RIBAVIRIN POTENTIATES THE EFFICACY AND TOXICITY OF 2',3'-DIDEOXYINOSINE IN THE MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME MODEL

The efficacy and toxicity of ribavirin (25 or 125 mg/kg/day), 2',3'-di deoxyinosine (ddl) (200 mg/kg/day) and a combination of both drugs at these doses given for 6 weeks were investigated in the murine acquired immunodeficiency syndrome model. Our results showed a significant pro tection against splenomegaly, lymphadenopathy and hypergammaglobulinem ia in mice treated with ribavirin at 25 mg/kg/day alone or in combinat ion with ddl at 200 mg/kg/day. A good synergistic effect was observed with the drug combination, whereas ddl alone (200 mg/kg/day) did not g ive any protection. Ribavirin/ddl combination protected against the lo ss of CD8 T cells in spleen and restored the capacity of splenocytes t o proliferate after activation with a mitogenic agent. Moreover, the d rug combination resulted in a protection of the spleen and cervical ly mph node architectures and a regression of germinal centers. Hematotox icity appeared at a dose of 125 mg/kg of ribavirin alone and increased when used concomitantly with ddl. In conclusion, ribavirin and ddl at low doses are synergistic and effective in the murine acquired immuno deficiency disease model, but at high doses they are toxic.