FIV infection of macrophages: in vitro and in vivo inhibition by dideoxycytidine 5′-triphosphate

We have evaluated in vitro and in vivo whether it is possible to protect cat macrophages from feline immunodeficiency virus (FIV) infection by the administration of dideoxycytidine 5′-triphosphate (DDCTP). Since cell membranes are impermeable to phosphorylated drugs we have encapsulated DDCTP into autologous erythrocytes and modified erythrocyte membranes 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 treatment protected the majority of peritoneal macrophages during a 7 month experimental FIV infection and reduced the percentage of circulating lymphocytes stained with an anti-p24 antibody. These results suggest that the administration of nucleoside analogues in phosphorylated form is feasible and their targeting to macrophages reduces FIV infection in vitro and in vivo.