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


Correspondence: Dr Cecilia M. Shikuma, Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii at Manoa, 3675 Kilauea Ave. Young Bldg 5th Floor, Honolulu, HI 96816, USA. Tel: (808) 737 2751; fax: (808) 735 7047; e-mail:



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.


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.


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 < 0.01), older age (P < 0.01), increased body mass index (BMI) (P = 0.04), increased height (P = 0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P = 0.02) were associated with lower distal leg ENFD.


Older age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV-infected subjects free of neuropathy prior to initiation of first-time ARV therapy.