MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS) - OAR Sleep Supplement

摘要 本补充剂应用的目的是研究靶向犬尿氨酸(KYN)途径代谢物 由于客观测量习惯性睡眠和昼夜节律紊乱的分子机制增加了风险 并确定这些关系是否因生物学上的不同而不同 性行为和艾滋病毒疾病状况。我们将测量储存血浆中靶向KYN途径代谢物(n=800) 来自特征良好的MACS/WIHS联合队列研究(MWCCS)已经有习惯性睡眠的男性 通过一周的连续腕部动作记录仪(飞利浦)收集、验证和系统评分的测量结果 Respironics Actiwatch Spectrum Plus)。这将不会给MWCCS参与者和现场工作人员带来负担 副刊。到目前为止，还没有研究将KYN通路激活作为一种将睡眠和 对艾滋病毒相关和炎症介导的共病，如心脏代谢性疾病的昼夜节律干扰 在混合性别样本中，这也不是在所有艾滋病毒疾病状态中都有代表性的情况下实现的 两组(与未感染的对照组相比，艾滋病毒控制良好和控制较差)。结果将提供新颖的 对生物性行为和HIV疾病状态的洞察睡眠之间的机械关系的差异 和昼夜节律紊乱，KYN通路激活，以及HIV相关的心脏代谢性疾病，并提供 测试针对性睡眠和昼夜节律干预以降低感染艾滋病毒风险的坚实基础- 艾滋病毒老年男性和女性的相关合并症。

ABSTRACT The objective of this supplement application is to investigate targeted kynurenine (KYN) pathway metabolites as molecular mechanisms by which objectively measured habitual sleep and circadian disruption increase risk for HIV-associated cardiometabolic disease and to determine whether these relationships differ by biological sex and HIV disease status. We will measure targeted KYN pathway metabolites in stored plasma (n=800) from well characterized MACS/WIHS Combined Cohort Study (MWCCS) men who already have habitual sleep measures collected, validated, and systematically scored via one week continuous wrist actigraphy (Philips Respironics Actiwatch Spectrum Plus). There will be no MWCCS participant and field staff burden for this supplement. No study to date has examined KYN pathway activation as a mechanism linking sleep and circadian disruption to HIV-related and inflammatory mediated comorbidities such as cardiometabolic disease in a mixed sex sample nor has this been accomplished with representation across all HIV disease status groups (well and poorly controlled HIV with comparison to uninfected controls). Results will provide novel insights into biological sex and HIV disease status differences in the mechanistic relationships between sleep and circadian disruption, KYN pathway activation, and HIV-associated cardiometabolic disease and provide a strong foundation upon which to test targeted sleep and circadian interventions to reduce risk for HIV- associated comorbidities in men and women aging with HIV.