T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis
Author(s)
Type
Journal Article
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). DESIGN: 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.
Date Issued
2012-09-27
Date Acceptance
2012-08-27
Citation
PLoS One, 2012, 7 (9)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS One
Volume
7
Issue
9
Copyright Statement
© 2012 Merlini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/23029393
PII: PONE-D-12-12007
Subjects
Adult
Aged
Anti-Retroviral Agents
Antigens, CD
Apoptosis
Atherosclerosis
Carotid Arteries
Cohort Studies
Female
HIV
HIV Infections
Humans
Inflammation
Lymphocyte Activation
Male
Middle Aged
Phenotype
T-Lymphocytes
Ultrasonography
Publication Status
Published
Coverage Spatial
United States
Article Number
ARTN e46073