IN-VITRO ACTIVITY OF INHIBITORS OF LATE STAGES OF THE REPLICATION OF HIV IN CHRONICALLY INFECTED MACROPHAGES

Because of the importance of macrophages in the pathogenesis of the di sease caused by HIV, we investigated the efficacy of various anti-HIV drugs in human primary macrophages acutely or chronically infected by this virus. The results obtained for acutely infected macrophages show that dideoxynucleosides (AZT, ddI, and ddC), interferon-alpha and -ga mma, mismatched double-stranded RNA, Tat inhibitor, phosphorothioate a ntisense, and inhibitors of HIV protease, all significantly inhibit vi rus replication at concentrations far below those toxic for the cells. However, in macrophages in which proviral DNA is already integrated ( chronically infected macrophages), only the three inhibitors of HIV pr otease induced significant virus inhibition at concentrations 100 or m ore times higher than those effective in acutely infected macrophages. Treatment of macrophages with macrophage colony-stimulating factor do es not affect the anti-HIV efficacy of protease inhibitors. These resu lts suggest that therapeutic strategies with activity for macrophages, including inhibitors of HIV protease, are worth pursuing in patients with HIV infection.