Background:  Capsaicin activates the vanilloid receptor in cutaneous nerve fibers resulting in a burning sensation followed by functional nociceptor inactivation. Efficacy of low-dose topical capsaicin requires frequent dosing. In an open-label pilot study, a single high-concentration capsaicin dermal patch application (CDP; capsaicin 640 µg/cm² or 8% by weight) for 60 minutes yielded notable pain decreases in HIV-associated distal sensory polyneuropathy (HIV DSP) for 12 weeks. We now report the results of a randomized double-blind controlled trial evaluating the efficacy and safety of CDP in painful HIV DSP.

Methods:  This double-blind, multicenter study randomized 307 subjects with HIV DSP painful symptoms ≥ 2 months, stratified by neurotoxic antiretroviral status, to CDP or low-concentration capsaicin patch (control; capsaicin, 3.2 µg/cm² or 0.04% by weight) for 90, 60, or 30 minutes. Patches were applied to painful feet areas after a 60-minute topical anesthetic application. Subjects recorded daily pain intensity on an 11-point numeric pain rating scale (0 = no pain, 10 = worst possible pain). The primary efficacy endpoint was the percent change from baseline in mean “average pain for past 24 hours” scores for weeks 2 to 12.

Results:  The pooled CDP groups had a pain reduction of 23% during weeks 2 to 12 (from baseline of 5.9 to 4.7) compared with 11% (5.9 to 5.3) in the pooled control group (p = 0.0025). CDP 90-, 60-, and 30-minute groups reported 25%, 16%, and 28% reduction during weeks 2 to 12 (p = 0.0046, 0.287, and 0.0007, respectively). One third of all CDP, 36% of CDP 90-minute and 42% of CDP 30-minute subjects had ≥ 30% pain decrease from baseline during weeks 2 to 12, compared with 18% in the pooled control group (p ≤ 0.01). During weeks 2 through 12, weekly average pain decreases in the 90- and 30-minute CDP groups were stable and statistically significantly different from control. CDP groups also had significant improvement at week 12 compared to control for Patient Global Impression of Change, Gracely Pain Scale and Short-Form McGill Pain Questionnaire–Sensory Scores (all p ≤0.05). Despite transient pain increases due to CDP application, tolerability was good. Most treatment-related adverse events were mild to moderate local reactions that resolved quickly.

Conclusions:  This controlled trial in painful HIV DSP shows that CDP produces significant and durable pain reduction with good tolerability. CDP may provide a new mode of effective treatment for this disabling disease.