DESCRIPTION (provided by applicant): Antiretroviral (ARV) medications now allow persons living with HIV (PLWH) to age into late adulthood, although quality of life often remains impaired, in part due to development of chronic health problems. PLWH commonly report fatigue, insomnia, and poor sleep quality, though must studies of sleep in PLWH have been small, single-center studies. Obstructive sleep apnea (OSA) has not been well studied in PLWH, despite the increasing prevalence of OSA risk factors such as obesity and older age in PLWH. OSA and its associated intermittent nocturnal hypoxemia have also been associated with comorbidities commonly seen in PLWH, such as cardiovascular disease and cognitive impairment. Our preliminary data suggest that OSA is underdiagnosed in PLWH and that the presence of OSA is a strong predictor of fatigue symptoms. Although aging clearly increases OSA risk in the general population, the effect of aging on OSA risk in PLWH is unknown. Whether OSA and sleep fragmentation predict other clinical outcomes in PLWH, such as cognitive impairment, also remains unknown. Our study will address this knowledge gap by leveraging the ongoing Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) observational cohort study (NCT01737047) and quantify sleep in three groups of POPPY participants: PLWH >50 years of age (n=250), PLWH <50 years of age (n=125), and HIV negative controls >50 years of age (n=125). We will use wrist-worn, ambulatory overnight oximetry and actigraphy to characterize intermittent nocturnal hypoxemia, sleep efficiency, sleep duration, and other objective sleep measures. We will use questionnaires to assess patient-reported sleep outcomes. We will determine the prevalence of sleep abnormalities in older PLWH. We will also determine the relationships between objective sleep data, patient-reported sleep outcomes, and cognitive test performance, while leveraging the unique POPPY design to understand how aging and HIV affect such relationships. Lastly, we will determine how sleep abnormalities relate to immune activation, systemic inflammation, and endothelial dysfunction in PLWH. We have organized a multi- disciplinary team of experts in HIV-associated lung and breathing disorders, sleep epidemiology, HIV medicine, HIV translational science, and HIV epidemiology to implement this study. To our knowledge, our study will be the first to comprehensively characterize objective sleep data in PLWH, especially older PLWH, with adequate sample size, multi-site representation, and appropriate controls to determine how aging and HIV infection affect these measures. This cross-sectional study will inform the design of longitudinal cohort studies and future trials targeted at sleep interventions to improve quality of life and other clinical outcomes for PLWH.

PUBLIC HEALTH RELEVANCE: Persons living with HIV infection frequently report problems with their sleep. This study will take simple, yet precise, home-based measurements of sleep and determine: (1) how HIV and aging affect sleep, (2) how sleep affects brain function in HIV, and (3) how sleep affects inflammation in HIV.