Brain Large Artery Lymphocytic Inflammation and Human Immunodeficiency Virus-Related Brain Arterial Remodeling

The pathogenesis of increased stroke risk in human immunodeficiency virus (HIV) remains unclear. Our study investigated the relationship between adventitial and intimal CD3⁺ T cells and brain arterial remodeling that potentially contributes to HIV-related vasculopathy and stroke. Large brain arteries from 84 HIV⁺ cases and 78 HIV^- cases were analyzed to determine interadventitial and luminal diameters, intimal and wall thickness, percent stenosis, and the presence of atherosclerosis. Immunohistochemical analysis was performed to detect and visually score CD3, a pan-T-cell marker, in the intima and adventitia. Our study showed that numbers of adventitial CD3⁺ T cells are lower among persons with HIV than among those without HIV, especially if CD4 counts are <200, though intimal CD3⁺ T cell numbers did not differ by HIV status. Among those with HIV but CD4 counts of <200 at the time of death, intimal CD3⁺ T cells were associated with hypertrophic outward remodeling, while among those with HIV and CD4 of >200 or HIV^- controls, intimal CD3⁺ T cells were associated with hypertrophic inward remodeling. We conclude that intimal lymphocytic inflammation is involved in brain arterial remodeling that may contribute to HIV-related cerebrovascular pathology.IMPORTANCE Although mortality from human immunodeficiency virus (HIV) has decreased with the use of combination antiretroviral therapies, there is now an increased risk of cardiovascular and cerebrovascular disease associated with HIV. Thus, there is a need to understand the pathogenesis of stroke in HIV infection. Our study examines how lymphocytic inflammation in brain arteries may contribute to increased cerebral vasculopathy. With this understanding, our study can potentially help direct future therapies to target and prevent brain arterial remodeling processes associated with HIV.