? DESCRIPTION (provided by applicant): Unprecedented progress has been made in the treatment and management of HIV-1 infection, profoundly reducing the mortality rate amongst HIV-1-seropositive individuals. However, with increased survival new clinical challenges are emerging in this population, particularly the prevention and treatment of cardiovascular disease (CVD) in middle-aged and older adults with HIV-1. People with HIV-1 infection represent one of the most rapidly growing aging cohorts. Individuals aged 50 years and older account for approximately 30% of the 1.2 million people living with HIV-1 in the United States. With HIV-1-seropositive adults living longer, CVD and its related pathologies are heightened by advancing age further complicating the care of these individuals and imposing enormous human and financial burden. Despite an improved understanding of many of the pathologic consequences associated with HIV-1 infection, factors associated with aging that contribute to an enhanced rate of atherothrombotic vascular disease with HIV-1 are poorly understood. It has become apparent that the increased incidence of CVD in older HIV-1-seropositive individuals is not solely due to age-related worsening of traditional CVD risk factors, but also involves ill-defined factors. Poor sleep quality and quantity is now a recognized problem within the HIV-1 population, and is most prominent in older seropositive adults. More than 70% of HIV-1-infected adults report sleep problems that confer negative consequences for cardiovascular health, disease burden and quality of life. One of the most common sleep problems is habitual short sleep duration. While the behavioral and cognitive consequences of this reduced sleep time are well documented, mounting evidence suggests that insufficient sleep is also associated with increased cardiovascular morbidity and mortality. The specific aims of the present proposal are to determine: 1) the influence of chronic insufficient sleep on endothelium-dependent nitric oxide-mediated vasodilation in ART-treated older HIV-1-seropositive adults; 2) the influence of chronic insufficient sleep on the capacity of the vascular endothelium to release tissue-type plasminogen activator (t-PA) in ART-treated older HIV-1-seropositive adults; and 3) if individualized targeted sleep interventions that increase sleep duration and enhance sleep quality improve vascular endothelium-dependent nitric oxide-mediated vasodilation and endothelial t-PA release in ART-treated older HIV-1-seropositive adults. To address these aims, 120 ART-treated HIV-1-seropositive adults, ranging in age from 50-75 years will be studied. Endothelium-dependent vasodilation and endothelial t-PA will be assessed, in vivo, using an isolated forearm model. The results of the proposed study will provide new and clinically important information regarding the influence of insufficient sleep and the effects of targeting sleep as a therapeutic modality on vascular endothelial function in older ART-treated HIV-1-seropositive adults.

R01HL131458

2016-01-15

2020-12-31