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

 描述(由申请人提供)：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)，招募了95名患有艾滋病毒和新发癫痫的城市成年人，描绘了癫痫的病因，并对这一人群中癫痫的发生率和危险因素提供了初步的见解。Chase还研究了使用队列研究设计来确定在撒哈拉以南非洲大部分地区使用的抗逆转录病毒药物(ARV)和酶诱导抗癫痫药物(EI-AEDs)联合使用的临床相关后果的可行性。大通R21的研究结果大大促进了关于这一群体的有限的文献主体，并为这一R01应用程序的设计提供了信息。在这个R01中，我们将继续执行R21中描述的计划，将CHASE队列研究扩大到包括农村和儿科人口。我们将再招募300名参与者(城市儿童、农村儿童和农村成年人各100名)，并对他们进行至少24个月的跟踪调查，以确定癫痫复发和/或死亡的发生率。确定不良结局风险因素的研究评估将包括常规脑脊液(CSF)评估、基线神经精神筛查、CSFHIV病毒载量以及机会性感染的CSFPCR分析。城市参与者将接受大脑核磁共振和脑电图检查，所有儿童都将接受季度神经发育评估。此外，还将完成一项对癫痫和艾滋病毒患者使用抗逆转录病毒药物和EI-AEDs的暴露对照研究，以评估这种常见药物组合是否会导致抗抗抗逆转录病毒艾滋病毒。自2000年以来，一个专门的癫痫护理小组一直在奇坎卡塔医院提供服务，该医院将作为农村联盟的总部和暴露控制研究的研究地点。能力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神经心理学家)、三名赞比亚核磁共振技术专家的专业发展，以及Chase赠款管理人员。此外，将在美国、赞比亚和马拉维通过临床轮换建立放射学研究生住院医师培训课程，其中突出的神经放射学部分。一名赞比亚医学院毕业生将完成放射学实习，并在今年R01期间无缝过渡到赞比亚教员职位，在当地提供专业知识。这项工作将对撒哈拉以南非洲一个大型国家艾滋病毒携带者癫痫障碍的流行病学产生重要的见解，并确定联合使用抗逆转录病毒药物和IE-AEDs的临床相关后果，从而为护理经历癫痫的HIV+患者的临床医生提供必要的证据，以决定是否/何时启动AEDs。Chase R01还将告知政策制定者需要(或不需要)为需要艾滋病毒和癫痫双重治疗的人提供替代药物方案。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方面的“差距”，从而确定改善卫生服务以造福这一人群的优先事项。

 DESCRIPTION (provided by applicant): 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.