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

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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 (>0.01 μg/ml) orfoscarnet (100 μg/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 μg/ml) inhibited infection by over 90% in acutely infected macrophages and lymphoid cells, 50 μg/ml of this antiretroviral produced only 19–55% inhibition of HIV 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.