Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and recombinant human beta interferon alone and in combination on simian varicella virus infection in monkeys

Treatment of viral infections with combinations of antiviral agents may permit administration of reduced doses of either or both drugs. Lowered doses may reduce associated toxicity. Intravenous administration of substantial doses of either human recombinant beta interferon (rHuIFN-beta) or 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) prevents development of simian varicella virus infection in African green monkeys. Daily doses of 2 X 10(6) U of rHuIFN-beta/kg inhibited clinical disease in monkeys inoculated with simian varicella virus, and doses of DHPG between 20 and 60 mg/kg per day were necessary for similar antiviral effects. Intravenous administration of combinations of rHuIFN-beta and DHPG permitted an approximately 100-fold reduction in the effective dose of rHuIFN-beta and a 10-fold reduction in the effective dose of DHPG. Analysis of data relating to viremia by using the method of the median-effect principle showed the combination of rHuIFN-beta and DHPG was strongly synergistic in treatment of this infection.