A simple method for investigating the antiviral activity of mixtures of two antiviral compounds against herpes simplex virus (HSV) is described; the technique involves a modification of the dye-uptake technique for measuring antiviral activity, and the results are analysed by two methods for evidence of synergy or additive or antagonist effects. The antiviral activity of combinations of four antiviral compounds against HSV-1 and HSV-2 were investigated. The results indicate that interferon-alpha (IFN-α) with acyclovir or ara-A shows synergy, but IFN-α with ribavirin shows an additive effect. Ribavirin shows no synergism with any of the three compounds tested, and ara-A shows marginal synergy with acyclovir. The pattern of these results does not allow any prediction of which mixtures may show synergy. With the present limited number of antiviral compounds, all new combinations should be tested; and these further results may allow future predictions.
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