PT  - JOURNAL ARTICLE
AU  - P Harvie
AU  - R F Omar
AU  - N Dusserre
AU  - N Lansac
AU  - A Désormeaux
AU  - P Gourde
AU  - M Simard
AU  - M Tremblay
AU  - D Beauchamp
AU  - M G Bergeron
TI  - Ribavirin potentiates the efficacy and toxicity of 2',3'- dideoxyinosine in the murine acquired immunodeficiency syndrome model.
DP  - 1996 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1009--1017
VI  - 279
IP  - 2
4099  - http://jpet.aspetjournals.org/content/279/2/1009.short
4100  - http://jpet.aspetjournals.org/content/279/2/1009.full
SO  - J Pharmacol Exp Ther1996 Nov 01; 279
AB  - The efficacy and toxicity of ribavirin (25 or 125 mg/kg/day), 2',3'-dideoxyinosine (ddI) (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 protection against splenomegaly, lymphadenopathy and hypergammaglobulinemia in mice treated with ribavirin at 25 mg/kg/day alone or in combination with ddI at 200 mg/kg/day. A good synergistic effect was observed with the drug combination, whereas ddI alone (200 mg/kg/day) did not give any protection. Ribavirin/ddI combination protected against the loss of CD8 T cells in spleen and restored the capacity of splenocytes to proliferate after activation with a mitogenic agent. Moreover, the drug combination resulted in a protection of the spleen and cervical lymph node architectures and a regression of germinal centers. Hematotoxicity appeared at a dose of 125 mg/kg of ribavirin alone and increased when used concomitantly with ddI. In conclusion, ribavirin and ddI at low doses are synergistic and effective in the murine acquired immunodeficiency disease model, but at high doses they are toxic.