Effects of therapy with an immunomodulator (imiquimod, R-837) alone and with acyclovir on genital HSV-2 infection in guinea-pigs when begun after lesion development.

We evaluated the effects of the immunomodulator, imiquimod (R-837) applied topically, alone and in combination with i.p. acyclovir (ACV) on acute, recurrent and neural HSV-2 genital infection in guinea-pigs when 10 days of therapy was begun after HSV lesions developed. The combined therapy was most effective, significantly reducing the severity of the acute disease, as early as 2 days (P < 0.05), and vaginal viral shedding (P < 0.05) as early as 1 day after therapy was begun. The total lesion score for the acute disease was also significantly less in the group receiving imiquimod and ACV (5.4 +/- 0.5) compared to controls (13.1 +/- 1.2, P < 0.001) or imiquimod alone (9.8 +/- 1.2, P < 0.05). Therapy, however, had no significant effect on the number of days with recurrent lesions. Imiquimod increased the lymphoproliferative response to HSV (P < 0.01), while combined therapy reduced HSV antibody titers (P < 0.01) on day 28 compared to placebo and also reduced the effect of imiquimod alone on the lymphoproliferative response. The combination of this effective immunomodulator, imiquimod, and acyclovir appears to provide effective therapy for acute genital HSV-2 infection even when begun after lesion development.