A MULTICENTER PHASE I II DOSE-ESCALATION STUDY OF SINGLE-DOSE CIDOFOVIR GEL FOR TREATMENT OF RECURRENT GENITAL HERPES/

A randomized, double-blind, clinic-initiated, sequential dose-escalati on pilot study was performed to compare the safety and efficacy of sin gle applications of 1, 3, and 5% cidofovir gel with placebo in the tre atment of early, lesional, recurrent genital herpes at five Canadian o utpatient sites. Ninety-six patients began treatment within 12 h of le sion appearance and were evaluated twice daily until healing of the le sion occurred. Cidofovir gel at all: strengths significantly decreased the median time to negative virus culture in a dose-dependent fashion (3.0 days in the placebo group versus 2.2, 13, and 1.1 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively; P = 0.02, 0.0 001, and 0.0003, respectively). A trend toward a reduction in the medi an time to complete healing in association with treatment was present, but the differences were not statistically significant (5.0 days in t he placebo group versus 4.3, 4.1, and 4.6 days in the 1, 3, and 5% cid ofovir gel treatment groups, respectively). Application site reactions occurred in 3, 5, 19, and 22% of the patients in these four groups, r espectively. Treatment-associated lesion recrudescence with delayed he aling, which is suggestive of local toxicity, was observed in three pa tients treated with 5% cidofovir gel and one patient treated with 3% c idofovir gel. In summary, single-dose application of cidofovir gel con fers a significant antiviral effect on lesions of recurrent genital he rpes. Additional studies are warranted to further identify the optimal efficacious dose of cidofovir in association with the maximum gel str ength that can be tolerated.