Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.

Neuropsychiatric disorders in HIV infection: impact of diagnosis on economic costs of care.

BACKGROUND: HAART is associated with a growing prevalence of HIV-associated neuropsychiatric disorders (NPD) despite improved overall survival. OBJECTIVE: To investigate the added direct costs of medical care for patients with and without NPD. METHODS: Nine dimensions of patient-specific costs [as costs per patient per month (CPM)] were followed prospectively between 1997 and 2003 in a community-based HIV/AIDS clinic for HIV-1-seropositive patients with a diagnosis of NPD (n = 188) and without (n = 153). Patients with NPD were stratified into subgroups of cognitive impairment (CI), peripheral neuropathies (PN), or other neuropsychiatric disorders (OND). RESULTS: Compared with the non-NPD group ($916), patients in the NPD group showed an increased mean CPM during the 12-month intervals immediately preceding and subsequently following NPD diagnosis [$1371 (P < 0.001) and 1463 US dollars (P < 0.001), respectively], but not at 18 months prior to diagnosis (1061 US dollars; P > 0.05). Intragroup comparisons between 12 month post-diagnosis and 18 month pre-diagnosis showed a mean CPM increased of 67% (1613 US dollars; P < 0.001) with CI, 31% (1490 US dollars; P < 0.01) with PN, and 33% (1362 US dollars; P < 0.01) with OND. Increased numbers of clinic and physician visits, non-antiretroviral drugs and home care accounted for the higher mean CPM (P < 0.05) both pre-and post-diagnosis within the NPD group. CONCLUSIONS: Neuropsychiatric disorders in patients with HIV/AIDS increase medical costs both before and after diagnosis, primarily owing to the management of the neuropsychiatric illness. Cost analyses offer useful measures of evolving patient needs, and provide a basis for allocation of healthcare resources.