ANTIVIRAL EFFICACY AND TOXICITY OF RIBAVIRIN AND FOSCARNET EACH GIVENALONE OR IN COMBINATION IN THE MURINE AIDS MODEL

The antiviral efficacy and toxicity of ribavirin, foscarnet (PFA), and combinations of both drugs at two different doses have been evaluated in the murine AIDS (MAIDS) model, Our results clearly demonstrated th at infected mice treated with ribavirin at 100 mg/kg/day were protecte d against splenomegaly, lymphadenopathy, and hypergammaglobulinemia wh ereas PFA alone at 180 or 360 mg/kg/day did not afford any protection. Treatment with drug combinations showed protective effects similar to those observed with ribavirin alone. Hyperplasia and deorganization o f the lymphoid architecture were noted in spleen and lymph nodes of in fected mice compared to those of the uninfected group. However, treatm ent with ribavirin restored the lymphoid tissue architecture and reduc ed the emergence of germinal centers. Electron microscopic examination of renal cortex of animals treated with PFA at 360 mg/kg/day revealed clear mitochondrial necrosis (bursting of mitochondria) of the distal tubules and vacuolization of the proximal tubules which was more stri king with combination therapy. Regarding hematotoxicity, PFA did not c ause significant hematotoxicity at both doses, whereas ribavirin was h ematotoxic at both doses (50 and 100 mg/kg/day), this toxicity being m ore evident at the higher dose. In conclusion, treatment with ribaviri n showed clear efficacy against MAIDS whereas PFA had no efficacy. Fur thermore, ribavirin treatment caused hematoxicity and PEA treatment re sulted in nephrotoxicity. (C) 1997 Academic Press.