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R21资助的HIV相关癫痫发作和癫痫队列（CHASE）研究，招募了95名患有HIV和新发癫痫发作的城市成年人，描述了癫痫发作病因，并提供了对该人群癫痫发生率和风险因素的初步了解。CHASE还研究了使用队列研究设计的可行性，以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。CHASE R21研究结果对有关该人群的有限文献做出了显着贡献，并为该R 01应用程序的设计提供了信息。在本R 01中，我们将继续实施R21中描述的计划，将CHASE队列研究扩展至包括农村和儿科人群。我们将另外招募300名参与者（城市儿童、农村儿童和农村成人各100名），并对他们进行至少24个月的随访，以确定复发性癫痫发作和/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）评价、基线神经精神筛查和CSF HIV病毒载量以及CSF PCR分析（机会性感染）。将在城市参与者中获得大脑MRI和EEG，所有儿童将接受季度神经发育评估。此外，还将完成一项针对癫痫和艾滋病毒感染者的抗逆转录病毒药物和EI-AED的安全对照研究，以评估这种常见的药物组合是否会导致抗逆转录病毒药物耐药的艾滋病毒。自2000年以来，一个专门的癫痫护理小组一直在Chikankata医院提供服务，该医院将作为农村联盟的总部和安全对照研究的研究地点。能力建设活动将包括对两名赞比亚初级学者（一名儿科医生和一名神经心理学家）、三名赞比亚磁共振成像技术人员和CHASE赠款管理人员的专业发展。此外，将通过在美国、赞比亚和马拉维的临床轮换建立放射学研究生住院医师培训课程，其中包括突出的神经放射学部分。一名赞比亚医学院毕业生将在R 01期间完成放射学实习，并无缝进入赞比亚教师职位，在当地提供专业知识。这项工作将产生重要的见解，在一个大的，撒哈拉以南非洲国家的艾滋病毒感染者之间的癫痫发作疾病的流行病学，以及确定临床相关的后果，抗逆转录病毒药物和IE-AED的共同使用，从而提供临床医生照顾艾滋病毒+个人谁经历癫痫发作所需的证据，以决定是否/何时启动AED。CHASE R 01还将告知政策制定者是否需要（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，这项工作可以确定护理质量方面的“差距”，为改善卫生服务的优先事项提供信息，以使这一人群受益。

 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.