ANTIVIRAL EFFICACY AND TOXICITY OF RIBAVIRIN IN MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME MODEL

The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosi ne analogue, have been evaluated in mice infected with the LP-BM5 viru s pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Dose s ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally t wice a day for 6 weeks to infected mice. Drug treatment induced a sign ificant protection against splenomegaly and lymphadenopathy at doses g reater than or equal to 25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of splee n CD8(+) T cells, and reconstituted the capacity of splenocytes to pro liferate in response to concanavalin A. The spleen and cervical lymph node architectures were protected, and a reduction in the emergence of germinal centers was observed at 50 mg/kg ribavirin. Hematotoxicity a ppeared at doses greater than or equal to 50 mg/kg ribavirin, and seve re anemia was predominant only at doses of 100 and 200 mg/kg. This stu dy shows that ribavirin protects mice against the effects resulting fr om retrovirus infection at doses of greater than or equal to 50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses greater th an or equal to 100 mg/kg.