T-Cell Phenotypes,Apoptosis and Inflammation in HIV+ Patients on Virologically Effective cART with Early Atherosclerosis |
| |
Authors: | Esther Merlini Kety Luzi Elisa Suardi Alessandra Barassi Maddalena Cerrone Javier Sánchez Martínez Francesca Bai Gian Vico Melzi D’Eril Antonella D’Arminio Monforte Giulia Marchetti |
| |
Affiliation: | 1. Clinic of Infectious Diseases and Tropical Medicine, Department of Health Sciences, University of Milan, San Paolo Hospital, Milan, Italy.; 2. Laboratory of Clinical Analyses, Department of Health Sciences, University of Milan, San Paolo Hospital, Milan, Italy.; University of New South Wales, Australia, |
| |
Abstract: | ObjectiveWe 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).DesignWe studied 163 patients receiving virologically suppressive cART.MethodsWe measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression.ResultsOf 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ≥1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038) and apoptotic CD4+CD95+ (p = .01) and CD8+CD95+ cells (p = .003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57− memory CD4+ (p = .048) and CD28–CD57−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 levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors.ConclusionsDespite 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. |
| |
Keywords: | |
|
|