Cohort of HIV-Associated Seizures and Epilepsy in Zambia (CHASE): Scale up and expansion informed by R21 Findings

最近完成的由R21资助的艾滋病毒相关癫痫和癫痫队列研究(CHASE)， 招募95名患有艾滋病毒和新发癫痫的城市成年人，描述癫痫的病因，并提供 初步了解该人群中癫痫的发生率和危险因素。追逐 还检查了使用队列研究设计来确定与临床相关的后果的可行性 联合使用抗逆转录病毒药物(ARV)和酶诱导的抗癫痫药物(EI-AEDs) 撒哈拉以南非洲的大部分地区。大通R21的研究结果极大地促进了有限的 关于这一群体的文献，并为这一R01应用程序的设计提供了信息。在本次R01中，我们将继续 R21中描述的计划是将CHASE队列研究扩大到包括农村和儿科人群。 我们将再招收300名参与者(城市儿童、农村儿童和农村成年人各100名)，并如下 至少24个月，以确定反复发作和/或死亡的发生率。研究评估 确定不良结局的危险因素将包括常规脑脊液(CSF)评估、基线 神经精神病学筛查，脑脊液HIV病毒载量以及机会性感染的脑脊液聚合酶链式反应分析。 城市参与者将接受大脑核磁共振和脑电图检查，所有儿童将每季度接受一次检查。 神经发育评估。此外，一项对癫痫和艾滋病患者进行的暴露控制研究 将完成抗逆转录病毒药物和EI-AEDs，以评估这种常见药物组合是否会导致抗逆转录病毒病毒 爱滋病毒。Chikankata医院自2000年以来一直在那里提供服务，一个专门的癫痫护理小组将在那里提供服务 作为农村联合会的总部和暴露控制研究的研究地点。容量 建设活动将包括两名赞比亚初级学者(一名儿科医生和一名)的专业发展。 神经心理学家)，三名赞比亚核磁共振技术专家，大通银行授予管理人。此外，a 放射学方面的研究生住院医师培训课程将突出神经放射学部分 在美国、赞比亚和马拉维通过临床轮换建立。一名赞比亚医学院毕业生将 完成放射学实习，并在今年R01期间顺利进入赞比亚教职员工职位 在当地提供专业知识。这项工作将对以下人群的癫痫障碍的流行病学产生重要的见解 撒哈拉以南非洲大型国家的艾滋病毒携带者以及确定临床相关后果 联合使用抗逆转录病毒药物和IE-AEDs，从而为临床医生提供护理艾滋病毒+患者的 扣押，以及决定是否/何时启动AEDs所需的证据。Chase R01也将通知 政策制定者关于是否需要向需要双重治疗的人提供替代药物方案的问题 艾滋病毒和癫痫的治疗。最后，与R21资助的Chase努力一样，这项工作可能会找出 护理质量，为改善卫生服务以造福这一人群提供优先事项。

The recently completed, R21 funded, Cohort of HIV-Associated Seizures and Epilepsy (CHASE) Study, enrolled 95 urban adults with HIV and new onset seizure, delineated the seizure etiology, and provided preliminary insight into the incidence of and risk factors for epilepsy development in this population. CHASE also examined the feasibility of using a cohort study design to identify the clinically relevant consequences of combining antiretroviral medications (ARVs) and the enzyme-inducing antiepileptic drugs (EI-AEDs) used in most of sub-Saharan Africa. CHASE R21 study findings have significantly contributed to the limited body of literature on this population and have informed the design of this R01 application. In this R01, we will pursue the plan delineated in the R21 to expand the CHASE cohort study to include rural and pediatric populations. We will enroll 300 additional participants (100 each; urban children, rural children and rural adults) and follow them for at least 24 months to determine the incidence of recurrent seizure and/or death. Study assessments to identify risk factors for adverse outcomes will include routine cerebrospinal fluid (CSF) evaluations, baseline neuropsychiatric screening, and CSF HIV viral load as well as CSF PCR analyses for opportunistic infections. Brain MRIs and EEGs will be obtained in the urban participants and all children will undergo quarterly neurodevelopmental assessments. In addition, an exposure-control study of people with epilepsy and HIV on ARVs and EI-AEDs will be completed to assess whether this common drug combination leads to ARV resistant HIV. Chikankata Hospital, where a dedicated Epilepsy Care Team has provided services since 2000, will serve as the headquarters for the Rural Consortium and the study site for the exposure-control study. Capacity building activities will include professional development for two junior Zambian academics (a pediatrician and a neuropsychologist), three Zambian MRI technologists, and the CHASE grants administrators. In addition, a postgraduate residency training curriculum in Radiology with a prominent Neuroradiology component will be established through clinical rotations in the US, Zambia and Malawi. A Zambian medical school graduate will complete the Radiology Residency and segue seamlessly into a Zambian faculty position during this R01 to provide expertise locally. This work will yield critical insights into the epidemiology of seizure disorders among people with HIV in a large, sub-Saharan African country as well as identify the clinically relevant consequences of the co-usage of ARVs and IE-AEDS, thus providing clinicians caring for HIV+ individuals who experience a seizure with the evidence needed to decide whether/when to initiate AEDs. The CHASE R01 will also inform policy makers regarding the need (or not) to make alternative drug regimen available to people requiring dual treatment for HIV and epilepsy. Finally, as with the R21-funded CHASE efforts, this work may identify `gaps' in care quality that inform priorities for health service improvement to benefit this population.