Abstract
BackgroundHigh blood levels of soluble urokinase Plasminogen Activator Receptor (suPAR) are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals. Research on the clinical value of suPAR in HIV-1 infection led to the development of the suPARnostic® assay for commercial use in 2006. The aim of this study was to: 1) Evaluate the prognostic value of the new suPARnostic® assay and 2) Determine whether polymorphisms in the active promoter of uPAR influences survival and/or suPAR values in HIV-1 patients who are antiretroviral therapy (ART) naive.MethodsDNA samples were collected retrospectively from 145 Danes infected with HIV-1 with known seroconversion times. In addition, plasma was collected retrospectively from 81 of these participants for use in the suPAR analysis. Survival was analysed using Kaplan Meier analysis.ResultsSurvival was strongly correlated to suPAR levels (p < 0.001). Levels at or above 6 ng/ml were associated with death in 13 of 27 patients within a two-years period; whereas only one of 54 patients with suPAR levels below 6 ng/ml died during this period. We identified two common uPAR promoter polymorphisms: a G to A transition at -118 and an A to G transition at -465 comparative to the transcription start site. These promoter transitions influenced neither suPAR levels nor patient survival.ConclusionPlasma suPAR levels, as measured by the suPARnostic® assay, were strongly predictive of survival in ART-naïve HIV-1 infected patients. Furthermore, plasma suPAR levels were not influenced by uPAR promoter polymorphisms.
Highlights
High blood levels of soluble urokinase Plasminogen Activator Receptor are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals
An elevated level of suPAR is predictive of negative clinical outcome in a number of different diseases such as HIV1[2], tuberculosis [3], pneumococcal bacteraemia [4], rheumatoid arthritis [5], multiple sclerosis [6] and certain forms of cancer [7,8]. suPAR is an independent marker of survival in HIV-1 infection with a prognostic strength similar to that of CD4+ T-cell count and HIV-1 viral load [2,9]
For the Kaplan Meier analysis, patients were divided into three sized groups of 27 patients based on their respective suPAR levels
Summary
High blood levels of soluble urokinase Plasminogen Activator Receptor (suPAR) are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals. The aim of this study was to: 1) Evaluate the prognostic value of the new suPARnostic® assay and 2) Determine whether polymorphisms in the active promoter of uPAR influences survival and/or suPAR values in HIV-1 patients who are antiretroviral therapy (ART) naive. Patients with HIV infection receive regular clinical followup to assess the need for more invasive treatment regimens such as initiation of ART. This assessment relies on the evaluation of HIV RNA viral load and CD4 cell count; the former of which requires expensive, high technology laboratory facilities. An elevated level of suPAR is predictive of negative clinical outcome in a number of different diseases such as HIV1[2], tuberculosis [3], pneumococcal bacteraemia [4], rheumatoid arthritis [5], multiple sclerosis [6] and certain forms of cancer [7,8]. suPAR is an independent marker of survival in HIV-1 infection with a prognostic strength similar to that of CD4+ T-cell count and HIV-1 viral load [2,9]
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