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

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

Research output: Contribution to journalArticlepeer-review

441 Scopus citations

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-totryptophan (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.

Original languageEnglish (US)
Pages (from-to)1248-1259
Number of pages12
JournalJournal of Infectious Diseases
Volume210
Issue number8
DOIs
StatePublished - Oct 15 2014
Externally publishedYes

Keywords

  • ART
  • HIV
  • Immune activation
  • Inflammation
  • Non-AIDS morbidity

ASJC Scopus subject areas

  • General Medicine

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