Brain large artery inflammation associated with HIV and large artery remodeling

Objective:To test the hypothesis that brain arteries from HIV+ cases have a greater degree of inflammation than brain arteries from HIV- cases, and that inflammation is associated with brain arterial remodeling.Design:Case-control study, cross-sectional.Methods:Brain arteries from 162 autopsy cases (84 with HIV) were systematically analyzed for thickness of the intima, media, and adventitia, and atherosclerosis and dolichoectasia. Inflammation was assessed with CD68(+) immunohistochemistry, and measured with a semiquantitative score reflecting the number and location (i.e., arterial layer) of activated macrophages infiltrating the arterial wall. Latent varicella zoster virus (VZV) was assessed with anti-VZV gene 63 product immunohistochemistry. Demographic and clinical variables were available in all cases, and longitudinal data about CD4(+) cell counts were available among cases with HIV. Multilevel generalized linear models were used to test the association between inflammation and HIV.Results:Arteries from HIV+ cases had a higher inflammation score (B=0.36, P=0.05) compared with arteries from HIV- cases, although the association was attenuated after controlling for demographic variables, vascular risk factors, and latent VZV (B=0.20, P=0.18). Although intimal inflammation was similar in cases with and without HIV, adventitial inflammation was associated with HIV. Intimal inflammation was associated with intracranial atherosclerosis independent of HIV status, but adventitial inflammation was associated with HIV-associated dolichoectasia in arteries with a thin media.Conclusions:Adventitial inflammation is associated with HIV and dolichoectasia independent of intracranial atherosclerosis. This suggests that differential inflammatory responses may play a role in intracranial atherosclerosis and dolichoectasia.