RELATIVE POTENCY OF PROTEASE INHIBITORS IN MONOCYTES MACROPHAGES ACUTELY AND CHRONICALLY INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS/

The activity of three human immunodeficiency virus (HIV) protease inhi bitors was investigated in human primary monocytes/macrophages (M/M) c hronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhib ited the replication of HIV-1 in vitro, with EC(50)s of similar to 0.5 -3.3 mu M. However, only partial inhibition was achievable, even at th e highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was similar to 7- to 26-fold lower than in ac utely infected M/M and similar to 2- to 10-fold lower than in chronica lly infected H9 lymphocytes, When protease inhibitors were removed fro m cultures of chronically infected M/M, production of virus rapidly re turned to the levels found in untreated MIM. Therefore, relatively hig h concentrations of protease inhibitors are required to suppress HIV-1 production in chronically infected macrophages, and such cells may be a vulnerable point for the escape of virus in patients taking these d rugs.