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Objectives Distal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre-existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV-infected Thai individuals naive to ARV therapy. Methods Distal leg and proximal thigh ENFDs were quantified in HIV-infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8-oxo-deoxyguanine (8-oxo-dG) break frequencies. Results In 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2–26.6) for the distal leg and 31.7 (26.2–40.0) for the proximal thigh. By linear regression, lower CD4 count (P

Objectives—Antiretroviral Toxic Neuropathy is associated with dideoxy-nucleoside reverse transcriptase inhibitor use in HIV, possibly due to mitochondrial toxicity. Acetyl-L-Carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate change in intra-epidermal nerve fiber (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000mg ALC daily. Methods—Punch skin biopsies were examined at baseline and 24 weeks after therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed. Results—Twenty-one subjects completed the study. ALC was generally well-tolerated. The IENF density did not change among cases completing 24 weeks of ALC therapy, with median (90% confidence interval (CI)) IENF changes of −1.70 (−3.50, ∞), p=0.98 and 2.15 (−0.10, ∞), p=0.11 for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (p