Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). current CD4+, VLs and total length of time on cART. Despite comparable ratios of CD38-conveying CD8+ cells (p?=?.95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p?=?.038) and apoptotic CD4+CD95+ (p?=?.01) and SRT3109 CD8+CD95+ cells (p?=?.003). In comparison to nIMT patients, iIMT patients tended to have lower figures of early differentiated CD28+CD57? memory CD4+ (p?=?.048) and CD28CCD57?CD8+ cells (p?=?.006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p?=?.046). No differences in anti-CMV IgG was shown. Although circulating SRT3109 levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical aerobic predictors. Findings Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further. Introduction HIV-infected patients are at an increased risk for cardiovascular events in comparison to age-matched HIV-negative controls , . The reason for this increased risk is usually multifactorial and entails traditional risk factors, exposure to specific SELPLG antiretroviral drugs and HIV contamination itself  , . The conversation between HIV contamination and cardiovascular disease has been a major concern of the HIV field since the early cART era, when large cohort studies exhibited a relationship between antiretroviral exposure and myocardial infarction C. Recent studies have launched the hypothesis that chronic inflammation and immune activation can contribute to the initiation and progression of atherosclerosis (ATS) in the setting of HIV contamination C. Recently, some authors have also suggested an association between T-cell activation/senescence and markers of subclinical carotid artery disease, even among patients on stable cART . The role of inflammation and endothelial activation/disorder in the development of ATS has SRT3109 been analyzed extensively in the general populace, and several markers, such as sVCAM-1, sICAM-1 and von Willebrand factor antigen, have been shown to reliably indicate the increased activation of endothelial cells in ATS , . Tumor necrosis factor (TNF)- has been implicated in myocardial disorder producing from acute coronary syndrome , and high levels of C-reactive protein (CRP) and interleukin (IL)-6 have been associated with subclinical ATS C. In recent years, microbial translocation (MT) has been proposed as a main mechanism behind immune hyperactivation during HIV contamination C, and recent studies have suggested the potential involvement of MT in the pathogenesis of ATS , . The Bruneck study in 1999 provided the first epidemiological evidence in support of a clinical association between levels of lipopolysaccharide (LPS), MT markers, and cardiovascular risk . Very recently, data from the SMART study suggested that high levels of circulating sCD14, a soluble form of the LPS receptor expressed by monocytes, were associated with an increased risk of all-cause mortality, suggesting a link between stomach damage, inflammation, immune activation and CD4+ T-cell loss . Long-term successfully treated HIV infected patients have been shown to present amazingly high levels of CMV-specific effector cells, comparable to that observed in the elderly , allowing to speculate a role of the CMV-specific inflammatory response in immunosenescence and non-AIDS morbidity and mortality. Indeed, Hsue pIMT (22 C IU/ml vs 22 C p?=?.0.86), nor comparing nIMT, iIMT and plaque (22 C IU/ml vs 22 C IU/ml vs 19 C IU/ml; p?=?.57). (Physique 3G). No significant association was shown between anti-CMV IgG titer, CD8+CD38+CD45R0+ (Rho?=??0.052, p?=?0.592) and CD4+/CD8+CD95+ T-cells (Rho?=?0.053, p?=?0.589; Rho?=?0.061, p?=?0.534, respectively). Oddly enough enough, when the correlation analysis was performed only in patients with pathological IMT (pIMT), a slight positive correlation was shown between anti-CMV IgG titer and pro-apoptotic CD4+CD95+ T-cells (Rho?=?0.41, p?=?0.0136). Recognition of Factors Associated with Carotid Intima-media Thickness by Univariate and Multivariate Analyses Traditional risk factors and immunological or soluble markers that displayed a p value <.01 for the Mann-Whitney U test were included in a logistic regression model to investigate the indie factors associated with increased IMT and/or plaques, as shown in Table 2a. Given the integrative nature of SRT3109 FRS and HOMA-IR that altogether include several traditional cardiovascular risk factors, for multivariate models we specifically selected not to include other risk factors that were not associated in the univariate models. Table 2 Regression models to explore impartial factors.