Obstructive Sleep Apnea Endotypes and Impact on Phenotypes of People Living with HIV

项目摘要 艾滋病毒携带者可获得有效且普遍耐受性良好的抗逆转录病毒治疗 大大延长了寿命和预期寿命。在努力治疗疾病的同时 预防和治疗是必要的和正在进行的，现在一个重要的重点是了解 艾滋病毒携带者的症状和共病。例如，疲劳和困难 PLWH经常报告睡眠，即使在HIV被抑制和正常的情况下也是如此 CD4也算数。冠状动脉疾病、糖尿病和神经认知功能减退 被认为是艾滋病毒/抗逆转录病毒治疗的重要并发症。这些症状和合并症 阻塞性睡眠呼吸暂停(OSA)的症状和后果也可能是PLWH的重要因素。 OSA的定义是睡眠期间上呼吸道反复收缩，导致一过性 低氧血症和睡眠唤醒，并与所有心血管，代谢， 以及上面列出的神经认知后果。据报道，阻塞性睡眠呼吸暂停综合征的发病率高达70% 但很少被诊断出来，甚至更少(在一些队列中为4%)得到治疗。 阻塞性睡眠呼吸暂停综合征日益被认为是一种多因素障碍，可发生在不同的人 不同的原因，不仅是由于解剖学上的易感性(上呼吸道的塌陷性)， 但也与觉醒阈值低(太容易唤醒)、上呼吸道扩张器功能障碍有关 呼吸控制中的肌肉和不稳定性。通过仔细测量这些潜在的 因素和PLWH所经历的症状，这项建议试图理解 OSA潜在的不同机制-内型-导致不同的症状或 结果--PLWH中的表型。例如，阻塞性睡眠呼吸暂停综合征是否会导致疲劳 目前尚不清楚一名艾滋病毒携带者，或者这种疲劳感是否会随着阻塞性睡眠呼吸暂停综合症的治疗而改善。 我们的目标是： -了解OSA对PLWH重要症状的作用，例如 疲劳与心血管疾病 -比较不同OSA内型对PLWH表型的影响 -了解潜在的内型如何调节表型的变化 阻塞性睡眠呼吸暂停综合征的治疗

Project Summary The availability of effective and generally well-tolerated antiretroviral therapy for people with HIV has translated into dramatically longer survival and life expectancy. While efforts at disease prevention and cure are needed and ongoing, an important focus is now on understanding the symptoms and co-morbidities of people living with HIV (PLWH). For example, fatigue and difficulty sleeping are very commonly reported by PLWH even while HIV is suppressed and with normal CD4 counts. Coronary artery disease, diabetes mellitus and neurocognitive decline are now recognized as important complications of HIV/ART. These symptoms and co-morbidities important in PLWH may also be symptoms and consequences of obstructive sleep apnea (OSA). OSA is defined by repetitive collapse of the upper airway during sleep, which leads to transient hypoxemia and arousals from sleep, and is associated with all of the cardiovascular, metabolic, and neurocognitive consequences listed above. OSA has been reported to occur in up to 70% of PLWH, but few are diagnosed and even fewer (<4% in some cohorts) are treated. OSA is increasingly recognized as a multifactorial disorder that can occur in different people for different reasons, not only due to anatomical predisposition (collapsibility of the upper airway), but also related to low arousal threshold (wake up too easily), dysfunction in upper airway dilator muscles and instability in ventilatory control. Through careful measurement of these underlying factors and the symptoms experienced by PLWH, this proposal seeks to understand how different mechanisms underlying OSA – endotypes – lead to different symptoms or consequences – phenotypes – in PLWH. For example, whether OSA contributes to fatigue in an individual with HIV, or whether that fatigue will improve with treatment of OSA, is not known. Our goals are: - To understand the contribution of OSA to symptoms important for PLWH, such as fatigue and cardiovascular disease - To compare the impact of different OSA endotypes on phenotypes on PLWH - To understand how underlying endotype mediates changes in phenotype seen with treatment of OSA