Effect of resiquimod 0.01% gel on lesion healing and viral shedding when applied to genital herpes lesions

Resiquimod, a Toll-like receptor 7/8 agonist developed as a topical treatment to decrease recurrences of anogenital herpes, induces proinflammatory cytokines that may delay lesion healing. Adults with frequently recurring anogenital herpes were randomized within 24 h of onset of a recurrence to vehicle or resiquimod 0.01% gel two times per week for 3 weeks. Subjects underwent daily lesion assessments and sampling for herpes simplex virus DNA PCR for 21 days or until investigator-determined healing of lesion(s). Eighty-two subjects with a mean age of 39 +/- 10.5 years and a median of seven recurrences per year were enrolled in the study. The qualifying recurrence was positive by PCR for herpes simplex virus in 68% of subjects. No difference was observed between the vehicle (39 subjects) and resiquimod (43 subjects) groups with respect to time to healing (median of 7.0 days versus median of 6.5 days, respectively; Cox proportional hazard model ratio of 1.229; 95% confidence interval, 0.778 to 1.942; P = 0.376). The distributions of maximum severity scores for any investigator-assessed local skin signs and for subject-assessed local symptoms were similar between treatment groups (P = 0.807 and P = 0.103, respectively). For subjects with at least one positive PCR result, no difference was observed for time to cessation of viral shedding (median of 7 days versus median of 5 days for vehicle and resiquimod groups, respectively; Cox proportional hazard model ratio of 1.471; 95% confidence interval, 0.786 to 2.754; P = 0.227). Application of resiquimod 0.01% two times per week for 3 weeks did not delay the healing of genital herpes lesions or reduce acute viral shedding.