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

描述（由申请人提供）：与美国和欧洲相比，撒哈拉以南非洲的儿童艾滋病毒/艾滋病疫情继续扩大。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，但关于艾滋病毒/艾滋病对非洲儿童健康的影响的记录仍然很少。没有关于抗逆转录病毒治疗对资源贫乏环境中神经发育影响的数据。在感染过程中，HIV神经侵袭和神经发病机制在很大程度上仍然未知。神经毒性亚株可能导致hiv -脑病的发展。在中枢神经系统中独特的HIV谱系的进化已被证明在HIV相关痴呆的发展中发挥作用。没有关于HIV中枢神经系统区隔在幼儿HIV脑病中的潜在作用的数据。我们建议进行一项前瞻性纵向社区研究，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（艾滋病母亲和艾滋病孤儿）影响。我们还将对HIV感染婴儿（在开始抗逆转录病毒治疗之前）的中枢神经系统中HIV环境区隔化进行横剖面表征，以检验在中枢神经系统和外周区隔中存在独特HIV环境谱系的假设，并为幼儿HIV相关中枢神经系统疾病的发病机制提供见解。最后，我们将在抗逆转录病毒治疗后中枢神经系统表现未逆转的儿童中进行HIV环境中枢神经系统区隔的纵向表征。更好地了解艾滋病毒如何影响神经发育并导致儿童脑病，最终将有助于制定治疗策略，以预防儿童和成人同样经历的神经系统并发症。

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.