ANTI-HIV TYPE-1 ACTIVITY OF SULFATED DERIVATIVES OF DEXTRIN AGAINST PRIMARY VIRAL ISOLATES OF HIV TYPE-1 IN LYMPHOCYTES AND MONOCYTE-DERIVED MACROPHAGES

The anti-EW-l activity of sulfated derivatives of dextrin was tested i n activated peripheral blood mononuclear cells and in monocyte-derived macrophages using low-passage syncytium-inducing and non-syncytium-in ducing primary viral isolates of HIV-1. All four compounds blocked inf ection in a dose-dependent manner, Dextrin 2-sulfate blocked infection with a 90% inhibitory concentration (IC90) of 69 mu g ml(-1). The IC9 0 for dextrin 3-sulfate was 50 mu g ml(-1) and for dextrin 6-sulfate w as 14 mu g ml(-1). increasing the number of sulfate groups to three pe r glucan molecule (dextrin 2-, 3-, and 6-sulfate) did not reduce the I C90 further (13 mu g ml(-1)) compared to dextrin 6-sulfate, There was no significant difference in the concentration required to block infec tion of activated peripheral blood mononuclear cells when compared wit h monocyte derived macrophages, irrespective of whether low-passage sy ncytium-inducing or non-syncytium-inducing primary viral isolates of H IV-1 were used, Dextrin a-sulfate and dextrin 6-sulfate also reduced t he transmission of HIV-1 in experiments performed using peripheral blo od mononuclear cells from HIV-1-positive patients by 6- to 251-fold in a limiting dilution tissue culture infectious dose assay, Sulfated de xtrins were not toxic to either primary lymphocytes or macrophages at the concentrations tested, Having previously shown that the cell surfa ce binding of sulfated dextrins is dependent on the position of the ne gatively charged sulfate groups, we now show that their anti-HIV-1 act ivity in primary lymphocytes and macrophages is also dependent on the same arrangement, A phase Im clinical trial of dextrin 2-sulfate is no w in progress.