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：
7624321
负责人：
Annelies T.A. Van Rie
金额：
$ 41.03万
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/7624321
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 Autopsy Base Sequence Biological Assay Brain Caregivers Central Nervous System Diseases Cerebrospinal Fluid Child Childhood Communities Data Democratic Republic of the Congo Deterioration Development Drug usage Early Diagnosis Effectiveness Encephalopathies Epidemic Epidemiology Europe Evolution Growth HIV HIV Antibodies HIV Encephalopathy HIV Infections HIV-1 Health Illicit Drugs Incidence Infant Infection Intervention Invaded Laboratories Language Development Life Maintenance Medical Neurologic Neuropathogenesis Opportunistic Infections Orphan Pathogenesis Patients Pattern Perinatal Peripheral Phase Plasma Play Population Genetics Property Psychotic Disorders Public Health Rehabilitation therapy Research Research Personnel Resources Role Science Testing Therapeutic Intervention Time Training Universities Viral Viral Load result Virus antiretroviral therapy base brain tissue combat depression env Genes epidemiology study experience genetic variant insight neurobehavioral neurodevelopment neurotropic virus pediatric human immunodeficiency virus prevent prospective statistics therapeutic development 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）：与美国和欧洲相比，撒哈拉以南非洲地区的儿童艾滋病毒/艾滋病疫情持续扩大。围产期艾滋病毒感染对大脑发育以及发育里程碑的实现和维持具有重大影响。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鲜有记录。没有关于资源匮乏地区抗逆转录病毒治疗对神经发育影响的数据。 HIV 神经侵袭和感染过程中神经发病机制的机制在很大程度上仍不清楚。神经毒力亚株可能是艾滋病毒脑病发生的原因。中枢神经系统中独特的艾滋病毒谱系的进化已被证明在艾滋病毒相关痴呆的发展中发挥着作用。目前还没有关于 HIV 中枢神经系统区室化在幼儿 HIV 脑病中的潜在作用的数据。我们建议开展一项基于社区的前瞻性纵向研究，以确定艾滋病毒流行对刚果民主共和国幼儿神经发育的一级（艾滋病毒暴露和感染）和二级（艾滋病孕产妇和艾滋病孤儿）影响。我们还将对感染 HIV 的婴儿（在开始 ART 之前）中枢神经系统中的 HIV 包膜区室化进行横断面表征，以检验中枢神经系统与外周区室中存在独特的 HIV 包膜谱系的假设，并深入了解中枢神经系统中的 HIV 包膜谱系。幼儿中艾滋病毒相关中枢神经系统疾病的发病机制。最后，我们将对那些中枢神经系统表现在 ART 后未逆转的儿童中的 HIV 环境中枢神经系统区划进行纵向表征。更好地了解艾滋病毒如何影响儿童神经发育并导致儿童脑病最终将有助于制定治疗策略，以预防儿童和成人所经历的神经系统并发症。