A new antiretroviral
drug (
azidothymidine homodinucleotide,
AZTp2AZT), designed for the protection of macrophages against retroviral
infection, was evaluated in a murine retrovirus-induced immunodeficiency model of
AIDS (
MAIDS) alone and in combination with oral
azidothymidine (AZT). C57BL/6 mice were infected with the retroviral complex LP-BM5 and treated for 3 months by weekly administrations of 15 nmol of
AZTp2AZT encapsulated into autologous erythrocytes for macrophage protection.
AZTp2AZT treatment was found to reduce lymphoadenopathy (48%),
splenomegaly (26%), and BM5d proviral
DNA content in lymph nodes, spleen, and brain of 37%, 40%, and 36%, respectively, compared with untreated animals. AZT administration in
drinking water (0.25 mg/ml) was more effective than administration of
AZTp2AZT encapsulated into erythrocytes in reducing lymphoadenopathy,
splenomegaly, gammaglobulinemia, and proviral
DNA content in lymph nodes, but it caused a reduction in erythrocyte count and hematocrit levels. Although combined treatments do not provide additive responses in the several parameters investigated, they were found to be much more effective in reducing the proviral
DNA content in brain (67%) than were monotherapies. Furthermore, no apparent signs of hematotoxicity were observed. Thus, macrophage delivery of
antiviral drugs may contribute to brain protection from retroviral
infections by mechanisms other than those exerted by oral AZT administration.