Abstract
Sleep disturbances are prevalent in women with HIV (WWH). Tryptophan-kynurenine (T-K) pathway metabolites are associated with alterations in actigraphy derived sleep measures in WWH, although may not always correlate with functional impairment. We investigated the relationship between T-K pathway metabolites and self-reported daytime dysfunction in WWH and women without HIV (WWoH). 141 WWH on stable antiretroviral therapy and 140 demographically similar WWoH enrolled in the IDOze Study had targeted plasma T-K metabolites measured using liquid chromatography-tandem mass spectrometry. We utilized the daytime dysfunction component of the Pittsburgh Sleep Quality Index (PSQI) to assess functional impairment across HIV-serostatus. Lower levels of 5-hydroxytryptophan and serotonin were associated with greater daytime dysfunction in all women. In WWH, daytime dysfunction was associated with increased kynurenic acid (R = 0.26, p < 0.05), and kynurenic acid-tryptophan (KA-T) ratio (R = 0.28, p < 0.01). WWH with daytime dysfunction had a 0.7 log fold increase in kynurenic acid compared to WWH without daytime dysfunction. Kynurenic acid levels and the KA-T ratio were associated with daytime dysfunction in WWH but not in WWoH. Longitudinal studies are needed to establish a causal relationship and directionality between T-K metabolic changes and sleep impairment in WWH.
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Acknowledgements
The authors thank the study participants and the staff at the MWCCS sites.
Funding
The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). The work in this manuscript was primarily funded by the National Heart, Lung, and Blood Institute (R01HL142116; MPIs: Audrey French, Helen Burgess) with additional co-funding for retrospective data collection from the following Women’s Interagency HIV Study (WIHS) clinical research sites (now the MACS/WIHS Combined Cohort Study (MWCCS): Chicago Cook County (U01-HL146245, MPIs: Mardge Cohen, Audrey French); Bronx (U01-HL146204, MPIs: Kathryn Anastos, Anjali Sharma), and Brooklyn (U01-HL146202 MPIs: Deborah Gustafson, Tracey Wilson). The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). The authors gratefully acknowledge the contributions of the study participants and dedication of the staff at the MWCCS sites. This work was also in part funded by the JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN; P30 MH075673).
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Study conceptualization and design: A.F., K.W., R.D., L.R: Patient enrollment and data collection: A.F., A.S., D.G., R.M., T.Y. Metabolomics on plasma samples: C.C., K.B. Wrote the main text and performed analysis: E.S. Provided expert analysis: A.F., K.W., R.D, L.R., E.S., E.D. Critical editing and review: A.R., D.G., A.S., E.D., Q.Q.
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The study was performed according to the principles outlined by the Helsinki Declaration. All participants provided informed consent in accordance with Department of Health and Human Services guidelines and with approval from each site’s institutional review board: Chicago– Cook County Health IRB #18 − 008; Brooklyn– SUNY Downtown state Health Sciences University IRB and Privacy Board #1280378-8; Bronx– Albert Einstein College of Medicine IRB #2018–9115.
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Shorer, E.F., Rubin, L.H., French, A.L. et al. Tryptophan-kynurenine metabolic pathway and daytime dysfunction in women with HIV. J. Neurovirol. (2024). https://doi.org/10.1007/s13365-024-01195-x
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DOI: https://doi.org/10.1007/s13365-024-01195-x