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

描述(申请人提供)：与美国和欧洲形成鲜明对比的是，撒哈拉以南非洲的儿科艾滋病毒/艾滋病疫情继续扩大。围产期艾滋病毒感染对大脑发育、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没有得到充分的记录。在资源匮乏的环境下，没有关于抗逆转录病毒治疗对神经发育的影响的数据。HIV神经侵袭的机制和感染过程中的神经发病机制在很大程度上仍不清楚。神经毒力亚株可能与HIV脑病的发生有关。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了作用。目前尚无关于艾滋病毒中枢神经系统区划在幼儿艾滋病毒脑病中的潜在作用的数据。我们建议进行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第一级(艾滋病毒暴露和感染)和第二级(产妇艾滋病和艾滋病孤儿)影响。我们还将对感染HIV的婴儿进行CNS内HIV环境区划的横断面表征(在开始抗逆转录病毒治疗之前)，以测试CNS中存在独特的HIV环境谱系与外周间隔的假设，并为幼儿HIV相关CNS疾病的发病机制提供洞察力。最后，我们将根据ART对其中枢神经系统表现不逆转的儿童的HIV env CNS分区进行纵向表征。更好地了解艾滋病毒如何影响儿童的神经发育和引起脑病，最终将有助于制定治疗战略，以预防儿童和成年人都经历的神经并发症。

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.