Session 18Oral Abstract Presentations Viral Neuropathogenesis Session Day and Time: Wednesday 10 am - 12:30 pm Presentation Time: 12:00 Room: Ballroom C
94 Impaired Nerve Regeneration in HIV-associated Neuropathy M. J. Polydefkis*, P. Hauer, A. Brown, J. M. McArthur Johns Hopkins Univ Sch of Med, Baltimore, MD
Background: Loss of cutaneous innervation is a fundamental complication of HIV-associated sensory neuropathy (HIV-SN) that contributes to morbidity, limits antiviral therapy, and can compromise viral suppression. There is great interest in preventing or reversing the peripheral neuropathy associated with HIV infection through treatment with regenerative agents. To this end, we developed a model of experimental epidermal denervation that allows regenerative capacity to be systematically and efficiently measured.
Methods: Thirty-one (31) healthy volunteer subjects and 3 patients (pts) with HIV infection with normal distal thigh epidermal nerve fiber densities (ENFD) were enrolled. Capsaicin cream was applied topically to a demarcated normal area on the distal thigh resulting in a superficial denervation of the epidermis and dermis. Skin biopsies were obtained at baseline, immediately following denervation and then at multiple time points subsequently. Skin samples were processed to allow visualization and quantitation of the epidermal nerve fibers (ENF). A blinded technician determined the ENFD expressed as fibers per mm.
Results: Healthy controls and HIV pts had similar ages (37.5 + 11.5 vs 40.7 + 3.8 yrs) and gender distributions (58% vs 66% male). All HIV pts had a history of exposure to ddI or d4t. HIV pts had both signs and symptoms of neuropathy as determined by neurological examination, nerve conduction testing, and distal leg skin biopsy, while healthy controls had no evidence of neuropathy. Healthy volunteers regenerated ENF at a rate of 0.185 fibers/mm/day (95% CI: 0.15 – 0.21 fibers/mm/day), while the rate of nerve fiber regeneration was significantly decreased among HIV pts (0.048 fibers/mm/day, 95% CI: -0.148 - 0.111 fibers/mm/day, p < 0.001).
Conclusions: HIV pts with neuropathy have a decreased capacity for ENF regeneration after chemical axotomy compared to healthy controls. These results suggest that impaired nerve regeneration may play a role in the pathophysiology of HIV-SN. Measurement of ENF regeneration has the potential to be an efficient outcome measure in future trials of agents designed to promote regeneration in peripheral neuropathy.
