Lipidome composition, immune activation and subclinical vascular disease in Adolescents with perinatally acquired HIV in Uganda

项目摘要/摘要： 全世界有210万15岁以下的儿童感染艾滋病毒；其中绝大多数 已通过围产期感染艾滋病毒(PHIV)并居住在东部和南部非洲。活着的孩子 艾滋病毒携带者现在预计可以活到青春期和成年，这样 青少年现在是最大的艾滋病毒携带者。几种合并症， 包括心脏新陈代谢，与增强免疫活性和 感染艾滋病毒的成年人尽管有病毒抑制，但仍有炎症反应。因为它的尺寸小， 由于儿科数据的缺乏，关于其机制和程度存在争议。 在这些年轻的人群中，在形成期炎症加剧是值得关注的。 脂类组学分析揭示了脂类和脂肪酸之间的联系 成分与炎症和几种疾病，包括心脏新陈代谢并发症。 该项目的总体目标是对艾滋病毒及其相关因素有新的认识。 免疫激活与亚临床心血管疾病。我们将不偏不倚地使用小说 分析整合脂体并带来识别信号的创新方法 与脂质处理相关的级联反应可能预测心血管并发症 艾滋病病毒。在一项对100名艾滋病毒感染者以及年龄和性别匹配的未感染对照的纵向研究中，这 该项目的目标是在96周内测量脂体，以确定与此相关的脂类紊乱 与艾滋病毒和与免疫激活相关的途径有关。我们将调查是否支持- 炎性血脂是亚临床血管疾病的预测指标。此外，我们还将检查 特定的ART课程以及个别抗逆转录病毒药物在脂体上的作用。 这项拟议的研究利用了Dirajlal-Fargo博士在乌干达进行的K23研究的丰富数据。 这项研究将建立在病毒抑制的PHIV青少年的良好表型队列的基础上 和年龄、性别匹配的未感染对照组，并利用保存库标本。 纵向设计将允许数据验证和复制，这是对 先前的观测组学研究。这项研究可能揭示出新的生物标记物特征 预防青少年心血管疾病的生物学、临床和预后相关性 他们即将步入成年期，并接受了长期的艺术创作。

Project Summary/Abstract: There are 2.1 million children under 15 years living with HIV worldwide; the vast majority have perinatally acquired HIV (PHIV) and reside in Eastern and Southern Africa. Children living with PHIV are now expected to live through adolescence and well into adulthood, such that adolescents now represent the largest growing population living with HIV. Several comorbidities, including cardiometabolic, have been associated with heightened immune activation and inflammation despite viral suppression in adults living with HIV. Because of the small size and paucity of pediatric data, controversy exists regarding the mechanisms and the extent to which heightened inflammation should be concerning in this young population during formative years. Lipidomics analyses have revealed associations of lipid classes and fatty acid composition with inflammation and several diseases, including cardiometabolic complications. The overall goal of this project is to obtain new insight into PHIV and the factors associated with immune activation and subclinical cardiovascular disease. We will use novel unbiased analysis of integrated lipidomic and bring an innovative approach to identify signaling cascades related to lipid processing that may predict cardiovascular complications in PHIV. In a longitudinal study of 100 PHIV and age-and sex-matched uninfected controls, this project aims to measure the lipidome over 96 weeks to identify lipid perturbations associated with HIV and pathways associated with immune activation. We will investigate whether pro- inflammatory lipids are predictive of subclinical vascular disease. Additionally, we will examine the role of specific ART classes as well as individual antiretroviral drugs on the lipidome. The proposed study leverages the rich data of Dr. Dirajlal-Fargo’s K23 study in Uganda. This study will build on the well-phenotyped cohort of virally suppressed adolescents with PHIV and age-and sex- matched uninfected comparison group and utilize repository specimens. The longitudinal design will allow for data validation and replication, a major criticism of prior observational omics studies. This study may reveal novel biomarker signatures of biological, clinical, and prognostic relevance to prevent cardiovascular disease for adolescents who are advancing into adulthood and have received long-term ART.