Increased peripheral inflammation is associated with structural brain changes and reduced blood flow in virologically controlled people with HIV.

Abstract

While antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH on ART contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, the underlying mechanisms remain elusive. Our cohort consists of ART-adherent, virologically suppressed PWH (n=173; <50 copies/mL). Immune cell markers of overall immune health (CD4/CD8 T cell ratio), myeloid inflammation (CD16+ monocytes), and plasma markers of inflammatory status (sCD163 and sCD14) along with structural (volume) and functional (cerebral blood flow (CBF)) neuroimaging were measured in PWH. Decreased CD4/CD8 ratios correlated with reduced brain volume and higher inflammatory CD16+ monocytes were associated with reduced brain volume in total cortex and gray matter. An increase in plasma sCD14, a marker of acute peripheral inflammation due to circulating microbial products, was associated with reduced CBF within the frontal, parietal, temporal, and occipital cortices, and total gray matter. We observe that the CD4/CD8 ratio and the number of CD16+ monocytes, which are chronic immune cell markers, are associated with volumetric loss in the brain. Additionally, this study shows a potential new association between plasma sCD14 and CBF.