Neuropathogenesis: Therapy and Clinical Studies
Friday, 1:30 - 3:30 pm
Background: Peripheral neuropathy is the most common neurological complication of HIV infection and dideoxynucleoside antiretroviral (d-drug ARV) therapy. However risk factors for the presence and progression of HIV peripheral neuropathy have not been described in HAART-era cohorts.
Methods: We evaluated at baseline, 24 weeks, and 48 weeks 101 HIV-infected, ARV-experienced adults with CD4 lymphocyte count < 300 cells/mm3. Standardized assessments included neurological examination, nerve conduction studies, and quantitative sensory testing, with data summated into a total neuropathy score. Neuropathic pain was measured by Gracely and visual analogue scales. Skin biopsy was performed at the thigh and distal leg with assay of epidermal nerve fiber density (ENFD). The presence, severity and progression of peripheral neuropathy were related to clinical and laboratory demographics, and use of d-drug ARV. Multivariate analysis was performed, using a GEE linear model. For purposes of exploratory modeling, a significance level of 0.15 was used to identify potential predictors.
Results: Of the subjects, 90% were male, 60% were white, and the median age was 45; median CD4 was 169 cells/ mm3, and median log10 plasma HIV RNA was 2.95; 49% were receiving d-drug ARV at entry. The median total neuropathy score (range 0 to 36) was 8, with 38% of subjects classified as neuropathy-free, 10% asymptomatic for peripheral neuropathy, and 52% symptomatic. Significant progression in neuropathy from baseline to week 48 occurred only in the peripheral neuropathy-free group (mean total neuropathy score change = 1.16, SD = 2.76, p = 0.03). In this peripheral neuropathy-free group, 4 of 28 transitioned to asymptomatic neuropathy, and 6 of 28 to symptomatic peripheral neuropathy. Neuropathic pain was relatively stable over the course of the study, and significantly correlated with total neuropathy score at all time points. The only factors associated with progression in total neuropathy score were decreased baseline total neuropathy score, increased thigh/distal leg ENFD ratio and white race. CD4 and HIV RNA (baseline and change), and use of d-drugs were not predictive of total neuropathy score progression.
Conclusions: Peripheral neuropathy remains highly prevalent in HIV infection, and its course was relatively stable over 48 weeks. Previously established risk factors for peripheral neuropathy, including CD4 and HIV RNA, were not predictive for the presence or progression of neuropathy. While use of d-drugs did not predict progression of peripheral neuropathy, these results should be interpreted with caution due to possible acquisition bias.
Keywords: Neuropathy; Neurotoxicity; Cohort study