Abstract WMP21: Blood Biomarkers Of Endothelial And Macrocytic Activation Are Associated With Brain White Matter Microstructure In People Living With Hiv On Antiretroviral Treatment.

Abstract

Objective: To identify associations between specific serum inflammatory markers and structural white matter integrity as measured on brain diffusion tensor imaging (DTI) in middle-aged people living with HIV (PLWH). Methods: PLWH over 50 years of age residing in New York, NY participated in a cross-sectional study between January and July 2019. Demographic and magnetic resonance imaging data, along with blood samples, were collected. Least absolute shrinkage and selection operator (LASSO) regression was used to identify the most relevant variables associated with brain white matter fractional anisotropy (FA) and mean diffusivity (MD), among seventeen serum inflammatory markers, and control variables (listed in Table 1). Results: A total of 85 PLWH were included in the analysis. Mean age (SD) was 60 (6) years, 48% were men and 78% non-Hispanic black. All were taking antiretroviral therapy at enrollment. Among them, 75% had CD4 count ≥200 cell/mm 3 and viral load <400 copies/mL near the time of their MRI scans. We observed that, as the penalty factor (λ) increased in the LASSO regression, vascular endothelial growth factor (VEGF) (β=-0.052), monocyte chemoattractant protein 1 (MCP-1) (β=-0.001) and macrophage inflammatory proteins 1α (MIP-1α) (β=-0.007) and 1β (MIP-1β) (β=-0.074) remained in the LASSO model for FA. Similarly, VEGF (β=1.01x10 -4 ), MIP-1α (β=3.67x10 -6 ) and MIP-1β (β=7.12x10 -5 ) remained in the LASSO model for MD (Table 1). Conclusion: Prior research has linked VEGF to HIV-associated encephalopathy and MCP-1 to HIV-associated dementia, while both MIP-1α and MIP-1β have been associated with asymptomatic HIV infection. Our findings therefore may offer a mechanistic framework for those associations, indicating that chronic inflammation in the context of HIV infection may alter brain white matter microstructure. Such alterations may contribute to the development of HIV-associated central nervous system disorders.