossu MV, Astuti N, Capetti A, Rizzardini G

Received 28 February 2015

Accepted for publication 30 March 2015

Published 21 August 2015 Volume 2015:7 Pages 47—56

DOI https://doi.org/10.2147/VAAT.S83680

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Jonathan Dinman

Maria Vittoria Cossu, Noemi Astuti, Amedeo Capetti, Giuliano Rizzardini

1st Division of Infectious Diseases, Luigi Sacco University Hospital, Milan, Italy

Abstract: Cobicistat (Cobi) is a pharmacoenhancer, without anti-HIV activity, that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV). In particular, Cobi is a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, the main metabolizing pathway of this class of antiretrovirals. Due to its more selective inhibition of CYP3A, Cobi has a lower potential for off-target drug interactions than the standard boosting agent ritonavir (RTV), and lower likelihood for enzymatic induction. In pharmacokinetic studies of healthy volunteers, DRV boosted with Cobi attains plasma concentrations that are comparable to those achieved with 100 mg RTV as booster. In Phase III clinical trials, conducted in naïve subjects, the coformulation yielded high rates of suppression of viral replication, on average 82%–83% of treated patients reaching undetectable viremia after 48 weeks of therapy. The selection of resistance associated with mutations was a rare event and no phenotypic resistance to DRV emerged in viral failures. Generally, Cobi was well tolerated; however, it has been shown to decrease estimated creatinine clearance (ClCr) due to inhibition of tubular secretion of creatinine. Cobi, therefore, should not be initiated in patients with ClCr less than 70 mL/min, if any coadministered agent (eg, emtricitabine, lamivudine, tenofovir disoproxil fumarate, or adefovir) requires dose adjustment based on ClCr.DRV/Cobi fixed-dose combination is part of an important evolution of antiretroviral therapy toward simpler yet potent formulations. In this setting, it is important to combine potency, simplicity, safety, and high genetic barrier, as in this case.

Keywords: HIV, darunavir, Cobicistat, fixed dose, pharmacoenhancer

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