Development of topical thalidomide for aphthous ulcers of HIV/AIDS patients

Patients with HIV infection may experience large, painful oral aphthous ulcers which interfere with eating and speaking. Limited treatment options are available for these lesions in this patient population. Thalidomide given orally is effective, but use has been limited by a spectrum of adverse effects. This study tested the hypothesis that low dose topical administration would produce local tissue concentrations sufficient to promote ulcer healing without dose-limiting adverse effects.; Subjects were randomly assigned to receive 0 (placebo vehicle), 5, 10, or 20 mg of thalidomide ointment using a double-blind, randomized, placebo-controlled design. The primary endpoint of healing was defined as an 80 percent decrease from baseline size using methodology developed by NIAID's AIDS Clinical Trial Group. Blood samples were obtained 5 minutes prior to ointment placement (baseline), and at 5 minutes, 1, 2, and 4 hours after placement. Plasma was stored at −80°C until batched analysis for thalidomide by HPLC with UV detection on blinded, coded samples.; Patients enrolling into the study were primarily long-term survivors using combination therapy for the management of HIV disease. Probability of ulcer healing was highest for the 20 mg dose (87.5 percent), and a positive trend for dose response was observed. The mean time to ulcer healing was 17 days for the 20 mg group versus 23 days for those healing in the placebo group, and there were more unhealed ulcers (60 percent) in the placebo group compared to the other groups. A dose response pattern was also observed for pain relief, with the most significant reduction observed for the 20 mg dose. Adverse events were similarly distributed between treated and placebo groups and no subjects discontinued the study medication secondary to adverse effects, nor were any dose reductions necessary. Drug concentrations for the placebo, 5, and 10 mg doses were either undetectable or below the level of quantification, while the 20 mg dose was detectable at 5 minutes post-application, highest at 1 hour post-application, and decreased, but remained detectable at a little over 0.1 mg/mL over the course of the remaining observation period of four hours.; This dose-finding study represents the first report of tolerability and effectiveness of topical thalidomide. Topical thalidomide may be an effective alternative to PO thalidomide treatment for aphthous ulcers in patients with HIV infection, without the side effect liability.