Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis

Clin Infect Dis. 2018 Jul 2;67(2):235-242. doi: 10.1093/cid/ciy053.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Carotid Arteries / pathology
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / complications
  • Disease Progression*
  • Female
  • HIV Infections / complications*
  • Humans
  • Kynurenine / blood*
  • Kynurenine / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Tryptophan / blood*
  • Tryptophan / metabolism


  • Biomarkers
  • Kynurenine
  • Tryptophan