Determinants of epidermal nerve fibre density in antiretroviral‐naïve HIV‐infected individuals

• Published in: HIV medicine 2012-11, Vol.13 (10), p.602-608
• Main Authors: Shikuma, CM, Gerschenson, M, Ananworanich, J, Valcour, VG, Teeratakulpisarn, N, Jadwattanakul, T, DeGruttola, V, Liang, C‐Y, McArthur, JC, Ebenezer, GJ, Chomchey, N, Praihirunkit, P, Hongchookiath, P, Mathajittiphun, P, Nakamoto, B, Hauer, P, Phanuphak, P, Phanuphak, N
• Format: Article
• Language: English
• Subjects: Adult; Age Distribution; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; antiretroviral naïve; Antiviral agents; Body Mass Index; CD4 antigen; Clinical trials; Cytochrome-c oxidase; DNA; Electron transport chain; Enzymes; epidermal nerve fibre density; Female; Geriatrics; HIV; HIV Seropositivity - drug therapy; HIV Seropositivity - epidemiology; HIV Seropositivity - physiopathology; Human immunodeficiency virus; Humans; Infection; Leg; Male; Mitochondria; Mitochondrial DNA; Nerve Fibers - pathology; Nerves; Neuropathy; Neurotoxicity Syndromes - epidemiology; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - physiopathology; Oxidative phosphorylation; Peripheral blood mononuclear cells; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Peripheral Nervous System Diseases - physiopathology; Polyneuropathies - epidemiology; Polyneuropathies - etiology; Polyneuropathies - physiopathology; Predictive Value of Tests; Stavudine; Stavudine - adverse effects; Thailand - epidemiology; Toxicity
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/j.1468-1293.2012.01024.x

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 naïve 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