Contribution of intestinal barrier damage, microbial translocation and HIV-1 infection status to an inflammaging signature

Abstract

Background: Systemic 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. Methods: Plasma biomarkers for IEBD (iFABP), MT (LPS, sCD14), T-cell activation (sCD27), and inflammation (hsCRP, IL-6) were measured in 88 HIV-1 uninfected (HIV neg) and 83 treated, HIV-1-infected (HIVpos) adults from 20-100 years old. Results: Age 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+. HIV pos 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). Conclusions: We 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. © 2014 Steele et al.