Comparative assessment of antiretrovirals in human monocyte-macrophages and lymphoid cell lines acutely and chronically infected with the human immunodeficiency virus

Abstract

We compared the efficacy of 3 antiretrovirals in cultured human peripheral blood monocyte-derived macrophages and lymphoid cells infected with the human immunodeficiency virus (HIV). Zidovudine (greater than 0.01 micrograms/ml) or foscarnet (greater than or equal to 100 micrograms/ml) consistently inhibited HIV replication (p24 antigen production) in acutely infected macrophages by more than 90%; alpha interferon (1,000 units/ml) inhibited HIV replication by 88-99%. Drug efficacy was equal in lymphoid cells and monocyte-derived macrophages. However, these antiretrovirals even in high concentration only minimally inhibited chronic, established HIV infection: while zidovudine (0.01 micrograms/ml) inhibited infection by over 90% in acutely infected macrophages and lymphoid cells, 50 micrograms/ml of this antiretroviral produced only 19-55% inhibition of HIV replication in chronically infected cells. Slot-blot analysis of HIV RNA was concordant with the p24 antigen data. Acutely infected macrophages are as susceptible to the inhibitory effects of antiretrovirals as lymphoid cells; however, chronically infected macrophages (which probably constitute the main in vivo reservoir for HIV) are several orders of magnitude more resistant.