title: T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis.
abstract: 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).
  
  
  METHODS
  We studied 163 patients receiving virologically suppressive cART.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinic of Infectious Diseases and Tropical Medicine, Department of Health Sciences, University of Milan, San Paolo Hospital, Italy.
authors.forename: Esther
authors.initials: E
authors.lastname: Merlini
authors.forename: Kety
authors.initials: K
authors.lastname: Luzi
authors.forename: Elisa
authors.initials: E
authors.lastname: Suardi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barassi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Cerrone
authors.forename: Javier Sánchez
authors.initials: JS
authors.lastname: Martínez
authors.forename: Francesca
authors.initials: F
authors.lastname: Bai
authors.forename: Gian Vico Melzi
authors.initials: GV
authors.lastname: D'Eril
authors.forename: Antonella D'Arminio
authors.initials: AD
authors.lastname: Monforte
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis; D050197:Atherosclerosis / Q000150:complications* / Q000276:immunology; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D015331:Cohort Studies; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014463:Ultrasonography
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD