Interaction Between Immune Activation, Sleep Disturbances and Circadian Timing on Cardiometabolic Risk in HIV Positive Patients

Abstract

Introduction South Africa still has the highest burden of Human Immunodeficiency Virus (HIV) in the world. Over the past 15 years, antiretroviral (ARV) treatments for HIV have improved, ensuring that people living with HIV (PLWH) have life expectancies like people living without HIV (PLWOH). Studies have shown that PLWH are at higher risk of death from cardiovascular disease than PLWOH. Poor sleep is a common issue for PLWH – treated and untreated. Poor sleep is a contributor to weight gain and higher BMI, contributing to the development of cardiometabolic disease. Poor sleep increases inflammation, contributing to the development of cardiovascular disease. Most studies investigating sleep in PLWH have been done in the northern hemisphere, which may not adequately represent South Africa. We test the hypotheses that: 1. PLWH in South Africa have poor sleep quality using validated tools, 2. Identify if the presence of HIV affects the homeostatic or circadian components of sleep, and 3. Identify if inflammation is present in PLWH with poor sleep. Methods: To assess the presence of poor sleep quality in participants at the Nthabiseng HIV Clinic at the Chris Hani Baragwanath Academic Hospital, Soweto (urban), we used the Pittsburgh Sleep Quality Index. To assess the impact of being HIV positive on sleep architecture and timing (circadian) in a study based in Agincourt (rural), Mpumalanga, we used actigraphy and dim light melatonin onset. To assess the presence of poor sleep in participants in Elandsdoorn (rural), Limpopo, we used one question from the Patient Health Questionnaire-9. We also investigated the relationship between the presence of poor sleep in PLWH and C-reactive protein. Results: We found poor sleep (Elandsdoorn, 1,040 PLWOH and 887 PLWH (691 treated), poor sleep quality (Soweto, N=139) and circadian misalignment (Agincourt, N=36) in PLWH. We found a positive correlation between poor sleep and inflammation in PLWH, and evidence that PLWH with poor sleep and elevated CRP had an increased risk for developing cardiometabolic disease. IMMUNE ACTIVATION, SLEEP AND CIRCADIAN TIMING IN HIV PATIENTS x Discussion and conclusion: Poor sleep is present in PLWH in South Africa, is associated with increased inflammation and could also be a contributor to increased cardiometabolic disease risk. Poor sleep in PLWH in South Africa needs to be investigated as a potential mediator of inflammation and cardiometabolic disease.