Efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine against primary and recrudescent genital herpes simplex virus type 2 infections in guinea pigs

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Abstract
The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) was evaluated for its efficacy in protecting guinea pigs from primary and recrudescent infections of herpes simplex virus type 2. Vaginally infected guinea pigs were treated twice a day with DHPG at 25 mg/kg per dose for 3 weeks. Subcutaneous doses were started 3 h, 24 h, or 5 weeks after virus inoculation. Treatment starting at 3 or 24 h reduced the severity of the primary infection by greater than 70% when lesions were graded for 3 weeks; lesion duration was lessened by greater than 55%. For 6 weeks after treatment, the number of recrudescent lesions was reduced by greater than 60%, and the duration of the recrudescences declined by greater than 40%. When dosing was started at 3 h postinfection, 33% of the animals did not develop any sign of primary or recrudescent infection throughout the 9-week test. By comparison, all the animals treated with DHPG starting at 24 h or with saline became infected. A 3-week DHPG regimen starting 5 weeks postinfection reduced the number of animals that developed recrudescent lesions by 70%. When treatment ended, however, recrudescent episodes in the animals increased to the level of saline-treated controls.These results suggest that (i) DHPG is highly effective in reducing the severity of both primary and recrudescent lesions of herpes simplex virus type 2, (ii) early treatment of a primary infection or treatment of recrudescences reduces the incidence of recrudescences, and (iii) the drug appears to have no effect on the latent form of the virus, as the incidence of recrudescences increases when DHPG treatment is ended.