Background: HIV-infected individuals may display chronic brain inflammation. It is unclear whether this inflammation may play a role in brain arterial pathologies that predispose patients with HIV to stroke. We tested the hypothesis that T cell infiltrates would be associated with brain arterial pathology.
Methods: Large brain arteries from 162 patients (84 with HIV) were used in immunohistochemical analysis to detect CD3, a pan T cell marker. A semi-quantitative score of 0 to 3 (absent, mild, moderate, severe) was created by visually rating CD3+ cells within each arterial layer (intima, media, and adventitia). Arterial stenosis, lumen-to-wall ratio and presence of atherosclerosis were measured in each arterial segment of the circle of Willis using previously reported methods of good to excellent reliability. All models were adjusted for co-dependence between arteries of the same subject as well as for age, sex, ethnicity, vascular risks factors, cocaine use and artery type and location.
Results: Brain arteries from HIV+ individuals had lower adventitial CD3 scores than HIV- (B = -1.65, p = 0.004). Further stratification demonstrated that the decreased arterial CD3 score was significant only among HIV+ subjects with premortem CD4 counts < 200 cells/μl (B = -2.28, p <0.001). Among HIV+ individuals with premortem CD4 counts ≥ 200 cells/μl, CD3 arterial scores were associated with brain atherosclerosis (B = 0.74, p=0.04). Independent of HIV status, CD3 score was associated with decreased lumen-to-wall ratio (B = -0.37, p = 0.02) and percentage luminal stenosis (B = 1.99, p = 0.004). Among HIV+ cases, higher CD3 score was noted with higher CD4 count at death (per 50, B=0.43, P=0.001), hypertension (B=7.14, P<0.001), male sex (B=6.29, P=<0.001) and prior opportunistic infections (B=3.24, P=0.008) while a lower CD3 score was noted among diabetics (B=-5.36, P<0.001) and reported use of antiretroviral at death (B=-1.39, P=0.01).
Conclusions: Among HIV+ individuals with premortem CD4 counts ≥ 200, there exists an association between brain arterial lymphocytic activity with atherosclerosis. These findings may suggest a role for lymphocytic inflammation in HIV-related atherosclerosis in the setting of immune reconstitution.