T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis

• Published in: PloS one 2012-09, Vol.7 (9), p.e46073-e46073
• Main Authors: Merlini, Esther, Luzi, Kety, Suardi, Elisa, Barassi, Alessandra, Cerrone, Maddalena, Martínez, Javier Sánchez, Bai, Francesca, D'Eril, Gian Vico Melzi, Monforte, Antonella D'Arminio, Marchetti, Giulia
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; Aged; AIDS; Anti-Retroviral Agents - therapeutic use; Antigens, CD - immunology; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - complications; Atherosclerosis - immunology; Biology; Care and treatment; Carotid Arteries - diagnostic imaging; CD28 antigen; CD38 antigen; CD4 antigen; CD57 antigen; CD8 antigen; CD95 antigen; Cell activation; Cohort Studies; Comparative analysis; Cytometry; Dosage and administration; Drug therapy; Endotoxemia; Enzyme-linked immunosorbent assay; Female; Flow cytometry; HIV; HIV - immunology; HIV infections; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immunity; Immunoglobulin G; Inflammation; Inflammation - complications; Inflammation - immunology; Interleukin 6; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes T; Male; Measurement methods; Medicine; Middle Aged; Mortality; Patients; Phenotype; Plaques; Regression analysis; Risk factors; Senescence; Studies; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tumor necrosis factor; Ultrasonography; Ultrasound
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046073

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). We studied 163 patients receiving virologically suppressive cART. We 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. Of 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. 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.