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Inflammatory Phenotypes Predict Changes in Arterial Stiffness following ART Initiation

Kelly, C; Tinago, W; Alber, D; Hunter, P; Luckhurst, N; Connolly, J; Arrigoni, F; ... Khoo, S; + view all (2020) Inflammatory Phenotypes Predict Changes in Arterial Stiffness following ART Initiation. Clinical Infectious Diseases 10.1093/cid/ciaa186. (In press). Green open access

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Abstract

BACKGROUND: Inflammation drives vascular dysfunction in HIV, but in low-income settings causes of inflammation are multiple, and include infectious and environmental factors. We hypothesised that patients with advanced immunosuppression could be stratified into inflammatory phenotypes that predicted changes in vascular dysfunction on ART. METHODS: We recruited Malawian adults with CD4<100 cells/ul two weeks after starting ART in the REALITY trial (NCT01825031). Carotid femoral pulse wave velocity (cfPWV) measured arterial stiffness 2, 12, 24 and 42 weeks post-ART initiation. Plasma inflammation markers were measured by electrochemiluminescence at weeks 2 and 42. Hierarchical clustering on principal components identified inflammatory clusters. RESULTS: 211 HIV-positive participants grouped into three clusters of inflammatory marker profiles representing 51 (24%) (cluster-1), 153 (73%) (cluster-2) and 7 (3%) (cluster-3) individuals. Cluster-1 showed markedly higher CD4 and CD8 T-cell expression of HLADR and PD1 vs cluster-2 and cluster-3 (all p<0.0001). Although small, individuals in cluster-3 had significantly higher levels of cytokines reflecting inflammation (IL6, IFNɣ, IP10, IL1RA, IL10), chemotaxis (IL8), systemic and vascular inflammation (CRP, ICAM1, VCAM1) and SAA (all p<0.001). In mixed-effects models, cfPWV changes over time were similar for cluster-2 vs cluster-1 (relative-fold-change 0.99 (95% CI 0.86-1.14, p=0.91, but greater in cluster-3 vs cluster-1 (relative-fold-change 1.45 (95% CI 1.01-2.09, p=0.045). CONCLUSIONS: Two inflammatory clusters were identified: one defined by high T-cell PD1 expression and another by a hyper-inflamed profile and increases in cfPWV on ART. Further clinical characterisation of these inflammatory phenotypes could help target vascular dysfunction interventions to those at highest risk.

Type: Article
Title: Inflammatory Phenotypes Predict Changes in Arterial Stiffness following ART Initiation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciaa186
Publisher version: https://doi.org/10.1093/cid/ciaa186
Language: English
Additional information: Copyright © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Arterial stiffness, Inflammatory phenotype, Sub-Saharan Africa
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10092603
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