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

• 批准号: 8410048
• 负责人: SARAH F. BENKI-NUGENT
• 金额: $ 17.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 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/8410048
• 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

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. PUBLIC HEALTH RELEVANCE: Sarah Benki-Nugent, MS, PhD is a Senior Fellow in the Division of Allergy and Infectious Diseases, Department of Medicine at the University of Washington. The proposed career development plan and research will provide the Candidate with mentored learning in HIV neuropathogenesis and neuropsychology while conducting research to determine the extent to which antiretroviral therapy can salvage neurocognitive abilities and to identify modifiable cofactors for residual neurocognitive deficits in African HIV-infected children. Findings from this research will form the basis of the Candidate's independent career focused on improvement of neurocognitive outcomes in HIV-infected African children.

描述（由申请人提供）：该提案描述了一项为期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，重点是HIV神经病生成和HIV感染儿童的神经认知结果。候选人将回答有关抗逆转录病毒疗法（ART）对神经认知发展的保存和挽救的好处的关键问题，以及全身单核细胞激活作为HIV诱导的神经认知障碍的潜在机制的作用。该培训计划基于候选人在HIV发病机理，小儿艾滋病毒和流行病学方面的研究专业知识，并将提高她对HIV神经病发生及其与儿童认知发展的关系的理解。该提案为候选人提供了一个基础，候选人将在小儿艾滋病毒中制定独立的研究计划，重点是神经病发生和神经epidemiology。该指导计划整合了肯尼亚研究计划的小儿艾滋病毒研究人员与华盛顿大学神经病学和神经心理学方面的卓越基础之间的高效合作。明尼苏达大学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 - 艾滋病毒损害儿童的神经认知发展，尽管有艺术，但某些神经认知缺陷仍可能存在。尤其是，尽管有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的好处。我们将利用现有和新颖的儿科艾滋病毒队列进行新的神经认知研究。在AIM 1中，我们将确定婴儿期早期艺术在多大程度上保存长期神经认知，并确定神经认知缺陷的流行率，类型和辅助因子。在AIM 2中，我们将确定童年后期诊断出的儿童的神经认知缺陷的患病率和相关性，此后遵循。在AIM 3中，我们将确定病毒，免疫学和免疫激活对每组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可以挽救神经认知结果，并且更长的全身单核细胞激活持续时间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干预措施提供信息，以优化艾滋病毒儿童的神经认知结果。这个训练机会将导致 候选人制定了一项独立的转化研究计划，该计划的重点是预防感染HIV感染儿童的神经认知障碍。 公共卫生相关性：Sarah Benki-Nugent，MS，PhD是华盛顿大学医学系过敏和传染病的高级研究员。拟议的职业发展计划和研究将为候选人提供艾滋病毒神经病发生和神经心理学中的指导学习，同时进行研究以确定抗逆转录病毒疗法可以挽救神经认知能力的程度，并确定可修改的辅助因子，以确定非洲HIV HIV感染的儿童的残留神经认知缺陷。这项研究的结果将构成候选人独立职业的基础，重点是改善受HIV感染的非洲儿童的神经认知结果。