Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events During Antiretroviral Therapy-mediated Viral Suppression
| Autor: | Yonglong Zhang, Malcolm A. Finkelman, Ronald J. Bosch, Alan L. Landay, Daniela Moisi, Sara Gianella, Jesper Eugen-Olsen, Martin Hoenigl, Jochen Reiser, Carlee Moser, Michael M. Lederman, Amy Kantor, Nicholas T. Funderburg |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Adult Clinical Trials Group NWCS 411 study team HIV Infections Medical and Health Sciences Pathogenesis 0302 clinical medicine Interquartile range Receptors 2.1 Biological and endogenous factors 030212 general & internal medicine Aetiology Articles and Commentaries biology Viral Load Middle Aged Biological Sciences Infectious Diseases Urokinase Plasminogen Activator HIV/AIDS Female medicine.symptom Infection Lipopolysaccharide binding protein Microbiology (medical) Adult medicine.medical_specialty viral suppression 030106 microbiology Inflammation Microbiology Receptors Urokinase Plasminogen Activator suPAR 03 medical and health sciences Young Adult Acquired immunodeficiency syndrome (AIDS) Clinical Research Internal medicine non-AIDS mortality medicine Humans Aged lipopolysaccharide binding protein business.industry Odds ratio medicine.disease Clinical trial beta-D-glucan Good Health and Well Being SuPAR biology.protein business Biomarkers |
| Zdroj: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 69, iss 4 |
| Popis: | Author(s): Hoenigl, Martin; Moser, Carlee B; Funderburg, Nicholas; Bosch, Ronald; Kantor, Amy; Zhang, Yonglong; Eugen-Olsen, Jesper; Finkelman, Malcolm; Reiser, Jochen; Landay, Alan; Moisi, Daniela; Lederman, Michael M; Gianella, Sara; Adult Clinical Trials Group NWCS 411 study team | Abstract: BackgroundDespite 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.MethodsParticipants (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.ResultsAt 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.ConclusionsElevated 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. |
| Databáze: | OpenAIRE |
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