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Background:  Peripheral neuropathies are a frequent complication of long-standing HIV infection and can develop as a consequence of exposure to antiretroviral agents such as didanosine, stavudine, and zalcitabine. Pain is a predominant symptom and is described as burning that begins in the feet, often accompanied by numbness and paresthesias. Patients often times have neuropathic symptoms that persist for several months to years despite having been taken off these medications. This study was done to analyze dideoxynucleoside drug use along with certain variables that could potentially lead to persistent abnormal epidermal nerve fiber changes.    

Methods:  This was a retrospective analysis of the Nerve Project, a prospective cohort study of HIV-seropositive individuals with and without a clinical history of peripheral neuropathy. Of the 80 patients enrolled in the Nerve Project, 36 had skin biopsies available at the proximal thigh, and 37 at the distal leg. Epidermal nerve fiber density was at baseline and 48 weeks; 82% of subjects had dideoxynucleoside exposure. All subjects had CD4 cell count and HIV RNA viral load at their initial visit, along with other variables that contribute to neuropathy.

Results:  The analysis included 37 subjects:  79% were males, 21% females; 79% African American, 18.4% Caucasian, and 2.6% Hispanic; median CD4 was 259/ mm³, and HIV RNA viral load log₁₀ copies/mL was 3.6; 50% had never used alcohol socially, while 32% had abused it. Injection drug use (IDU) history was noted in 58%; 18% had used within 3 years of their first study visit, and 40% more than 3 years of the first study visit. Average epidermal nerve fiber density at the proximal thigh was 10.05/mm, and 5.45/mm at the distal leg. With respect to independent variables, the only statistically significant correlation was between CD4 cell count and proximal thigh epidermal nerve fiber densities (p = 0.006). No association was found between epidermal nerve fiber density and alcohol or IDU.

Conclusions:  Too few skin biopsies were taken to make a valid statistical correlation, but performed at 48 weeks may be a better correlate of dideoxynucleoside use and epidermal nerve fiber density. A statistically significant correlation was found between CD4 cell count and proximal thigh epidermal nerve fiber density. No statistically significant associations can be made between alcohol or IDU and epidermal nerve fiber density at the distal leg and proximal thigh.

Keywords: toxic neuropathy; hiv neuropathy; epidermal nerve fiber densities