Search

People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z-score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV., (Copyright © 2013 Wiley Periodicals, Inc.)

The prevalence of HIV-associated neurocognitive disorder has not changed from the pre- to the potent antiretroviral therapy era, remaining at approximately 50%. In research settings, mild neurocognitive disorder (MND) and so-called asymptomatic neurocognitive impairment (ANI) are now more common than HIV-associated dementia. The diagnosis of ANI is misleading because functional deficits, when tested in a laboratory, and degree of neuropsychologic testing abnormalities are often comparable in patients with ANI and those with symptomatic MND. Age-related comorbidities increase the risk of cognitive impairment in HIV infection. In a cohort of patients aged 60 years or older with excellent antiretroviral therapy adherence, correlates to cognitive impairment were apolipoprotein (Apo) E4 genotype and a novel measure of the effectiveness of antiretroviral drugs in monocytes, the monocyte efficacy (ME) score, with trend associations for diabetes and nadir CD4+ cell count. Management of impairment includes ensuring that patients are on and adhere to antiretroviral therapy and addressing comorbidities. Switching from effective and well-tolerated antiretroviral therapy for patients with mild cognitive impairment is not routinely recommended, but this must still be addressed on a case-by-case basis. This article summarizes a presentation by Victor G. Valcour, MD, at the IAS-USA continuing education program held in Atlanta, Georgia, in April 2013.

Objective: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk., Design: Cross-sectional analysis within the Hawaii Aging With HIV Cohort., Methods: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses., Results: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores., Conclusions: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

ObjectivesDistal 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.MethodsDistal 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.ResultsIn 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