HIV protease inhibitors: drug interactions

Introduction. - Management of HIV infection considerably improved over the past few years. Factors that contributed to this improvement are the follow ing: better knowledge of the dynamics of viral replication and immune respo nse, plasma viral load quantitation, use of new combinations with more pote nt antiretroviral drugs, simultaneous progress in treatment of opportunisti c infections. As a result, potential for drug interactions increased. Current knowledge and key points. - Due to changes in hepatic metabolism, p rotease inhibitors may interact with concurrent treatment. The most relevan t known drug interactions with each of the protease inhibitor (saquinavir. indinavir, ritonavir and nelfinavir) are summarized. Due to toxicity risks, co-administration is contraindicated for various interacting drugs, wherea s dosage adjustments may only be required for others. Such interactions hav e relevant consequences in clinical practice for the choice of the combinat ion that should be prescribed. However, they may have direct therapeutical benefit to the patient, particularly in the case of protease inhibitors. Future prospects and projects, - Though potential drug interactions require careful monitoring in clinical practice, they should not limit the use and therefore therapeutical benefit conferred by these highly active drugs. To better define the value of combinations of protease inhibitors and treatme nt with non-nucleosidic reverse transcriptase inhibitor further studies are required. As the number of drugs increases, experience and clinical practi ce in treatment of HIV infection will allow better knowledge of drug intera ctions and thereby optimal management of HIV-infected individuals. (C) 1999 Elsevier, Paris.