INHIBITION OF MURINE AIDS BY COMBINATION OF AZT AND DIDEOXYCYTIDINE 5'-TRIPHOSPHATE

A combination of antiretroviral drugs acting on different cell types ( lymphocytes and macrophages) was evaluated in a murine retrovirus-indu ced immunodeficiency model of AIDS (MAIDS). In a first experiment, C57 BL/6 mice were infected with a single i.p. administration of LP-BM5 an d treated with 0.125 or 0.25 mg/ml AZT in drinking water for 3 months. AZT treatment was found to reduce lymphadenopathy (60 and 65%, respec tively), splenomegaly (37 and 50%, respectively), and hypergammaglobul inemia (6 and 50%, respectively). Furthermore, at the highest AZT conc entration, BM5d proviral DNA content in lymph nodes and in the spleen showed a reduction of 78 and 70%, respectively, compared to untreated animals. in a second experiment, infected mice were treated with AZT ( 0.25 mg/ml in drinking water) and with 2',3'-dideoxycytidine 5'-tripho sphate (ddCTP) encapsulated into autologous erythrocytes for macrophag e protection. Combined treatments resulted in a further reduction of l ymphadenopathy (a further 33% with respect to the single treatment of AZT) and splenomegaly (a further 28% respect to the single treatment o f AZT) but not of gammaglobulinemia. Proviral DNA in lymph nodes and s pleen showed a reduction of 82 and 77%, respectively, compared to infe cted mice. Stimulation index of T cells was also significantly increas ed in animals receiving both treatments versus AZT only. In conclusion , the selective administration of antiviral drugs that preferentially protect different cell types seems to provide additional advantages co mpared to single-agent therapy.