Urokinase Plasminogen Receptor Levels Linked to Non-AIDS Related Events During ART Viral Suppression

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Interventions that target the soluble urokinase plasminogen activator receptor pathway should be investigated to explore its role in the pathogenesis of non-AIDS-related outcomes in HIV-infection.
Interventions that target the soluble urokinase plasminogen activator receptor pathway should be investigated to explore its role in the pathogenesis of non-AIDS-related outcomes in HIV-infection.

In patients with HIV, elevated levels of soluble urokinase plasminogen activator receptor are associated with non-AIDS events, according to study results published in Clinical Infectious Diseases.

The study included participants with non-AIDS events (n=141) and matched controls (n=310). Participants were enrolled from prior studies conducted by the AIDS Clinical Trials Group (ACTG). All participants were antiretroviral therapy (ART)-naïve upon enrollment, had a plasma HIV-1 RNA level of <400 copies/mL at 48 weeks after ART initiation, and maintained a plasma HIV RNA level of <400 copies/mL at all subsequent time points.

Case participants were individuals who had a myocardial infarction or stroke, a non–AIDS-defining malignancy or serious bacterial infection, or died from a non-accidental non-AIDS-related event.

The researchers measured levels of soluble urokinase plasminogen activator receptor, lipopolysaccharide binding protein, beta-D-glucan, intestinal fatty acid binding protein, oxidized low-density lipoprotein (LDL), and soluble CD163 before initiation of ART, after 1 year of ART, and pre-event. They used conditional logistic regression analysis to determine associations of these biomarkers with events.

The results indicated that higher levels of soluble urokinase plasminogen activator receptor were associated with increased risk for non-AIDS events at all time points, with an odds ratio (OR) per 1 interquartile range of 1.7 before ART-initiation, 2.0 after 1-year of suppressive ART, and 2.1 pre-event.

The researchers also found that higher levels of beta-D-glucan and lipopolysaccharide binding protein were associated with increased risk for non-AIDS events, but only at year 1 and pre-event.

They did not find any associations for other biomarkers.

“Once validated, [soluble urokinase plasminogen activator receptor levels] may be used for future interventional studies aimed at reducing morbidity/mortality in ART-treated HIV infection,” the researchers wrote. “Interventions that target the [soluble urokinase plasminogen activator receptor] pathway should be investigated to explore its role in the pathogenesis of non–AIDS-related outcomes in HIV infection.”

Reference

Hoenigl M, Moser C, Funderburg N, et al. Soluble urokinase plasminogen activator receptor (suPAR) is predictive of non-AIDS events during antiretroviral therapy-mediated viral suppression [published online November 12, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy966

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