Safety of pharmacoenhancers for HIV therapy

HIV protease inhibitors have been part of highly active therapy regimens throughout the past 16 years of antiretroviral therapy. The majority of currently available protease inhibitors are coadministered with low-dose ritonavir (RTV) as a pharmacoenhancer, significantly increasing their plasma concentrations. This therapeutic principle called 'boosting' helped to overcome the obstacles of this class of drugs concerning unfavorable pharmacokinetics, resulting in either a high frequency of dosing or subtherapeutic plasma concentrations. The coadministration of RTV together with HIV protease inhibitors created a potent, clinically effective antiretroviral therapy, which is more convenient for the patient, and has revealed a high genetic barrier to viral resistance. RTV is the only pharmacoenhancing agent available to date; however, cobicistat, a selective CYP3A4 inhibitor, is about to enter the market. This article reviews current literature, compares the safety of both pharmacoenhancers and appraises their use in current and future HIV therapy.