The purpose of this study is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir, and elvitegravir (both in phase III drug development).
Data from January 2011 to April 2012 were evaluated. These data better characterized integrase inhibitor pharmacokinetics, assessed dosing regimens, and investigated previously undescribed drug–drug interactions. Due to formulation challenges, raltegravir inter-patient and intra-patient pharmacokinetic variability is high. Twice-daily 400 mg dosing has been shown to be clinically superior to 800 mg once-daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was US Food and Drug Administration (US FDA)-approved in December 2011. Cobicistat-boosted elvitegravir, and the second-generation integrase inhibitor dolutegravir, have lower pharmacokinetic variability and are dosed once daily. Dolutegravir drug interactions are similar to raltegravir, whereas boosted elvitegravir participates in additional CYP3A-mediated interactions.
Raltegravir's potent antiretroviral activity has resulted in widespread use in both treatment-naïve and experienced patients. Dolutegravir and cobicistat-boosted elvitegravir have some pharmacokinetic advantages. Pharmacokinetic data in special populations (pregnancy, pediatrics) to optimize dosing are still required.
aDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
bUniversity of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Correspondence to Angela D.M. Kashuba, BScPhm, PharmD, DABCP, Professor and Vice-Chair, Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, Director, UNC Center for AIDS Research Clinical Pharmacology and Analytical Chemistry Core, University of North Carolina at Chapel Hill, NC, USA. Tel: +1 919 966 9998; fax: +1 919 962 0644; e-mail: email@example.com