icon-    folder.gif   Conference Reports for NATAP  
  18th CROI
Conference on Retroviruses
and Opportunistic Infections
Boston, MA
February 27 - March 2, 2011
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Microbial Translocation (MT)-induced Immune Activation Associates to Atherosclerosis in cART treated HIV pos Patients
  Reported by Jules Levin
CROI 2011 March 2 Boston
E. Merlini*1, F. Bai1, E. Suardi1, G.M. Bellistri1, S. Negri1, M. Cristina 2, T. Bini 1, A. d'Arminio Monforte1 and G. Marchetti 1 1Dept of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, "San Paolo" Hospital - University of Milan - Italy ;2 Chair of Internal Medicine, "San Paolo" Hospital - University of Milan - Italy
Chronic inflammation and immune activation are now recognized as major risk factors for atherosclerosis (1). Indeed, there is mounting evidence to support the role of inflammation and endothelial activation and dysfunction in the development of plaque formation and progression of atherosclerosis in the general population (2,3).
In particular, elevated levels of proinflammatory cytokines, such as interleukin (IL)-6 are associated with subclinical atherosclerosis (4). Tumor necrosis factor (TNF)-alpha has been implicated in myocardial dysfunction after acute coronary syndromes (5).
In HIV disease, the immune system is chronically activated with increased levels of pro-inflammatory cytokines and activated T-lymphocytes.
In HIV/AIDS, immune hyperactivation has been recently proposed to be sustained by the passage in the bloodstream of bacterial bioproducts (microbial translocation), such as Lipopolysaccharide (LPS) that induces the expression of a wide range of proinflammatory mediators through TLR-4 pathways (6). TLR4 has been shown to be expressed in human lipid-rich atherosclerotic plaques (7,8).
Thus, systemic inflammation, and T cell activation have been recently proposed as major drivers of HIV-related atherosclerosis (9).
Given the possible role of immune activation/inflammation in the pathogenesis of atherosclerosis, we asked whether markers of inflammation and microbial translocation might associate with increased atherosclerosis as evaluated by carotid Intima Media Thickness (IMT) in HIV-infected patients.
HAART-treated virologically controlled HIV-positive patients with ATS-related vascular damage present an activated/senescent, apoptotic and pro-inflammatory immune profile, with higher proportion of CD127+CD8 T-cells, possibly suggesting persistent ongoing antigenic stimulation, and inflammation despite full HIV viremia control.
Interestingly, patients with atherosclerotic plaque also show higher circulating microbial sCD14. sCD14 levels were positively associated with carotid IMT and resulted predictor of pathological IMT and/or plaque in univariate analysis, but this was not confirmed in multivariate analysis (possibly due to the smaller size of analyzed samples).
By showing an association between sCD14 and carotid IMT, our findings allow to hypothesize that innate immunity to translocating bacterial products might contribute to increased risk of atherosclerosis in HAART-treated HIV pos pts.
We consecutively enrolled 163 HIV-infected patients on stable, virologically- suppressive HAART who underwent ultrasonography of the epi-aortic vessels.
Patients were divided into 3 groups on the basis of IMT:
· n= 112 (69%) with normal IMT (nIMT): IMT ≤ 1mm
· n= 22 (13%) with pathological IMT (pIMT): IMT between 1.1mm and 1.4 mm
· n= 29 (18%) with plaque: IMT ≥ 1.5 mm or IMT ≥ 1.1 mm and concomitant IMT increase ≥ 50% than adjacent districts







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