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

项目摘要 为艾滋病毒感染者提供有效和普遍耐受良好的抗逆转录病毒疗法 已经转化为显著更长的生存和预期寿命。虽然在疾病方面的努力 预防和治疗是需要的，也是正在进行的，现在的一个重要重点是了解 艾滋病毒感染者（PLWH）的症状和并发症。例如，疲劳和困难 睡眠是非常常见的报告PLWH，即使艾滋病毒受到抑制，并与正常 CD 4计数。冠状动脉疾病、糖尿病和神经认知能力下降现在 被认为是艾滋病毒/抗逆转录病毒疗法的重要并发症。这些症状和合并症 在PLWH中重要的还可能是阻塞性睡眠呼吸暂停（OSA）的症状和后果。 阻塞性睡眠呼吸暂停是指睡眠期间上呼吸道的反复塌陷， 低氧血症和睡眠觉醒，并与所有的心血管，代谢， 和神经认知后果。据报道，OSA的发生率高达70%。 但很少有人被诊断出来，甚至更少（在一些队列中<4%）得到治疗。 OSA越来越被认为是一种多因素的疾病，可以发生在不同的人， 不同的原因，不仅是由于解剖学上的倾向（上气道的可扩张性）， 但也与低唤醒阈值（太容易醒来）、上气道扩张器功能障碍有关 肌肉和不稳定性的控制。通过仔细测量这些潜在的 因素和症状经历的PLWH，这项建议旨在了解如何 不同的机制导致不同的症状， 结果-表型-在PLWH。例如，OSA是否有助于疲劳， 艾滋病病毒感染者的疲劳，或者这种疲劳是否会通过治疗OSA而改善，目前尚不清楚。 我们的目标是： - 了解阻塞性睡眠呼吸暂停对PLWH重要症状的影响，例如 疲劳与心血管疾病 - 比较不同OSA内型对PLWH表型的影响 - 为了了解潜在的内型如何介导表型的变化， 治疗OSA

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