Abstract
BackgroundSerum concentrations of soluble urokinase-type plasminogen activator receptor (suPAR) have a strong independent association with HIV-1-related mortality. The practical utility of plasma suPAR in assessing short-term all-cause mortality risk was evaluated in patients with advanced immunodeficiency enrolling in an antiretroviral treatment (ART) programme in South Africa.MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to measure plasma concentrations of suPAR in patients at the time of enrolment to the ART programme. The association between plasma suPAR concentrations, baseline patient characteristics and cohort outcomes after 4 months of ART were determined.ResultsPatients (n = 293, 70% female) had a median age of 33 years and were followed up for a median of 5 months from enrolment. The median CD4 cell count was 47 cells/μl (IQR = 22–72) and 38% of patients had WHO stage 4 disease. 218 (74%) patients remained alive after 4 months of ART; 39 (13%) died and 36 (12%) were lost to the programme for other reasons. Patients who died had significantly higher plasma suPAR concentrations compared to those who either survived (P < 0.01) or left the programme for other reasons (P < 0.043). In multivariate analysis, higher log10 suPAR concentrations were significantly associated with lower CD4 cell counts, WHO clinical stage 4 disease and male sex. In multivariate analysis to identify factors associated with death, log10 suPAR concentration was the most strongly associated variable (P < 0.001). However, examination of sensitivity and specificity characteristics using receiver operating characteristic (ROC) analysis revealed that results from this assay did not have a discriminatory cut-point to provide clinically useful information.ConclusionPlasma suPAR concentration was the strongest independent predictor of short-term mortality risk among patients with advanced immunodeficiency enrolling in this ART programme. However, lack of a discriminatory threshold did not permit this marker to be used to triage patients according to short-term mortality risk.
Highlights
Serum concentrations of soluble urokinase-type plasminogen activator receptor have a strong independent association with HIV-1-related mortality
A stored plasma sample was available for measurement of soluble urokinase-type plasminogen activator receptor (suPAR) concentration in 293 (83%) patients and these were included in the study
Baseline characteristics and outcome of patients enrolling in the antiretroviral treatment (ART) programme who were included in the analysis
Summary
Serum concentrations of soluble urokinase-type plasminogen activator receptor (suPAR) have a strong independent association with HIV-1-related mortality. The practical utility of plasma suPAR in assessing short-term all-cause mortality risk was evaluated in patients with advanced immunodeficiency enrolling in an antiretroviral treatment (ART) programme in South Africa. A report from a South African cohort found that mortality occurring in the one month period while patients were preparing for ART accounted for 67% of early in-programme deaths [7]. This suggests that even short delays in starting ART may be associated with considerable mortality risk. Additional delays may arise due to the practical constraints imposed by the sheer numbers of patients seeking to start treatment in some settings and this may require some form of patient prioritisation
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