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：
7848155
负责人：
Annelies T.A. Van Rie
金额：
$ 41.44万
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 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7848155
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 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 Intervention Time Training Translating Universities Viral Viral Load result Virus Work antiretroviral therapy base brain tissue calcification cerebral atrophy combat env Genes epidemiology study evidence base experience fetal drug exposure genetic variant insight meetings mortality neurobehavioral neurobehavioral disorder neurodevelopment neurotropic virus pediatric AIDS pediatric human immunodeficiency virus prevent prospective social statistics teacher 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。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

"They have already thrown away their chicken": barriers affecting participation by HIV-infected women in care and treatment programs for their infants in Blantyre, Malawi.

DOI：
10.1080/09540121.2012.656570
发表时间：
2012
期刊：
AIDS care
影响因子：
1.7
作者：
Donahue MC;Dube Q;Dow A;Umar E;Van Rie A
通讯作者：
Van Rie A

Performance of HIV Rapid Tests Among Breastfeeding, Malawian Infants.

马拉维婴儿母乳喂养中艾滋病毒快速检测的表现。

DOI：
10.1097/inf.0000000000001384
发表时间：
2017
期刊：
The Pediatric infectious disease journal
影响因子：
0
作者：
Smith,EmilyR;Sheahan,AnnaD;Heyderman,RobertS;Miller,WilliamC;Wheeler,Stephanie;Hudgens,Michael;Nelson,JulieAE;Dube,Queen;VanRie,Annelies
通讯作者：
VanRie,Annelies

The effect of HIV infection and exposure on cognitive development in the first two years of life in Malawi.

马拉维艾滋病毒感染和暴露对生命头两年认知发展的影响。

DOI：
10.1016/j.ejpn.2019.11.004
发表时间：
2020
期刊：
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
影响因子：
0
作者：
Struyf,Thomas;Dube,Queen;Cromwell,ElizabethA;Sheahan,AnnaD;Heyderman,RobertS;VanRie,Annelies
通讯作者：
VanRie,Annelies

Timing of HIV Seroreversion Among HIV-Exposed, Breastfed Infants in Malawi: Type of HIV Rapid Test Matters.

马拉维暴露于艾滋病毒的母乳喂养婴儿中艾滋病毒血清逆转的时间：艾滋病毒快速检测的类型很重要。

DOI：
10.1007/s10995-016-2152-4
发表时间：
2017
期刊：
Maternal and child health journal
影响因子：
2.3
作者：
Smith,EmilyR;Hudgens,Michael;Sheahan,AnnaD;Miller,WilliamC;Wheeler,Stephanie;Nelson,JulieAE;Dube,Queen;VanRie,Annelies
通讯作者：
VanRie,Annelies