Acid suppressive therapy and the effects on protease inhibitors

OBJECTIVE: To review the literature associated with the pharmacokinetic interaction between protease inhibitors (Pis) and acid suppressive therapies and to characterize the impact of this interaction on virologic and immunologic outcomes. DATA SOURCES: A MEDILINE search (1966-October 2006) was conducted using the names of the 10 Pis and specific acid suppressive therapies including antacids, histamine(2)-receptor antagonists, and proton pump inhibitors. Abstracts and poster presentations from recent HIV/AIDS meetings were reviewed for relevance. References from retrieved articles, as well as product packaging and manufacturer information, were evaluated. STUDY SELECTION AND DATA EXTRACTION: Pertinent pharmacokinetic, immunologic, and virologic studies, in healthy and HIVinfected patients, evaluating the use of a PI and acid suppressive therapy were reviewed. DATA SYNTHESIS: Potential interactions between concomitant acid suppressive therapy and Pis were evaluated. Available information indicates that indinavir and atazanavir require an acidic gastric medium for adequate absorption. Indinavir pharmacokinetic parameters are variable with acid suppressive therapy but primarily result in decreased oral absorption. This interaction abates with concurrent ritonavir use. No immunologic or virologic data are available regarding the concomitant use of indinavir and acid suppressive therapy. The minimum concentration of atazanavir, area under the concentration-time curve, and maximum concentration are significantly reduced when used concurrently with acid suppressive therapy. Atazanavir 300 or 400 mg boosted with ritonavir 100 mg increases plasma concentrations when used with acid suppressive drugs. Virologic and immunologic outcomes appear stable when boosted atazanavir is used in HIV-positive patients. Atazanavir therapeutic monitoring should be considered when used in combination with acid suppressive therapy. CONCLUSIONS: Of the Pis reviewed, significant pharmacokinetic interactions exist between acid suppressive therapy and indinavir or atazanavir. These Pis should be used with low-dose ritonavir if acid suppressive therapy is necessary.