Drug Interactions between HIV Protease Inhibitors and Acid-Reducing Agents

Maximal efficacy of protease inhibitor-based antiretroviral therapy for HIV/AIDS requires adequate drug absorption and bioavailability. However, the use of acid-reducing agents in patients treated with highly active antiretroviral therapy is common and may induce clinically significant drug-drug interactions that alter plasma protease inhibitor concentrations, which may lead to inadequate viral suppression or adverse events. As plasma antiretroviral concentrations are not routinely monitored in patients, it is important to understand the risk of these interactions and counsel patients appropriately, thereby maximizing antiviral potential and preventing the development of antiretroviral resistance. We therefore reviewed the literature to assess the current understanding of the effect of various acid-reducing agents on the pharmacokinetics of protease inhibitors.

The bioavailability of fosamprenavir, indinavir, lopinavir, nelfinavir and tipranavir has been reported to be negatively affected to varying degrees by certain acid-reducing agents. The negative effect on atazanavir concentrations observed in healthy subjects was more attenuated in HIV-infected patients and warrants further investigation. While the plasma concentration of saquinavir increased, short-term studies in healthy subjects did not indicate an increased risk of adverse events. No clinically relevant changes in plasma concentrations of darunavir occurred when combined with acid-reducing agents. The individual effect of acid-reducing agents on protease inhibitor concentrations is difficult to predict because of the large interpatient variability of plasma concentrations with some protease inhibitors. Studies suggest that some of the interactions between protease inhibitors and acid-reducing agents may be mitigated by temporal separation of dose administration. Educating patients about the importance of reporting the use of any acid-reducing agents, whether prescription or over-the-counter, is essential to optimizing the treatment of HIV disease, as is the need for care providers and patients to agree upon strategies for managing gastric symptoms and HIV disease simultaneously. Clinicians should be aware of the potential drug-drug interactions between some protease inhibitors and acid-reducing agents.