Impact of Obstructive Sleep Apnea and HIV on Ventricular Repolarization Lability

ABSTRACT In the era of successful combination antiretroviral therapy, human immunodeficiency virus (HIV) infection has shifted from a rapidly deteriorating disease to a manageable chronic condition with life expectancy similar to that of individuals without HIV. However, the prolonged lifespan has brought about an increase in comorbidities such as chronic obstructive pulmonary disease, type 2 diabetes, cardiovascular disease, and sudden cardiac death (SCD). Sleep disorders, particularly obstructive sleep apnea (OSA), are prevalent among those living with HIV, with recent data indicating a 47% higher prevalence in men with HIV compared to those without. OSA, characterized by upper airway collapse during sleep, is known to independently increase the risk of hypertension, cardiovascular disease, and cardiac arrhythmias, including SCD. Ventricular repolarization, a crucial aspect of cardiac electrophysiology, is destabilized by OSA-induced sympathetic nervous system activation, potentially leading to life-threatening arrhythmias. The QT variability index (QTVI), reflecting beat-to-beat QT interval fluctuations derived from the surface electrocardiogram (ECG), is a predictor of ventricular arrhythmias and SCD. Our preliminary data suggest that prevalent OSA is associated with increased ventricular repolarization lability (increased QTVI), and incident OSA exacerbates this lability. Given our previous findings from the Multicenter AIDS Cohort Study (MACS) of an increased QTVI in men with than without HIV, we aim to investigate the interaction between OSA and HIV on ventricular repolarization abnormalities. Our overarching goal is to delineate the independent and interactive effects of OSA and HIV on QTVI during sleep in a cohort of 851 men living with and without HIV. We hypothesize that OSA severity, measured by the apnea-hypopnea index (AHI), degree of nocturnal hypoxemia, and frequency of arousals, will be independently associated with higher QTVI. Furthermore, men with HIV are expected to exhibit higher QTVI than those without HIV, with OSA exacerbating the HIV-related increase in QTVI. Utilizing polysomnographic and ECG data from the MACS, we will employ multivariable regression models adjusted for relevant covariates to explore these associations. Anticipated results include independent associations between OSA severity, measures of hypoxemia and arousal frequency, and ventricular repolarization lability, along with a heightened repolarization lability in men with HIV. We expect OSA to augment the effects of HIV on repolarization lability, potentially increasing SCD risk. Given that OSA is pervasive in the HIV population, findings from the proposed analyses will have a fundamental impact on clinical practice by: (a) providing much-needed information on the pathogenesis of SCD risk in HIV, and (b) promoting early identification and treatment of OSA in those with HIV.