Antiviral Efficacy and Toxicity of Ribavirin in Murine Acquired Immunodeficiency Syndrome Model

The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected mice. Drug treatment induced a significant protection against splenomegaly and lymphadenopathy at doses > or = 25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of spleen CD8+ T cells, and reconstituted the capacity of splenocytes to proliferate 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 appeared at doses > or = 50 mg/kg ribavirin, and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study shows that ribavirin protects mice against the effects resulting from retrovirus infection at doses of > or = 50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses > or = 100 mg/kg.