Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV

Abstract

HIV-infected individuals are at increased risk of cardiovascular disease (CVD), but the arterial vascular functions affected by persistent innate and cellular immune activation are not well described. We assessed the relationship between immunologic and vascular parameters in 70 HIV-infected adults on efavirenz, tenofovir, and emtricitabine with more than 2 years of virologic suppression and no history of CVD. We measured brachial artery flowmediated dilation (FMD) using ultrasound and circulating intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by multiple immunoassay. We also measured circulating naive (CD45RO, and memory (CD45RO + ) CD4+ and CD8 + T cell subsets by flow cytometry, and macrophage activation markers by ELISA and multiple immunoassay. Regression models were adjusted for age, sex, smoking, duration of antiretroviral therapy (ART), and body mass index. Median age was 45 years (IQR 39, 50), median CD4+ count 701 cells/ll (IQR 540, 954), and 43% were female. Lower brachial FMD was associated with a higher percentage of activated CD8 + T cells ( p < .01), but not associated with macrophage activation. In contrast, higher ICAM-1 and VCAM-1 were associated with sCD163 ( p < = .01 for both), macrophage inflammatory protein-1a ( p < = .02 for both), and sCD14 ( p = .01 for ICAM-1 only). These findings are consistent with the hypothesis that circulating CD8 + T cell activation may impair arterial smooth muscle relaxation, while macrophage activation has a role in the expression of endothelial cell proteins involved in immune cell translocation. Both innate and cellular immune activation appear to promote arterial vascular disease in HIV-infected persons on ART using differing mechanisms.

HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress

“…Conversely, other inflammatory biomarkers, including IL-8 and RANTES were directly correlated with improved FMD in this group. These results contrast with those of Grome et al [ 51 ] who found that activated CD8+ cells, but not sTNFRII, were associated with FMD in 70 HIV-infected patients who were similarly treated with FTC/TDF/EFV. We also found that RANTES was significantly correlated with FMD, but not FMD/RHVTI in the HIV- group.…”

Severe periodontitis is more common in HIV- infected patients

“…It is postulated that the increased prevalence of cardiovascular diseases in HIV patients is due to activation of the immune system. Specifically, macrophages and monocytes activation, which play a significant role in atherogenesis, in combination with deregulation of CD8+ T-cells, are associated with higher values of carotid intimal media thickness and arterial stiffness 41 Likewise, HIV and periodontitis could interact and promote development of ageassociated diseases 23,42 . We could not confirm that diabetes and cardiovascular diseases were significant risk factors for periodontitis in our HIV-infected patients, however.…”

HIV-1–Associated Atherosclerosis

“…Even HIV elite controllers have abnormally high T cell activation levels, which may contribute to progressive CD4 + T cell loss, even without measurable viremia (52). Chronic immune activation might contribute to the initiation of endothelial activation and subsequent atherogenesis (53), and these markers of T-cell activation are correlated with atherosclerosis in several studies (50–56).…”