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

项目摘要 中风是世界范围内第二大死亡原因和第一大残疾原因， (PWH)与未感染艾滋病毒（HIV-）的个体相比，中风的风险增加了一倍以上。撒哈拉以南 非洲（SSA）承担着最大的中风负担，因为它也是全球约2/3 在高危人群中，艾滋病毒可能是造成这一负担的主要原因。然而，导致 PWH中的过度中风风险尚未得到充分了解，因此，预防中风的最佳方法 在威尔斯亲王医院之间的关系并不成立。我们假设维生素D缺乏症（VDD）可能参与了 PWH中风的发病机制。VDD在PWH中比HIV人群更常见，可能会加重 抗逆转录病毒疗法（ART），并在SSA中非常普遍。关于是否存在 VDD在HIV人群中易患中风。然而，由于艾滋病毒感染和VDD都导致 内皮功能障碍，然后可能导致中风，我们假设VDD和HIV感染， 协同作用，增加PWH中中风的风险。 在这个提议中，我们试图证明VDD是HIV感染、内皮细胞和细胞因子之间的机制联系。 功能障碍和缺血性卒中。我们将利用发展神经病学临床和研究能力 在赞比亚与来自美国的更高级的调查人员合作， 假说.为了做到这一点，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：ART治疗的PWH伴缺血性卒中;和（2）对照：ART- 接受治疗的PWH无卒中。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， 包括细胞内粘附分子-1、血管细胞粘附分子-1和C反应蛋白。 如果VDD与PWH中的卒中相关，则本研究将提供必要的初步数据， 随后，对补充维生素D预防中风进行了大规模多国临床试验， PWH。如果成功的话，维生素D可能会提供一种相对便宜和可扩展的干预措施，以预防中风， 世界各地的PWH越来越受到关注，特别是在接受抗逆转录病毒治疗的艾滋病毒感染者中。

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.