icon-    folder.gif   Conference Reports for NATAP  
  22nd Conference on Retroviruses and
Opportunistic Infections
Seattle Washington Feb 23 - 26, 2015
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T-Cell Activation and E-Selectin Associated with Coronary Plaque in HIV-Infected Youth: early predictors of potential heart disease found in HIV+ youth 22 YO
  Reported by Jules Levin
CROI 2015 Feb 23-26, Seattle, WA
A. Unsal1, K. Z. Abd-Elmoniem1, A. Rupert1, J. Kovacs1, J. B. Purdy1, R. Hazra1, C. Hadigan1, A. M. Gharib1 1National Institutes of Health, Bethesda, MD, USA
Program Abstract: Adolescents and young adults (AYA) infected with HIV early in life may be at increased risk of atherosclerotic cardiovascular disease (CVD). Chronic inflammation and circulating adhesion molecules may play a role in the early pathogenesis of atherosclerosis, however, the mechanism of vascular injury in this population is still unclear. The aim of this study was to measure biomarkers of cardiovascular injury and immune activation in relationship to coronary plaque burden in patients infected with HIV early in life.
5 AYA who acquired HIV early in life and 11 healthy controls were examined in this prospective cross-sectional study. All participants were free of active CVD at the time of evaluation. CT angiography was utilized for coronary plaque quantification. Number of atherosclerotic plaques, calcified and non-calcified, was determined in each of the 17 American Heart Association coronary segments.
Conclusions: Prior investigation in HIV+ adults identified an association between increased carotid lesions and T-cell activation markers. We identify a significant relationship between increased coronary plaque and levels of activated T-cells in AYA with life-long HIV. Further, soluble E-selectin, which has also been linked with carotid artery plaque and atherosclerosis, was positively correlated with coronary plaque in the present study. The presence of increased circulating adhesion molecules and markers of immune activation may be early predictors of atherosclerosis in AYA infected with HIV early in life.
Results: We studied HIV+ subjects (mean age 22; 15-29 years; 54% male) and control subjects (mean age 25; 22-29 years; 27% male). No calcified plaque was found in either group. No significant difference in number of plaque lesions between groups (HIV+ median 0, range 0-4, Control median 0, range 0-7, p=0.08). Activated CD8 T cells in the periphery, as measured by %CD8+CD38+DR+, was associated with increased coronary plaque in the HIV+ group (Table 1). Levels of activated peripheral CD8 T-cells (%CD8+CD38+DR+, p =0.025) were significantly associated with coronary plaque in HIV, but not levels of activated CD4 T-cells (%CD4+CD38+DR+). E-selectin was significantly associated with plaque in HIV+ subjects (p=0.006). In a multivariate analysis only %CD8+CD38+DR+ was significant (Table 1). Although P-selectin, sICAM-3, VCAM-1, TIMP-1, and MCP-1 levels were significantly elevated in HIV, these biomarkers did not relate to plaque, nor did lipopolysaccharide binding protein.
-> Individuals infected with HIV early in life have higher levels of immune activation, inflammation, and circulating adhesion molecules than controls
-> Viral suppression of HIV helps reduce but not completely reverse the chronic inflammatory state of HIV
-> Immune activation, in particular %CD8+CD38+DR+, is associated with coronary plaque in this cohort of patients with HIV
What is E-Selectin- http://en.wikipedia.org/wiki/E-selectin
The immunohistochemical expressions of E-selectin and PECAM-1 were significantly increased at intima in vulnerable plaques of acute coronary syndrome (ACS) group, especially in neovascular endothelial cells, and positively correlated with inflammatory cell density, suggesting that PECAM-1 and E-selectin might play an important role in inflammatory reaction and development of vulnerable plaque. E-selectin Ser128Arg polymorphism is associated with ACS, and it might be a risk factor for ACS.[24]
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a cell adhesion molecule expressed only on endothelial cells activated by cytokines





Figure 2: Box plot of levels of biomarkers of vascular dysfunction of control subjects vs. all HIV-infected patients and in the subset of HIV-infected patients with a viral load of >50 copies/mL. Box plots are displayed as median and IQR. * indicated for p-values < 0.05 compared to controls.