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 inhibitors was investigated in human primary monocytes/macrophages (M/M) chronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhibited 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 the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was similar to 7- to 26-fold lower than in acutely infected M/M and similar to 2- to 10-fold lower than in chronically infected H9 lymphocytes, When protease inhibitors were removed from cultures of chronically infected M/M, production of virus rapidly returned to the levels found in untreated MIM. Therefore, relatively high 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 drugs.