Use of proteinase inhibitors in clinical practice

Drugs that are currently available for the treatment of human immunodeficiency virus (HIV) infection, the nucleoside analogs, are limited in their usefulness both by the fact that they all act at the same site of virus replication and because of the development of drug resistance. One of the major areas of HIV research therefore has been the development of new drugs, with the proteinase inhibitors showing promise in clinical trials. Proteinase inhibitors act at a different stage in the virus life cycle and are relatively nontoxic. Saquinavir mesylate (Hoffmann-La Roche, Nutley, NJ) is the most extensively tested and appears to have activity, as assessed by immunologic and virologic methods in small trials and in one AIDS Clinical Trials Group study. Continuing research in phase 3 studies will help to clarify the most appropriate use for this drug.