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Advanced Glycation End Products Are Associated With Inflammation and Endothelial Dysfunction in HIV

El Kamari, Vanessa, MDa,b; Thomas, Alicia, MSb; Shan, Lingpeng, MSa; Sattar, Abdus, PhDa; Monnier, Vincent, MDa; Howell, Scott K., MSc; Beisswenger, Paul J., MDc; McComsey, Grace A., MDa,b

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1, 2019 - Volume 81 - Issue 2 - p e55–e62
doi: 10.1097/QAI.0000000000002030
Translational Research
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Objective: To compare levels of advanced glycation end products (AGEs) between HIV-infected patients and uninfected controls and assess the relationship between AGEs, HIV, inflammation, and endothelial dysfunction.

Design: Cross-sectional study involving 90 individuals (68 HIV+ and 22 healthy controls matched by age and sex).

Methods: AGE levels were assessed using 3 different modalities: free AGEs were measured in the serum, skin autofluorescence (AF) was determined with a noninvasive reader, and dietary AGEs were estimated using 24-hour dietary recalls. Markers of inflammation, immune activation, and endothelial dysfunction were also measured. Wilcoxon rank-sum and χ2 tests were used to compare AGEs between groups. Spearman correlations were used to explore relationships between variables while adjusting for different covariates.

Results: Overall, 71% were men and 68% were African American, with a median age of 53 years. Among HIV-infected individuals, all participants were on antiretroviral therapy by design, and most participants (78%) had an undetectable HIV-1 RNA level (≤20 copies/mL). Skin AF and serum AGEs were significantly higher in HIV-infected participants compared with uninfected controls (P < 0.01), whereas no differences in dietary AGEs were found between groups (P = 0.2). In the HIV-infected group, but not in controls, skin AF and circulating AGEs were significantly associated with inflammatory and oxidative markers, and with markers of endothelial dysfunction.

Conclusions: These results suggest intrinsic production of AGE in HIV-infected individuals. The relationship between serum/skin AGE and inflammatory, oxidative, and cardiovascular markers highlights the potential implications of AGEs in chronic inflammation and endothelial dysfunction in HIV, suggesting a new potential target for HIV-associated heightened inflammation and cardiovascular risk.

aCase Western Reserve University, Cleveland, OH;

bUniversity Hospitals Cleveland Medical Center, Cleveland, OH; and

cGeisel School of Medicine at Dartmouth, Prevent AGE Healthcare LLC, Lebanon, NH.

Correspondence to: Grace A. McComsey, MD, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106 (e-mail: grace.mccomsey@uhhospitals.org).

G.A.M. received Grant support to her institution from BMS, Roche, Merck, Astellas, and Gilead.

G.A.M. has served as consultant for Gilead, Merck, and ViiV/GSK. P.B. has received compensation for mass Spec Analyses. The remaining authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received January 15, 2019

Accepted February 25, 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.