Impact of HIV, immune activation, and ART on child neurodevelopment in Kenya

HIV、免疫激活和 ART 对肯尼亚儿童神经发育的影响

基本信息

批准号：
8514745
负责人：
SARAH F. BENKI-NUGENT
金额：
$ 16.98万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514745
关键词：
Address Adult Africa African Area Attention Biological Preservation Blood - brain barrier anatomy Brain CD14 gene Caring Cells Child Childhood Cognition Cognitive Collaborations Communicable Diseases Complement Complex Data Developed Countries Development Development Plans Diagnosis Disease Disease Progression Doctor of Philosophy Epidemiology Europe Foundations Growth Guidelines HIV HIV Encephalopathy HIV diagnosis High Prevalence Home environment Hypersensitivity Immune Immune response Immunologics Immunosuppression Impairment Incidence Intervention Kenya Language Learning Learning Disabilities Measures Medicine Mentors Microglia Minnesota Neurocognition Neurocognitive Neurocognitive Deficit Neurology Neuropathogenesis Neuropsychology Newly Diagnosed Nutritional Outcome Pathogenesis Performance Plasma Prevalence Prevention RNA Regimen Relative (related person)Research Research Personnel Residencies Residual state Role School-Age Population Series Severities Short-Term Memory Symptoms Time Training Translational Research Universities Viral Viral Load result Washington Work advanced disease antiretroviral therapy base career career development cofactor cognitive change cohort executive function immune activation improved infancy information processing macrophage memory process monocyte neurodevelopment novel pediatric human immunodeficiency virus processing speed programs reconstitution research and development social therapy design viral detection

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5 year career development and research plan to train the Candidate as an independent epidemiologic researcher with a focus on HIV neuropathogenesis and neurocognitive outcomes in HIV-infected children. The Candidate will answer key questions addressing the benefit of antiretroviral therapy (ART) on preservation and salvage of neurocognitive development, and the role of systemic monocyte activation as a potential mechanism of HIV-induced neurocognitive impairment. The training plan builds on the Candidate's research expertise in HIV pathogenesis, pediatric HIV and epidemiology, and will improve her understanding of HIV neuropathogenesis and its relation to cognitive development in children. The proposal provides a foundation with which the Candidate will develop an independent research program in pediatric HIV, with an emphasis on neuropathogenesis and neuroepidemiology. The mentoring plan integrates a highly productive collaboration between pediatric HIV researchers from the Kenya Research Program with institutional excellence in neurology and neuropsychology at the University of Washington. Additional expertise in neurocognitive assessments in Africa from the University of Minnesota will complement this mentoring plan. Research Plan - HIV compromises neurocognitive development in children and some neurocognitive deficits may persist despite ART. In particular, sustained immune activation, in spite of successful virological and immune response to treatment, may limit the benefit of ART. We will utilize existing and novel pediatric HIV cohorts to undertake new neurocognitive studies. In Aim 1, we will determine the extent to which early ART started in infancy preserves long-term neurocognition and will identify prevalence, types and cofactors of neurocognitive deficits. In Aim 2, we will determine prevalence and correlates of neurocognitive deficits in children diagnosed later in childhood who initiate ART and are followed thereafter. In Aim 3, we will determine the relative influence of viral, immunologic and immune activation on neurocognitive outcomes in each group of HIV-infected and treated children. We hypothesize that early- and late-ART can salvage neurocognitive outcomes and that longer duration of systemic monocyte activation will correlate with severity of neurocognitive deficits. We anticipate that data from these studies will inform interventions to optimize neurocognitive outcomes in children with HIV. This training opportunity will result in the Candidate developing an independent translational research program focused on mechanisms and prevention of neurocognitive impairment in HIV-infected children.

描述（由申请人提供）：该提案描述了一个为期 5 年的职业发展和研究计划，旨在将候选人培训为独立的流行病学研究员，重点研究 HIV 感染儿童的 HIV 神经发病机制和神经认知结果。候选人将回答一些关键问题，涉及抗逆转录病毒治疗 (ART) 对神经认知发育的保存和挽救的益处，以及全身单核细胞激活作为 HIV 引起的神经认知损伤的潜在机制的作用。该培训计划以候选人在艾滋病毒发病机制、儿科艾滋病毒和流行病学方面的研究专业知识为基础，并将提高她对艾滋病毒神经发病机制及其与儿童认知发展的关系的理解。该提案为候选人开发儿科艾滋病毒独立研究项目奠定了基础，重点是神经发病机制和神经流行病学。该指导计划整合了肯尼亚研究计划的儿科艾滋病毒研究人员与华盛顿大学神经病学和神经心理学领域的卓越机构之间的高效合作。明尼苏达大学在非洲神经认知评估方面的其他专业知识将补充这一指导计划。研究计划——艾滋病毒会损害儿童的神经认知发育，尽管接受了抗逆转录病毒治疗，一些神经认知缺陷可能仍然存在。特别是，尽管对治疗产生了成功的病毒学和免疫反应，但持续的免疫激活可能会限制 ART 的益处。我们将利用现有的和新的儿科艾滋病毒队列进行新的神经认知研究。在目标 1 中，我们将确定从婴儿期开始的早期 ART 在多大程度上保留长期神经认知，并将确定神经认知缺陷的患病率、类型和辅助因素。在目标 2 中，我们将确定在儿童期后期诊断并开始 ART 并随后进行随访的儿童中神经认知缺陷的患病率和相关性。在目标 3 中，我们将确定病毒、免疫和免疫激活对每组 HIV 感染和治疗儿童的神经认知结果的相对影响。我们假设早期和晚期 ART 可以挽救神经认知结果，并且全身单核细胞激活的持续时间较长将与神经认知缺陷的严重程度相关。我们预计这些研究的数据将为优化艾滋病毒儿童神经认知结果的干预措施提供信息。此次培训机会将导致候选人正在开发一个独立的转化研究项目，重点关注艾滋病毒感染儿童神经认知障碍的机制和预防。