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

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 < 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. CONCLUSIONS: 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.

Screening for human immunodeficiency virus (HIV) dementia in an HIV clade C-infected population in India.

Although human immunodeficiency virus (HIV) clade C virus infects the largest populations worldwide, to date there are no prospective studies reported thus far to determine the incidence or prevalence of HIV dementia in this population. HIV clade C virus is a CCR5-tropic virus and thus predominantly infects macrophages, which are the key cells implicated in the pathogenesis of HIV dementia. However, HIV dementia has only rarely been reported in these populations. The authors thus used a recently developed International HIV Dementia Scale (IHDS) to screen a well-characterized cohort of HIV-infected discordant couples in Pune, India. 48 HIV+ subjects with CD4 cell count <200 cells/mm(3) and 48 HIV- subjects were studied. The HIV+ subjects had significantly lower IHDS scores compared to the HIV- subjects. 35% of the HIV+ subjects and 15% of the HIV- subjects scored < 10 on the IHDS. These observations suggest that the prevalence of HIV dementia may be higher in this population than previously reported. More importantly, it demonstrates that the IHDS can be used as a screening tool in the Indian population.