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

Better understanding of the pharmacokinetics of antiretroviral drugs has re sulted in the design of combination therapies for the treatment of human im munodeficiency virus (HIV) infection. This has improved the bioavailability and prolonged the plasma half-life of some of the drugs, resulting in enha nced antiviral activity. However, antiviral combination therapy can also re sult in adverse drug-drug interactions and diminished antiretroviral activi ty. 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 antivir al efficacy.