Adaptation and Implementation of Clinical Practice Guidelines to Improve Stroke Outcomes in Zambia

项目总结 中风是世界范围内第二大死亡原因和主要残疾原因，艾滋病毒携带者 与未感染艾滋病毒(HIV-)的人相比，PWH患者患中风的风险是前者的两倍多。撒哈拉以南地区 非洲(SSA)承担着中风的最大负担，因为它也是全球约三分之二的 在威尔斯亲王医院的人口中，艾滋病毒很可能对这一负担起到很大作用。然而，导致这些问题的机制 PWH中额外的中风风险尚未得到很好的了解，因此，预防中风的最佳方法 在威尔斯亲王医院中没有设立。我们推测维生素D缺乏(VDD)可能与 慢性阻塞性肺疾病卒中的病因。VDD在PWH人群中比HIV人群中更常见，可能会加剧 通过抗逆转录病毒治疗(ART)，并且在SSA中高度流行。有相互矛盾的证据表明 VDD在HIV人群中易患中风。然而，因为艾滋病毒感染和VDD都会导致 可能导致中风的内皮功能障碍，我们假设VDD和HIV感染 协同作用可增加PWH患者发生中风的风险。 在这项提议中，我们试图证明VDD是HIV感染、内皮细胞之间的一种机制联系 SSA中的功能障碍和缺血性卒中。我们将利用不断发展的神经学临床和研究能力 在赞比亚与来自美国的更多高级调查人员合作，严格测试 假设。为此，我们将在大学教学医院(UTH)进行病例对照研究 在赞比亚卢萨卡，包括(1)病例：接受抗逆转录病毒治疗的先心病合并缺血性中风；(2)对照：抗逆转录病毒治疗- 治疗后PWH未发生卒中。参与者将接受临床和人口统计学评估，血液将 收集用于测定25-羟基维生素D水平和内皮功能障碍的生物标志物， 包括细胞间黏附分子-1、血管细胞黏附分子-1和C反应蛋白。 如果VDD与PWH中的卒中有关，这项研究将提供必要的初步数据 随后进行的维生素D补充用于初级中风预防的大规模跨国临床试验 威尔斯亲王医院。如果成功，维生素D可能会提供一种相对廉价和可扩展的干预措施来预防中风 在全世界范围内，这是一个日益令人担忧的问题，特别是在接受抗逆转录病毒治疗的艾滋病毒老年患者中。

PROJECT SUMMARY Stroke is the second leading cause of death and leading cause of disability worldwide, and people with HIV (PWH) are at more than double the risk of stroke compared to HIV-uninfected (HIV-) individuals. Sub-Saharan Africa (SSA) shoulders the greatest burden of stroke and, because it’s also home to ~2/3 of the global population of PWH, HIV likely substantially contributes to this burden. However, the mechanisms leading to excess stroke risk amongst PWH are not well-understood and, therefore, optimal ways to prevent stroke amongst PWH are not established. We hypothesize that vitamin D deficiency (VDD) may be involved in the etiopathogenesis of stroke in PWH. VDD is more common in PWH than HIV- populations, can be exacerbated by antiretroviral therapy (ART), and is highly prevalent in SSA. There is conflicting evidence about whether VDD predisposes to stroke in HIV- populations. However, because both HIV infection and VDD lead to endothelial dysfunction which may then result in stroke, we hypothesize that VDD and HIV infection synergistically interact to increase the risk of stroke among PWH. In this proposal, we seek to demonstrate that VDD is a mechanistic link between HIV infection, endothelial dysfunction, and ischemic stroke in SSA. We will leverage developing neurology clinical and research capacity in Zambia in collaboration with more senior investigators from the United States to rigorously test this hypothesis. In order to do this, we will conduct a case-control study at the University Teaching Hospital (UTH) in Lusaka, Zambia consisting of (1) cases: ART-treated PWH with ischemic strokes; and (2) controls: ART- treated PWH without stroke. Participants will undergo clinical and demographic assessments, and blood will be collected for determination of 25-hydroxyvitamin D level and biomarkers of endothelial dysfunction, including intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and C reactive protein. If VDD is associated with stroke in PWH, this research will provide the preliminary data necessary for a subsequent large-scale, multinational clinical trial of vitamin D supplementation for primary stroke prevention in PWH. If successful, vitamin D may offer a relatively inexpensive and scalable intervention to prevent strokes in PWH across the world, an increasing concern especially amongst ART-treated people aging with HIV.