Treating insomnia to reduce inflammation in HIV

项目摘要 严重非艾滋病事件（SNAE），包括肺气肿、糖尿病、骨质疏松症、心血管疾病和 认知障碍已成为艾滋病毒相关发病率和死亡率的重要因素。SNAE 可能是由全身性炎症引起的，与HIV感染者（PWH）相比， 艾滋病毒阴性者，尽管病毒学抑制。具体而言，全身性炎症的循环标志物升高 炎症[高敏C反应蛋白（hsCRP）、白细胞介素-6（IL-6）]和单核细胞证据 活化[sCD 14、sCD 163、CD 14 + CD 16+中间单核细胞]与SNAE的风险更高相关。 胰岛素是一般人群健康状况不佳的已知风险因素，可能与以下因素有关： 更严重的全身性炎症。幸运的是，失眠是可以改变的，而且明确的一线治疗方法已经 鉴定2016年美国医师学会指南得出结论， 成人慢性失眠症不是药物治疗，而是失眠症的CBT（CBT-I），考虑到强大的 证据表明它是安全的，有效的，广泛适用的持久利益。一个可行而有效的互联网 CBT-I工具称为睡眠健康使用互联网（SHUTi）的开发和验证本应用程序的 顾问李·里特班德博士在多项随机对照试验中，舒体已被证明对治疗失眠有效， 一般人口。据我们所知，互联网CBT-I在PWH以前没有被研究过。所以我们 该提案代表了在新患者中已建立的干预技术的创新应用 人口本申请的中心目的是评估SHUTI减少全身性 炎症，特别是PWH中的单核细胞活化。我们将通过解决以下问题来实现这一目标： 以下具体目的：评估失眠症认知行为疗法（CBT-I）对 病毒学抑制的HIV阳性成人失眠症患者的全身炎症指标。我们 将进行一项单中心II期RCT，比较SHUTi与接受睡眠的活性对照组 50例病毒学抑制性PWH伴失眠症患者卫生教育计划以减少生物标志物 炎症和单核细胞活化的影响。积极的第二阶段试验将提供概念验证数据， 需要进行效应量估计，以证明和适当设计多中心III期RCT，以建立长期 SHUTi（一种实用且易于扩展的干预措施）对HIV相关炎症和预防 SNAE。

PROJECT ABSTRACT Serious non-AIDS events (SNAE), including emphysema, diabetes, osteoporosis, cardiovascular disease, and cognitive impairment, have emerged as important contributors to HIV-related morbidity and mortality. SNAE are likely driven by systemic inflammation, which remains heightened in people with HIV (PWH), compared to HIV-negative persons, despite virologic suppression. Specifically, elevated circulating markers of systemic inflammation [high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6)] and evidence of monocyte activation [sCD14, sCD163, CD14+CD16+ intermediate monocytes] are associated with greater risks of SNAE. Insomnia is a known risk factor for poor health outcomes in the general population, perhaps via its link with greater systemic inflammation. Fortunately, insomnia is modifiable, and the clear first-line treatment has been identified. The 2016 American College of Physicians guideline concluded that the preferred treatment for chronic insomnia in adults is not pharmacologic therapy but rather CBT for insomnia (CBT-I), given the strong evidence that it is safe, effective, and broadly applicable with durable benefits. A feasible and effective internet CBT-I tool called Sleep Healthy Using The Internet (SHUTi) was developed and validated by this application’s consultant, Dr. Lee Ritterband. In multiple RCTs, SHUTi has proven effective for treating insomnia in the general population. To our knowledge, internet CBT-I in PWH has not previously been studied. Thus, our proposal represents an innovative application of an established intervention technology in a new patient population. The central objective of this application is to evaluate SHUTI’s ability to reduce systemic inflammation, and, in particular, monocyte activation in PWH. We will meet this objective by addressing the following Specific Aim: To evaluate the effects of cognitive-behavioral therapy for insomnia (CBT-I) on measures of systemic inflammation in virologically-suppressed, HIV-positive adults with insomnia disorder. We will conduct a single-site, phase II RCT comparing SHUTi to an Active Comparator group receiving sleep hygiene education program in 50 virologically-suppressed PWH with insomnia disorder to reduce biomarkers of inflammation and monocyte activation. A positive phase II trial would provide the proof-of-concept data and effect size estimates needed to justify and properly design a multisite, phase III RCT to establish the long-term effects of SHUTi (a practical and readily scalable intervention) on HIV-related inflammation and prevention of SNAE.