Low-dose Oral Thimerosal for the Treatment of Oral Herpes: Clinical Trial Results and Improved Outcome After Post-hoc Analysis

Background: Thimerosal (TML) is an organomercury antimicrobial. Low doses (1/250^th of the amount in a typical vaccine dose) may promote an antiviral immune response. Low-dose TML (BTL-TML) was evaluated for safety and efficacy against herpes labialis in two FDA-approved, randomized, double blind, placebo-controlled clinical trials.

Methods: BTL-TML was evaluated in a Phase IIa trial for its ability to block progression to lesion in subjects with recurrent oral herpes caused by dental trauma. Subjects were administered BTL-TML or a saline control over a 7-day period. In a Phase IIb trial, BTL-TML was evaluated for its ability to block progression to lesion over a 7-day period in subjects with herpes lip infections induced by exposure to ultraviolet (UV) radiation.

Results: Progression to lesion post-dental procedure was prevented in 54.5% (12/22) TML subjects versus 22.2% (2/9) control subjects (p = 0.106). Progression to lesion post-UV irradiation was blocked in 47.8% (11/23) BTL-TML treatment subjects and 42.8% (6/14) control subjects. A post-hoc analysis yielded 52.2% (12/23) BTL-TML subjects with no progression to lesion versus 28.6% (6/21) control subjects with no progression (p = 0.099). There were no significant differences in adverse effects between treatment and control groups in either trial.

Conclusions: Neither clinical trial showed a statistically significant effect of BTL-TML on progression to lesion. However, the post-hoc analysis suggested there is a 48-hour period following UV radiation exposure during which the anti-herpes activity of antivirals such as BTL-TML is reduced. Accordingly, BTL-TML may have promise in subsequent, properly designed and powered clinical trials.