Abstract Introduction Poor sleep increases peripheral inflammation, but the underlying mechanism is unclear. Extracellular adenosine (ADO) metabolism occurs via ectoenzyme CD39 and CD73 activity, and dysregulated purinergic metabolism contributes to HIV-associated inflammation. Sleep affects ADO metabolism in the central nervous system, but its effects on peripheral ADO metabolism have been understudied. We sought to evaluate how peripheral ADO metabolism differs by sleep metrics in people with HIV (PWH) and without HIV (PWOH). Methods Virally suppressed PWH with CD4+ count 350 cells/mm3 on stable antiretroviral therapy for 1 year and age- and sex-matched PWOH underwent 14 days of wrist actigraphy. Sleep duration, efficiency, midpoint, and regularity (standard deviation of midpoint) were derived. Blood samples were analyzed by flow cytometry to determine the percentage of T cells expressing one or both purinergic ectoenzymes (CD39 and CD73). Multivariable linear regressions adjusted for age, sex at birth, race, body mass index, and smoking status. Results Participants (94 PWH and 87 PWOH) had a mean±SD age of 56 ±11 years and 25% were female. The median (IQR) CD4+ count among PLWH was 763 (578, 982 cells/mm3). Every hour decrease in sleep duration was associated with (mean±SE) 4.1±1.8% fewer CD39+CD8+ T-lymphocytes in PLWH (p=0.03) but no association in PWOH (2.4±2.6%, p=0.35). Among PWOH, every hour increase in standard deviation of midpoint was associated with 6.9±3.4% fewer CD39+CD4+(p 0.05) and 6.5±3.3% fewer CD39+CD8+ (p= 0.05) T-lymphocytes. In contrast, there was no association between regularity and CD39+ positivity in CD4+ (1.4±2.0%, p=0.48) or CD8+ (1.3±1.9%, p=0.52) T-cells among PWH. Neither sleep efficiency nor midpoint were associated with purinergic ectoenzyme expression in PWH or PWOH. Conclusion We identified sleep duration was associated with peripheral ADO metabolism in PWH while sleep regularity was associated with peripheral ADO metabolism in PWOH. Future research should investigate if sleep-based interventions, such as sleep extension, improves peripheral adenosine metabolism by in PWH. Support (if any) This study was supported by R01HL142118 and the AASM Physician-Scientist Training Award.
Borker et al. (Fri,) studied this question.