Tensor-valued diffusion MRI detects brain microstructure changes in HIV infected individuals with cognitive impairment.

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.

Role of non-classical monocytes in HIV-associated vascular cognitive impairment.

Despite antiretroviral treatment (cART), people living with HIV (PLWH) are more susceptible to neurocognitive impairment (NCI), probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, altered blood brain barrier (BBB) and transmigration of inflammatory monocytes are risk factors for developing cerebral small vessel disease (CSVD). In order to investigate if inflammatory monocytes exacerbate CSVD and cognitive impairment, 110 PLWH on cART and 110 age-, sex- and Reynold’s cardiovascular risk score-matched uninfected individuals were enrolled. Neuropsychological testing, brain magnetic resonance imaging and whole blood analyses to measure platelet-monocyte interaction and monocyte, endothelial activation were performed. Results demonstrated that PLWH exhibited increased levels of platelet-monocyte complexes (PMCs) and higher expression of activation molecules on PMCs. PLWH with CSVD had the poorest cognitive performance and the highest circulating levels of non-classical monocytes which exhibited significant inverse correlation with each other. Furthermore, markers of monocyte and endothelium activation were significantly positively correlated indicating BBB impairment. Our results confirm that interaction with platelets activates and drives monocytes towards an inflammatory phenotype in PLWH. In particular, elevated levels of non-classical monocytes may represent a common pathway to neuroinflammation, CSVD and subsequent cognitive impairment, warranting further longitudinal studies to evaluate responsiveness of this potential biomarker.