Abstract
BackgroundSystemic inflammation is a characteristic of both HIV-1 infection and aging (“inflammaging”). Intestinal epithelial barrier damage (IEBD) and microbial translocation (MT) contribute to HIV-associated inflammation, but their impact on inflammaging remains unclear.MethodsPlasma biomarkers for IEBD (iFABP), MT (LPS, sCD14), T-cell activation (sCD27), and inflammation (hsCRP, IL-6) were measured in 88 HIV-1 uninfected (HIVneg) and 83 treated, HIV-1-infected (HIVpos) adults from 20–100 years old.ResultsAge positively correlated with iFABP (r = 0.284, p = 0.008), sCD14 (r = 0.646, p = <0.0001) and LPS (r = 0.421, p = 0.0002) levels in HIVneg but not HIVpos subjects. Age also correlated with sCD27, hsCRP, and IL-6 levels regardless of HIV status. Middle-aged HIVpos subjects had elevated plasma biomarker levels similar to or greater than those of elderly HIVneg subjects with the exception of sCD14. Clustering analysis described an inflammaging phenotype (IP) based on iFABP, sCD14, sCD27, and hsCRP levels in HIVneg subjects over 60 years of age. The IP in HIVneg subjects was used to develop a classification model that was applied to HIVpos subjects to determine whether HIVpos subjects under 60 years of age were IP+. HIVpos IP+ subjects were similar in age to IP- subjects but had a greater risk of cardiovascular disease (CVD) based on Framingham risk score (p = 0.01).ConclusionsWe describe a novel IP that incorporates biomarkers of IEBD, MT, immune activation as well as inflammation. Application of this novel IP in HIV-infected subjects identified a group at higher risk of CVD.
Highlights
Inflammation increases in an age-associated manner termed inflammaging, which is characterized by increased plasma levels of pro-inflammatory cytokines (IL-6, IL-15, IL-8), coagulation factors (D-dimer), and acute phase reactants
To quantify Intestinal epithelial barrier damage (IEBD), microbial translocation (MT), and systemic inflammation we evaluated the plasma concentrations of intestinal fatty acid binding protein; LPS and sCD14; sCD27 (T cell activation); and hsCRP and IL-6
Consistent with previous reports [17,19,20,21,22], the geometric means of intestinal fatty acid binding protein (iFABP) (2.6x; 2.8x), sCD14 (1.2x; 1.3x), sCD27 (1.4x; 1.4x), and hsCRP (1.7x; 3.1x) were significantly elevated in the young adult and middle aged HIVpos subjects, respectively despite effective treatment with antiretroviral drugs (Fig. S3). This suggests that elevated levels of IEBD and MT markers associated with HIV infection could be masking more subtle age-associated changes
Summary
Consistent with previous reports [17,19,20,21,22], the geometric means of iFABP (2.6x; 2.8x), sCD14 (1.2x; 1.3x), sCD27 (1.4x; 1.4x), and hsCRP (1.7x; 3.1x) were significantly elevated in the young adult and middle aged HIVpos subjects, respectively despite effective treatment with antiretroviral drugs (Fig. S3) This suggests that elevated levels of IEBD and MT markers associated with HIV infection could be masking more subtle age-associated changes. The CMV IgG titer was significantly associated with both LPS (r = 0.260, p = 0.026) and sCD27 (r = 0.439, p , 0.0001) levels in the HIVpos subjects (data not shown) These results suggest that underlying coinfections could be contributing to the inflammaging phenotype in the HIVpos cohort.
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