Effects of HIV & HAART on Sleep & Daytime Function

艾滋病毒的影响

• 批准号: 7103540
• 负责人: PHILIP L SMITH
• 金额: $ 58.7万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103540
• 关键词: AIDS therapy; HIV envelope protein gp120; HIV infections; behavioral /social science research tag; cellular immunity; clinical research; disease /disorder proneness /risk; fatigue; functional ability; genetically modified animals; human subject; humoral immunity; hypoxia; interleukin 1; laboratory mouse; leptin; male; neuropsychology; obesity; patient oriented research; protease inhibitor; quality of life; respiratory airflow disorder; sleep apnea; sleep disorders; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): HIV is recognized as a devastating infection that leads to severe morbidity and earlier death. It is known that HIV infection is associated not only with disruptions in immune function but also in sleep with daytime fatigue, somnolence and impaired quality of life. Highly Active Anti-Retroviral Therapy (HAART) is now extending the life expectancy of those infected with HIV either allowing or producing chronic medical conditions and significant associated medical comorbidity. Our preliminary data indicate that both HIV infection and HAART are associated with substantial daytime fatigue. Moreover, HAART is also associated with sleep apnea, a known cause of sleep disruption and daytime somnolence. Our major hypothesis is that HIV infection, HAART, and associated alterations in humoral factors and cellular immunity lead to sleep disruption and sleep apnea, which both cause daytime dysfunction. In Specific Aim 1, we will elucidate the effects of HIV and HAART on nocturnal sleep architecture and daytime function. We hypothesize that HIV infection will be associated with sleep disruption and alterations in measures of daytime sleepiness, neurocognitive and neurobehavioral function, and quality of life. In Specific Aim 2, we will delineate the effects of HIV and HAART on the severity of upper airway obstruction and sleep. We hypothesize that HAART, but not HIV infection, is associated with an increased susceptibility for sleep apnea due to alterations in regional fat distribution and leptin. In Specific Aim 3, we will elucidate specific humoral and molecular pathways involved in the pathogenesis of upper airway, ventilatory and sleep/wake dysregulation. In this proposal, we capitalize on the well-established Baltimore site or the Multicenter Aids Cohort Study (MACS), a longitudinal study of HIV infection in gay men, to determine the impact of these factors on sleep quality, sleep apnea and daytime function. In a series of complementary murine studies, we further probe causal pathways involved in the pathogenesis of upper airway, respiratory and sleep/wake dysfunction. Conventional methods will be employed to assess sleep architecture, cellular immunity, humoral factors and daytime function, while novel analytic approaches will be used to quantify effects of HIV infection and therapy on sleep structure and upper airway function.

描述（由申请人提供）： 艾滋病毒被认为是一种毁灭性感染，会导致严重发病和过早死亡。 众所周知，艾滋病毒感染不仅与免疫功能受损有关，而且与睡眠相关，导致白天疲劳、嗜睡和生活质量受损。 高效抗逆转录病毒疗法 (HAART) 现在正在延长 HIV 感染者的预期寿命，从而导致或产生慢性疾病和严重的相关医疗合并症。 我们的初步数据表明，HIV 感染和高效抗逆转录病毒治疗 (HAART) 都与白天的严重疲劳有关。 此外，HAART 还与睡眠呼吸暂停有关，睡眠呼吸暂停是睡眠中断和白天嗜睡的已知原因。 我们的主要假设是，HIV 感染、HAART 以及相关的体液因子和细胞免疫的改变会导致睡眠中断和睡眠呼吸暂停，这两者都会导致日间功能障碍。 在具体目标 1 中，我们将阐明 HIV 和 HAART 对夜间睡眠结构和日间功能的影响。 我们假设艾滋病毒感染与睡眠中断以及日间嗜睡、神经认知和神经行为功能以及生活质量的改变有关。 在具体目标 2 中，我们将描述 HIV 和 HAART 对上呼吸道阻塞和睡眠严重程度的影响。 我们假设，由于局部脂肪分布和瘦素的改变，HAART（而非 HIV 感染）与睡眠呼吸暂停易感性增加相关。在具体目标 3 中，我们将阐明参与上呼吸道、通气和睡眠/觉醒失调发病机制的特定体液和分子途径。 在本提案中，我们利用成熟的巴尔的摩站点或多中心艾滋病队列研究 (MACS)（一项针对男同性恋者 HIV 感染的纵向研究）来确定这些因素对睡眠质量、睡眠呼吸暂停和日间功能的影响。 在一系列补充性小鼠研究中，我们进一步探讨了上呼吸道、呼吸和睡眠/觉醒功能障碍发病机制中涉及的因果途径。 传统方法将用于评估睡眠结构、细胞免疫、体液因素和日间功能，而新颖的分析方法将用于量化 HIV 感染和治疗对睡眠结构和上呼吸道功能的影响。