Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events during Antiretroviral Therapy-mediated Viral Suppression

Martin Hoenigl, Carlee B. Moser, Nicholas Funderburg, Ronald Bosch, Amy Kantor, Yonglong Zhang, Jesper Eugen-Olsen, Malcolm Finkelman, Jochen Reiser, Alan Landay, Daniela Moisi, Michael M. Lederman, Sara Gianella

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Background: Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains associated with higher morbidity and mortality, driven, in part, by increased inflammation. Our objective was to identify associations between levels of plasma biomarkers of chronic inflammation, microbial translocation, and monocyte activation, with occurrence of non-AIDS events. Methods: Participants (141 cases, 310 matched controls) were selected from a longitudinal observational trial; all were virally suppressed on ART at year 1 and thereafter. Soluble urokinase plasminogen activator receptor (suPAR), lipopolysaccharide binding protein (LBP), beta-D-glucan (BDG), intestinal fatty-acid binding protein, oxidized low-density lipoproteins, and soluble CD163 were measured pre-ART, after 1-year of ART, and pre-event. At each time point, conditional logistic regression analysis assessed associations of the biomarkers with events and adjusted for relevant covariates to calculate odds ratios (ORs) according to 1 interquartile range (IQR) difference. Results: At all time points, higher levels of suPAR were associated with increased risk of non-AIDS events (OR per 1 IQR was 1.7 before ART-initiation, OR per 1 IQR was 2.0 after 1 year of suppressive ART, and OR 2.1 pre-event). Higher levels of BDG and LBP at year 1 and pre-event (but not at baseline) were associated with increased risk of non-AIDS events. No associations were observed for other biomarkers. Conclusions: Elevated levels of suPAR were strongly, consistently, and independently predictive of non-AIDS events at every measured time point. Interventions that target the suPAR pathway should be investigated to explore its role in the pathogenesis of non-AIDS-related outcomes in HIV infection.

Original languageEnglish (US)
Pages (from-to)676-686
Number of pages11
JournalClinical Infectious Diseases
Volume69
Issue number4
DOIs
StatePublished - Aug 15 2019
Externally publishedYes

Keywords

  • beta-D-glucan
  • lipopolysaccharide binding protein
  • non-AIDS mortality
  • suPAR
  • viral suppression

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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