Enhanced efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine in combination with gamma interferon against herpes simplex virus type 2 in mice

Abstract

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) and recombinant mouse interferon gamma (rMuIFN-gamma) were evaluated for their efficacy alone and in combination against a herpes simplex virus type 2 systemic infection in mice. Intraperitoneally infected animals were treated once a day with the drugs at various concentrations for 5 days starting 24 h after inoculation. DHPG was given subcutaneously and rMuIFN-gamma intraperitoneally. For DHPG, the effective dose at which 50% of the mice survived (ED50 was lowered approximately 10-fold from 3.4 to 0.25 mg/kg when given in combination with an ineffective dose of 4MuIFN-gamma (10(3) units per mouse). For rMuIFN-gamma, the ED50 was lowered greater than 10-fold from 6 x 10(3) to less than 3 x 10(2) units per mouse when given in combination with a marginally effective dose of DHPG (1 mg/kg). Construction of an isobologram and calculation of the corresponding fractional protective dose index (less than 0.12 where values less than or equal to 0.5 are considered synergistic) indicates an enhanced protective interaction by the combination of the two drugs.