The aim of this study is to ascertain the burden of pre-clinical atherosclerotic changes in the brains of young adult males with HIV and explore the impact of anti-retroviral therapy (ART). The study design is case-control, cross-sectional. Histological sections from HIV-positive post-mortem brain samples, with no associated opportunistic infection, from the MRC Edinburgh brain bank were evaluated. These were age and sex matched with HIV-negative controls. Immunohistochemical stains were performed to evaluate characteristics of atherosclerosis. The pathological changes were graded blinded to the HIV status and a second histopathologist reassessed 15%. Univariable models were used for statistical analyses; p ≤ 0.05 was considered significant. Nineteen HIV-positive post-mortem cases fulfilled our inclusion criteria. Nineteen HIV-negative controls were selected. We assessed mostly small-medium-sized vessels. For inflammation (CD45), 7 (36%) of the HIV+ had moderate/severe changes compared with none for the HIV− group (p < 0.001). Moderate/severe increase in smooth muscle remodeling (SMA) was found in 8 (42%) HIV+ and 0 HIV− brains (p < 0.001). Moderate/severe lipoprotein deposition (LOX-1) was found in 3 (15%) and 0 HIV−brains (p < 0.001). ART was associated with less inflammation [5 (63%) no ART versus 2 (18%) on ART (p = 0.028)] but was not associated with reduced lipid deposition or smooth muscle damage. In HIV infection, there are pre-clinical small- to medium-sized vessel atherosclerotic changes and ART may have limited impact on these changes. This could have implications on the increasing burden of cerebrovascular disease in HIV populations and warrants further investigation.

IntroductionThe spectrum of encephalitis, a condition of brain inflammation and leucocyte infiltration, is expanding. Modern peripheral testing has resulted in fewer brain-biopsies. Consequently, our understanding of leucocyte-subsets driving inflammation is poorly understood.MethodsThe Walton Centre Brain-Bank was screened over 10 years, identifying all cases of biopsy and post-mortem tissue with encephalitis. Tissue underwent haemotoxylin/eosin stain, and immunohistochemical analysis for CD3, CD4, CD8, CD68, and CD79a. The immediate perivascular and surrounding parenchymal infiltrate quantitatively assessed.ResultsOf nine cases, two were herpes simplex virus (HSV), four immune-mediated, and three of unknown cause. In comparison to those of unknown cause, HSV had a greater proportion of CD4 and CD68 positive cells in the perivascular and immediate parenchyma respectively (p=0.007 and p=0.004). Neutrophils were only identified in HSV. Immune-mediated cases generally had a limited inflammatory infiltrate, similarly to unknown cases. Although one paraneoplastic case had a marked inflammatory infiltrate, including CD8 positive cells.ConclusionsOur study describes potentially important differences in the relative leucocyte populations in the parenchyma of patients with encephalitis, which may have diagnostic and therapeutic implications. Further studies are planned to distinguish invading macrophage/monocytes from resident microglia in a transgenic murine model.