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Discordance between peripheral and colonic markers of inflammation during suppressive ART.

ABSTRACT: OBJECTIVE:Persistent systemic inflammation is associated with the inability of some HIV-infected patients to normalize circulating CD4 T-cell levels after years of suppressive antiretroviral therapy. In this study, we sought to understand whether such systemic inflammation is also associated with detectable signs of inflammation in biopsies from the rectosigmoid colon. DESIGN:Immunologic and virological parameters were studied in the peripheral blood and in rectosigmoid colon biopsies from individuals with viral suppression for at least 2 years and with peripheral CD4 T-cell levels of <350 cells per cubic millimeter (immunologic nonresponders, n = 18) or >500 cells per cubic millimeter (immunologic responders, n = 16). METHODS:Peripheral blood and rectosigmoid colon biopsies were analyzed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. RESULTS:Nonresponders had elevated T-cell activation and inflammatory cytokines in the circulation, but inflammatory gene expression in colon biopsies was not different as compared with responders, and there was little relationship between blood and colon markers of inflammation. Blood inflammatory markers were positively associated with soluble CD14 levels indicative of monocyte activation. CONCLUSIONS:These findings demonstrate that, in the context of treated HIV disease, it is easier to detect parameters of inflammation (including blood monocyte activation) in the peripheral blood than in isolated rectosigmoid colon biopsies. Accordingly, interventions to block such inflammation in this population might be most conveniently and accurately assessed in blood.

SUBMITTER: Dunham RM

PROVIDER: S-EPMC3997573 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Discordance between peripheral and colonic markers of inflammation during suppressive ART.

Dunham Richard M RM Vujkovic-Cvijin Ivan I Yukl Steven A SA Broadhurst Mara J MJ Loke Pʼng P Albright Rebecca G RG Wong Joseph K JK Lederman Michael M MM Somsouk Ma M Hunt Peter W PW Martin Jeffrey N JN Deeks Steven G SG McCune Joseph M JM

Journal of acquired immune deficiency syndromes (1999) 20140201 2

<h4>Objective</h4>Persistent systemic inflammation is associated with the inability of some HIV-infected patients to normalize circulating CD4 T-cell levels after years of suppressive antiretroviral therapy. In this study, we sought to understand whether such systemic inflammation is also associated with detectable signs of inflammation in biopsies from the rectosigmoid colon.<h4>Design</h4>Immunologic and virological parameters were studied in the peripheral blood and in rectosigmoid colon biop ...[more]

PMID: 24121758

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Project description:BackgroundDefining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.MethodsWe conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.ResultsHigher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.ConclusionsInterventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.

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Discordance between peripheral and colonic markers of inflammation during suppressive ART.

Publications

Discordance between peripheral and colonic markers of inflammation during suppressive ART.

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