Abstract
ObjectivesTo 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).MethodssuPAR 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.ResultsIncreased 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 21% higher suPAR, whereas there was no association in untreated patients. Patients with CD4+ cell count<350 cells/µL had 7% higher suPAR, but we found no association with nadir CD4+ cell count or with duration of HIV-infection. Finally, suPAR was not associated with adipose tissue distribution, but strongly associated with low muscle mass. In patients infected through intravenous drug use (IDU), CD4+ cell counts<350 cells/µL were associated with 27% lower suPAR (p = 0.03), and suPAR was 4% lower pr. year during treatment (p = 0.05); however, there was no association with HIV RNA, duration of HIV-infection, nor cART.ConclusionWe 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.
Highlights
Introduction of combination antiretroviral therapy has dramatically increased the lifespan of HIV-infected patients and decreased the prevalence of AIDS-related deaths [1]
We investigated whether HIV-related factors, demography, lifestyle and body composition were associated with inflammation measured by soluble urokinase plasminogen activator receptor (suPAR), thereby exploring mechanisms underlying the decreased life-time expectancy of HIV-infected patients
Metabolic syndrome could be assessed in 366 patients, and we found that patients with metabolic syndrome had 8% higher suPAR levels (p = 0.04) when adjusting for sex, age, European descent, and daily smoking
Summary
Introduction of combination antiretroviral therapy (cART) has dramatically increased the lifespan of HIV-infected patients and decreased the prevalence of AIDS-related deaths [1]. Several studies have reported higher prevalence of comorbidities such as cardiovascular disease (CVD), type 2 diabetes, and possibly cancer than in the general population [5,6,7]. Inflammation affects metabolism [12] and increased inflammation has been demonstrated to be a risk factor for CVD, type 2 diabetes, cancer and overall mortality in the general population [13]. HIV-infection causes chronic immune activation, and HIVinfected patients are characterised by higher inflammatory levels than non-HIV-infected individuals [14]. It has been proposed, that accelerated ageing characterises long term HIV-infection [15]
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