Using pharmacokinetics to optimize antiretroviral drug-drug interactions in the treatment of human immunodeficiency virus infection.

Better understanding of the pharmacokinetics of antiretroviral drugs has resulted in the design of combination therapies for the treatment of human immunodeficiency virus (HIV) infection. This has improved the bioavailability and prolonged the plasma half-life of some of the drugs, resulting in enhanced antiviral activity. However, antiviral combination therapy can also result in adverse drug-drug interactions and diminished antiretroviral activity. In this review, we examine drug interactions involving combinations of protease inhibitors, combinations of protease inhibitors with nonnucleoside reverse transcriptase inhibitors, and combinations of nucleoside analogues for the treatment of patients with HIV infection. We discuss examples and mechanisms of pharmacokinetic interactions that improve or decrease antiviral efficacy.