# Impact of Poor Sleep on Inflammation and the Adenosine Signaling Pathway in HIV Infection

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $529,037

## Abstract

ABSTRACT
HIV infection, despite the development and implementation of antiretroviral therapy (ART), is associated with
high levels of inflammation, which appears to be a major factor underlying the elevated risk for premature
cardiovascular and pulmonary disease among people living with HIV. Recent work from our group identifies
impairments in the adenosine signaling pathway as an important mechanism leading to an inability to normally
regulate pro-inflammatory pathways. Adenosine signaling is also a key component to normal sleep-wake
regulation, with extracellular adenosine levels in the basal forebrain and other parts of the central nervous system
serving as the biochemical driver of the homeostatic drive for sleep. Chronically poor sleep, which is highly
prevalent among people living with HIV, has been demonstrated to alter adenosine signaling in the central nervous
system and acute sleep deprivation has been found to alter adenosine receptor expression in leukocytes.
Epidemiologic and experimental data suggest both acute and chronic disruption of normal sleep leads to elevated
inflammation and to many of the same downstream cardiopulmonary health consequences experienced by people
living with HIV. We have found self-reported poor sleep in an HIV(+) population is an independent predictor of
cardiopulmonary disease. In this proposal, we seek to test the hypothesis that one mechanism by which poor sleep
may impact inflammation and cardiopulmonary risk is via effects on peripheral adenosine signaling. We will
assess the association between objectively assessed sleep habits, inflammation and cardiopulmonary disease
markers in an ART-treated HIV(+) population and compare relationships with an HIV(-) control group. In the
setting of HIV infection, we will further compare levels of T-cell immune activation and peripheral adenosine
signaling in those with and without chronic sleep deprivation to assess the impact of chronic sleep habits on
adenosine signaling pathways among people living with HIV. Finally, we will assess the impact of 24 hours of
acute sleep deprivation on adenosine signaling, inflammation, immune activation, and endothelial function in an
HIV(+) population with healthy sleep habits to assess the impact of acute sleep loss on peripheral adenosine
signaling and downstream effects. In total, these experiments will evaluate the role of poor sleep on inflammation
and cardiopulmonary function in people living with HIV and evaluate the extent to which both acute sleep loss
and chronic sleep disruption impact inflammation and immune function in HIV and the role of defects in
peripheral adenosine signaling in mediating these effects. This work will provide insights regarding novel
therapeutic strategies towards preventing the long term cardiovascular and pulmonary complications of HIV
infection.

## Key facts

- **NIH application ID:** 9928985
- **Project number:** 5R01HL142118-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Bernard Jonas C Macatangay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $529,037
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928985

## Citation

> US National Institutes of Health, RePORTER application 9928985, Impact of Poor Sleep on Inflammation and the Adenosine Signaling Pathway in HIV Infection (5R01HL142118-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9928985. Licensed CC0.

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