Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result i n up-regulation of the urokinase-type plasminogen activator receptor (uPAR/ CD87) on leukocytes in vitro and in vivo. The objective of this study was t o investigate whether this up-regulation is paralleled by higher serum leve ls of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whet her the serum level of suPAR is predictive of clinical outcome. Using an en zyme-linked immunosorbent assay, the level of suPAR was measured retrospect ively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Me ier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suP AR (greater than median) were associated with poor overall survival, and Ka ptan-Meier analysis on patients stratified by suPAR level demonstrated a co ntinuous increase in mortality rates with higher suPAR levers. After adjust ment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-micro globulin, and age-the prognostic strength of suPAR remained highly signific ant, indicating that the serum suPAR level is a novel, strong, and independ ent predictor of survival in HIV-1 infection. This report is the first to d emonstrate an important association between the plasminogen activator syste m and disease progression in HIV-1 infection, (C) 2000 by The American Soci ety of Hematology.