Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment.

Abstract

BACKGROUND:

Defining 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.

METHODS:

We 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.

RESULTS:

Higher 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.

CONCLUSIONS:

Interventional 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.

• Authors: Allan R Tenorio, Yu Zheng, Ronald J Bosch, Supriya Krishnan, Benigno Rodriguez, Peter W Hunt, Jill Plants, Arjun Seth, Cara C Wilson, Steven G Deeks, Michael M Lederman, Alan L Landay
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 210 Issue 8 Pg. 1248-59 (Oct 15 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24795473 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-HIV Agents
• Biomarkers
• RNA, Viral

Topics

• Adult
• Aged
• Anti-HIV Agents (therapeutic use)
• Biomarkers (metabolism)
• Blood Coagulation (physiology)
• Case-Control Studies
• Female
• HIV Infections (complications, drug therapy)
• Humans
• Inflammation (metabolism)
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• RNA, Viral (blood)
• T-Lymphocytes (physiology)
• Viral Load
• Young Adult