Pharmacokinetics of Once-Daily Boosted Elvitegravir When Administered in Combination With Acid-Reducing Agents

Background: Acid-reducing agents are commonly used co-medications by HIV-1-infected patients receiving antiretroviral treatment. The effects of various representative acid-reducing agents on the pharmacokinetics (PK) of boosted elvitegravir were evaluated by 1-way interaction in 4 studies. Methods: Healthy subjects received ritonavir-boosted elvitegravir (EVG/r; 50/100 mg QD) administered alone or with antacid simultaneously in Study 1, staggered (+/- 2 or +/- 4 hours) or with omeprazole in Study 2; Studies 3 and 4 evaluated cobicistat-boosted elvitegravir (EVG/co; 150/150 mg QD) administered simultaneously or staggered (+ 12 hours) with famotidine or omeprazole. Lack of PK alteration was defined as 90% confidence intervals about the geometric least squares means ratio (coadministration: alone) being within 70%-143% for elvitegravir C-max (maximum concentration), C-tau (trough), and AUC(tau) (area under plasma concentration-time curve; 0-24 hours); cobicistat PK were explored. Results: EVG exposures were 40%-50% lower upon simultaneous dosing of EVG/r and antacids, probably due to local complexation with cations in gastrointestinal tract, and were unaffected with >= 2 hours staggered dosing. No relevant drug interactions were observed between EVG/co and famotidine or between EVG/r or EVG/co and omeprazole, indicating the absence of a broader pH effect on boosted EVG PK. In all studies, study treatments were well tolerated, with adverse events being generally mild to moderate in severity and primarily gastrointestinal disorders. Conclusions: There are no clinically relevant interactions between boosted elvitegravir, and thus elvitegravir/cobicistat/emtricitabine/ tenofovir DF single-tablet regimen, and H2-receptor antagonists or proton pump inhibitors; staggered antacid administration by >= 2 hours is recommended.