权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pediatric HIV-encephalopathy in DRC: effect of ART & role of compartmentalization

刚果民主共和国儿童艾滋病毒脑病：ART 的效果

基本信息

批准号：
7425915
负责人：
Annelies T.A. Van Rie
金额：
$ 42.14万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7425915
关键词：
AIDS Dementia Complex AIDS/HIV problem Achievement Acquired Immunodeficiency Syndrome Adult Africa Africa South of the Sahara African Age Age of Onset Anti-Retroviral Agents Area Autopsy Basal Ganglia Base Sequence Biological Assay Brain Caregivers Central Nervous System Diseases Cerebrospinal Fluid Child Childhood Communities Complication Data Democratic Republic of the Congo Deterioration Development Developmental Delay Disorders Diagnosis Disease Disease regression Drug usage Early Diagnosis Economics Education Effectiveness Encephalopathies Epidemic Epidemiology Europe Evolution Growth HIV HIV Antibodies HIV Encephalopathy HIV Infections HIV-1 Health Illicit Drugs Immunosuppression Impaired cognition Incidence Infant Infection Institution Intervention Invaded Laboratories Language Development Life Limb structure Maintenance Measures Medical Mental Depression Microcephaly Morbidity - disease rate Natural History Neuraxis Neurologic Neuropathogenesis North Carolina Opportunistic Infections Orphan Pathogenesis Patients Pattern Perinatal Peripheral Phase Plasma Play Policies Population Genetics Process Property Psychotic Disorders Public Health Qualifying Recommendation Recording of previous events Rehabilitation therapy Reporting Research Research Institute Research Personnel Resources Role Scholarship Science Seizures Spastic Students Symptoms Systemic disease Technology Testing Therapeutic Therapeutic Intervention Therapeutic immunosuppression Time Training Translating Universities Viral Viral Load result Virus Work antiretroviral therapy base brain tissue calcification cerebral atrophy env Genes epidemiology study experience fetal drug exposure genetic variant insight mortality neurobehavioral neurobehavioral disorder neurodevelopment neurotropic virus pediatric AIDS prevent prospective social statistics teacher time use virology

项目摘要

DESCRIPTION (provided by applicant): In contrast to the US and Europe, the pediatric HIV/AIDS epidemic in sub-Saharan Africa continues to expand. Perinatal HIV infection has a significant impact on brain development, and the achievement and maintenance of developmental milestones. Even though more than 80% of childhood HIV infections occur in Africa, the impact of HIV/AIDS on the health of African children remains poorly documented. No data exists on the impact of antiretroviral treatment on neurodevelopment in resource poor settings. The mechanisms of HIV neuroinvasion and neuropathogenesis over the course of infection remain largely unknown. Neurovirulent substrains may be responsible for the development of HIV-encephalopathy. The evolution of unique HIV lineages in the CNS has been shown to play a role in the development of HIV- associated dementia. No data are available on the potential role of HIV CNS compartmentalization in HIV encephalopathy in young children. We propose to conduct a prospective longitudinal community-based study to determine the first order (HIV exposure and infection) and second order (maternal AIDS and AIDS orphans) effects of the HIV epidemic on the neurodevelopment of young children in the Democratic Republic of Congo. We will also perform a cross- sectional characterization of HIV env compartmentalization in the CNS in HIV-infected infants (prior to initiating ART) to test the hypothesis that unique HIV env lineages are present in CNS versus peripheral compartments, and to provide insight into the pathogenesis of HIV-associated CNS disease in young children. Finally, we will perform a longitudinal characterization of HIV env CNS compartmentalization in children whose CNS manifestations do not reverse following ART. A better understanding of how HIV impacts neurodevelopment and causes encephalopathy in children would ultimately aid in the development of therapeutic strategies to prevent neurological complications experienced by children and adults alike.

描述（由申请人提供）：与美国和欧洲相反，撒哈拉以南非洲的儿科艾滋病毒/艾滋病流行继续扩大。围产期HIV感染对大脑发育以及发育里程碑的实现和维持有重大影响。尽管80%以上的儿童艾滋病毒感染发生在非洲，但艾滋病毒/艾滋病对非洲儿童健康的影响仍然缺乏记录。没有数据显示抗逆转录病毒治疗对资源匮乏环境中神经发育的影响。HIV在感染过程中的神经侵袭和神经发病机制在很大程度上仍然未知。神经毒力亚株可能是导致HIV脑病的原因。CNS中独特的HIV谱系的进化已被证明在HIV相关性痴呆的发展中起作用。目前尚无关于HIV CNS区室化在幼儿HIV脑病中的潜在作用的数据。我们建议进行前瞻性的纵向社区为基础的研究，以确定第一顺序（艾滋病毒暴露和感染）和第二顺序（孕产妇艾滋病和艾滋病孤儿）的影响，艾滋病毒流行的幼儿神经发育的刚果民主共和国。我们还将对HIV感染婴儿（开始ART前）CNS中HIV env区室化进行横断面表征，以检验CNS与外周区室中存在独特HIV env谱系的假设，并深入了解幼儿中HIV相关CNS疾病的发病机制。最后，我们将进行一个纵向表征艾滋病毒env中枢神经系统分区的儿童，其中枢神经系统的表现不逆转以下ART。更好地了解艾滋病毒如何影响神经发育和导致脑病的儿童将最终帮助发展的治疗策略，以防止神经系统并发症的儿童和成人一样。