Plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) and early mortality risk among patients enrolling for antiretroviral treatment in South Africa.
BACKGROUND
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.


METHODS
An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma concentrations of suPAR in patients at the time of enrollment to the ART programme. The association between plasma suPAR concentrations, baseline patient characteristics and cohort outcomes after 4 months of ART were determined.


RESULTS
Patients (n = 293, 70% female) had a median age of 33 years and were followed up for a median of 5 months from enrollment. The median CD4 cell count was 47 cells/mul (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.


CONCLUSIONS
Plasma 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.
Lawn
Stephen D
SD
Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. stevelawn@yahoo.co.uk
Myer
Landon
L
Bangani
Nonzwakazi
N
Vogt
Monica
M
Wood
Robin
R
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology / Q000401:mortality; D015497:HIV-1; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator