Objectives: To examine mechanisms underlying the increased inflammatory state of HIV-infected patients, by investigating the association of HIV-related factors, demography, lifestyle, and body composition with the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR).
Methods: suPAR was measured in EDTA-plasma and associated with HIV-related factors (HIV-duration, combination antiretroviral treatment (cART), nadir CD4+ cell count, CD4+ cell count, and HIV RNA); demography; lifestyle; and body composition determined by Dual energy X-ray Absorptiometry (DXA) scan, in multiple linear regression analyses adjusted for biological relevant covariates, in a cross-sectional study of 1142 HIV-infected patients.
Results: Increased suPAR levels were significantly associated with age, female sex, daily smoking, metabolic syndrome and waist circumference. cART was associated with 17% lower suPAR levels. In cART-treated patients 10-fold higher HIV RNA was associated with 15% higher suPAR, whereas there was no association in untreated patients. Patients with CD4+ cell count <350 cells/µL had higher suPAR levels than patients with CD4+ cell count ≥350 cells/µL , though not significantly. We found no association with nadir CD4+ cell count or with duration of HIV-infection [corrected]. Finally, suPAR was not associated with adipose tissue distribution, but strongly associated with low leg muscle mass [corrected].In patients infected through intravenous drug use (IDU), CD4+ cell counts ≥350 cells/µL were associated with 27% lower suPAR (p = 0.03), andsuPAR was 4% lower pr. year during treatment (p = 0.05); however, there was no association with HIV RNA, duration of HIV-infection, nor cART [corrected].
Conclusion: We found elevated suPAR levels in untreated patients compared to patients on cART. Moreover, we observed a significant positive association between suPAR and HIV RNA levels in cART-treated patients. Age, HIV-transmission through IDU, metabolic syndrome, smoking, and low leg muscle mass were also significantly associated with suPAR levels. Our study therefore indicates, that also other aspects of living with HIV than virologic and immunologic markers add to the increased inflammation in HIV-infected patients.