Poor Sleep and Inflammation in HIV-Infected Adults
Condition: HIV-1-infection; Sleep Deprivation; Inflammation
MeSH terms: Infections; Sleep Deprivation; Inflammation
Study type: Interventional

Summary: 
      People living with HIV (PLWH) often have poor sleep, which may put them at a higher risk for
      many chronic diseases, including cardiovascular disease. One of the mechanisms by which this
      may occur is via chronic inflammation and endothelial dysfunction. Adenosine plays an
      important role in sleep homeostasis, with levels increasing in the CSF in response to sleep
      deprivation and falling with sleep. Peripherally, adenosine, via its signaling pathway, plays
      an important role in immunoregulation by suppressing the inflammatory response. PLWH, even on
      antiretroviral therapy, have suppressed peripheral adenosine levels which are predictive of
      adverse cardiovascular outcomes. The hypothesis underlying this study is that acute sleep
      deprivation in PLWH does not result in a compensatory increase in extracellular adenosine and
      its signaling peripherally, and this failure to appropriately compensate, leads to an
      increase in systemic inflammation and endothelial dysfunction.
    

Detailed description: 
      People living with HIV infection (PLWH) are known to be at higher risk of cardiovascular
      disease and also have a higher prevalence of poor sleep than people who do not have HIV
      infection. Understanding the underlying mechanisms for the elevated risk of cardiovascular
      disease in PLWH is important to developing novel strategies to mitigate this risk. Poor sleep
      has been postulated to mediate some of the elevated cardiovascular risk in PLWH given the
      high prevalence of poor sleep in PLWH and the epidemiologic association of poor sleep with
      adverse cardiovascular outcomes among people who do not have HIV infection. However, the
      mechanisms by which PLWH may be more sensitive to sleep loss from a cardiovascular standpoint
      are unclear. One potential explanation for any elevated sensitivity would be via alterations
      in the adenosine signaling pathway.

      Changes in extracellular adenosine levels in the brain and central nervous system play an
      important homeostatic role in sleep-wake regulation. Sleep deprivation results in a rise in
      extracellular adenosine levels while sleep itself leads to a rapid decline in levels.
      Peripheral adenosine signaling is a central feature of immunoregulation, primarily through
      its effects on inflammatory cytokine expression and lymphocyte adenosine receptor expression.
      PLWH tend to have a suppressed level of peripheral adenosine signaling and this level of
      suppression predicts risk of cardiovascular disease. The purpose of this study is to explore
      the impact of acute sleep deprivation among PLWH on measures of inflammation and endothelial
      function and to assess the extent to which any changes may be explained by alterations in
      peripheral adenosine signaling.

      The study will enroll 40 PLWH, age 18-75, who have been on ART for greater than 48 weeks.
      Screening with questionnaires, actigraphy and polysomnography will eliminate individuals with
      underlying chronic sleep abnormalities. A prior night of polysomnography in the sleep lab
      will also habituate subjects to sleeping while monitored in the sleep lab.

      Participants will arrive in the sleep laboratory in the evening and be allowed to sleep for 8
      hours timed to their usual sleep patterns. On waking, participants will provide a urine
      sample that will be assayed for adenosine and adenosine metabolites. Blood will be drawn to
      measure markers of inflammation as well as markers of activation of the peripheral adenosine
      signaling system. Endothelial function will be assessed using flow mediated dilation.

      Participants will be kept awake for the subsequent 24 hours including the 8 hour normal sleep
      period. On the second morning, subjects will again provide urine and blood samples for the
      same bioassays described above and then undergo repeat assessment of endothelial function.
    

Intervention name(s): Sleep deprivation
Intervention type(s): Behavioral
Intervention description(s): Eight hour opportunity for sleep followed by 24 hours of sleep deprivation.
Intervention model: Single Group Assignment
Intervention model description: All participants will undergo one night of normal sleep (Night 1) followed by a subsequent night (Night 2) of sleep deprivation. Outcomes will be assessed the morning (Day 1 and Day 2) after each condition.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: adenosine