@article{b7136057a52246aa9a8cf5841deda5bc,
title = "Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis",
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.",
keywords = "HIV infection, association study, atherosclerosis, metabolite",
author = "Qibin Qi and Simin Hua and Clish, {Clary B.} and Scott, {Justin M.} and Hanna, {David B.} and Tao Wang and Haberlen, {Sabina A.} and Shah, {Sanjiv J.} and Glesby, {Marshall J.} and Lazar, {Jason M.} and Burk, {Robert D.} and Hodis, {Howard N.} and Landay, {Alan L.} and Post, {Wendy S.} and Kathryn Anastos and Kaplan, {Robert C.}",
note = "Funding Information: Financial support. This study was supported by the National Heart, Lung, and Blood Institute (NHLBI; K01HL129892 to Q. Q.). Other funding sources for this study were provided to Q. Q. (R01HL140976), R. C. K. (R01 HL126543, R01 HL132794, R01HL083760, R01HL095140), W. S. P. (R01-HL-095129), D.B. H. (K01-HL-137557), and Q. Q. (Feldstein Medical Foundation Research Grant). Funding Information: MACS (principal investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick; U01-AI35042); Northwestern University (Steven Wolinsky; U01-AI35039); University of California, Los Angeles (Roger Detels; U01-AI35040); University of Pittsburgh (Charles Rinaldo; U01-AI35041); and the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson; UM1-AI35043). The MACS is funded primarily by the NIAID at the NIH, with additional cofunding from the NCI. Targeted supplemental funding for specific projects was also provided by the NHLBI and the NIDCD. Support for MACS data collection was also provided to Johns Hopkins University CTSA (UL1-TR000424). Funding Information: WIHS (principal investigators): University of Alabama at Birmingham and University of Mississippi (Mirjam-Colette Kempf and Deborah Konkle-Parker; U01-AI-103401); Atlanta (Ighovwerha Ofotokun and Gina Wingood; U01-AI-103408); Bronx (Kathryn Anastos; U01-AI-035004); Brooklyn (Howard Minkoff and Deborah Gustafson; U01-AI-031834); Chicago (Mardge Cohen and Audrey French; U01-AI-034993); Metropolitan Washington (Seble Kassaye; U01-AI-034994); Miami (Margaret Fischl and Lisa Metsch; U01-AI-103397); UNC (Adaora Adimora; U01-AI-103390); Connie Wofsy Women{\textquoteright}s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien; U01-AI-034989); WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub; U01-AI-042590); and Southern California (Joel Milam; U01-HD-032632) (WIHS I–WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute (NCI), the National Institute on Drug Abuse, and the National Institute on Mental Health. Targeted supplemental funding for specific projects was also provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and Other Communication Disorders (NIDCD), and the NIH Office of Research on Women{\textquoteright}s Health. Support for WIHS data collection was also provided to University of California–San Francisco Clinical and Translational Science Awards (CTSA) (UL1-TR000004), Atlanta CTSA (UL1-TR000454), and University of North Carolina Center for AIDS Research (P30-AI-050410). Publisher Copyright: {\textcopyright} The Author(s) 2018. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",
year = "2018",
month = jul,
day = "2",
doi = "10.1093/cid/ciy053",
language = "English (US)",
volume = "67",
pages = "235--242",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "2",
}