The IDOze Study: The Link Between Sleep Disruption and Tryptophan-Kynurenine Pathway Activation in Women With Human Immunodeficiency Virus

Author:

Rogando Andrea C12,Weber Kathleen M2,Xing Jiaqian3,Xue Xiaonan3,Yohannes Tsion2,Morack Ralph2,Qi Qibin3,Clish Clary4ORCID,Bullock Kevin4,Gustafson Deborah5,Anastos Kathryn6,Sharma Anjali6,Burgess Helen J7,French Audrey L8

Affiliation:

1. College of Science and Health at Charles R. Drew University of Medicine and Science , Los Angeles, California , USA

2. Hektoen Institute of Medicine/CORE Center of Cook County Health , Chicago, Illinois , USA

3. Department of Epidemiology and Population Health, Albert Einstein College of Medicine , Bronx, New York , USA

4. Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard , Cambridge, Massachusetts , USA

5. Department of Neurology, State University of New York Downstate Medical Center , Brooklyn, New York , USA

6. Department of Medicine, Albert Einstein College of Medicine , Bronx, New York , USA

7. Department of Psychiatry, University of Michigan , Ann Arbor, Michigan , USA

8. Department of Medicine, Stroger Hospital of Cook County Health , Chicago, Illinois , USA

Abstract

Abstract Background Poor sleep is associated with human immunodeficiency virus (HIV), particularly among women with HIV (WWH), although mechanisms are unclear. We explored cross-sectional associations between sleep disruption and tryptophan-kynurenine (T/K) pathway activation, measured by the kynurenine-to-tryptophan ratio (K:T). Methods HIV-uninfected women (HIV–) and WWH aged 35–70 years and on stable antiretroviral therapy were included. Sleep metrics were measured using wrist actigraphy. Plasma T/K pathway metabolites were measured using liquid chromatography–tandem mass spectrometry. Multivariate linear regression models examined relationships between K:T and actigraphy-based sleep metrics by HIV status. Results WWH (n = 153) and HIV– women (n = 151) were demographically similar. Among WWH, median CD4 was 751 cells/µL; 92% had undetectable HIV RNA. Compared to HIV– women, WWH had higher K:T (P < .001) and kynurenine (P = .01) levels but similar tryptophan levels (P = .25). Higher K:T was associated with more wake bouts (P = .001), more time awake after sleep onset (P = .01), and lower sleep efficiency (P = .03) in WWH only. Conclusions HIV infection was associated with T/K pathway activation; this activation was associated with poorer sleep efficiency and more fragmented sleep. While longitudinal studies are needed to elucidate the directionality of these associations, these findings may help identify treatments to reduce sleep disruption in WWH by targeting residual inflammation and T/K pathway activation.

Funder

National Heart, Lung, and Blood Institute

The Bronx

Brooklyn

Chicago Cook County

Multicenter AIDS Cohort Study

Women's Interagency HIV Study

Combined Cohort Study

NIH

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference50 articles.

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5. Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases;Song;Cell Mol Life Sci,2017

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