FIV INFECTION OF MACROPHAGES - IN-VITRO AND IN-VIVO INHIBITION BY DIDEOXYCYTIDINE 5'-TRIPHOSPBATE

We have evaluated in vitro and in vivo whether it is possible to prote ct cat macrophages from feline immunodeficiency virus (FIV) infection by the administration of dideoxycytidine 5'-triphosphate (DDCTP). Sinc e cell membranes are impermeable to phosphorylated drugs we have encap sulated DDCTP into autologous erythrocytes and modified erythrocyte me mbranes to target these drug-loaded cells to macrophages. DDCTP-loaded erythrocytes reduced FIV production by macrophages infected in vitro or obtained from naturally or experimentally infected cats. The same t reatment protected the majority of peritoneal macrophages during a 7 m onth experimental FIV infection and reduced the percentage of circulat ing lymphocytes stained with an anti-p24 antibody. These results sugge st that the administration of nucleoside analogues in phosphorylated f arm is feasible and their targeting to macrophages reduces FIV infecti on in vitro and in vivo.