Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis

Qibin Qi, Simin Hua, Clary B. Clish, Justin M. Scott, David B. Hanna, Tao Wang, Sabina A. Haberlen, Sanjiv J. Shah, Marshall J. Glesby, Jason M. Lazar, Robert D. Burk, Howard N. Hodis, Alan L. Landay, Wendy S. Post, Kathryn Anastos, Robert C. Kaplan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals. Methods Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV?) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque. Results After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P <.001), higher KYNA/TRP (P =.01), and similar kynurenic acid levels (P =.51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P <.001), while each SD increment in kynurenic acid (P =.02) and KYNA/TRP (P <.001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant. Conclusions Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalClinical Infectious Diseases
Volume67
Issue number2
DOIs
StatePublished - Jul 2 2018

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Keywords

  • HIV infection
  • association study
  • atherosclerosis
  • metabolite

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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