Host epigenetic and mitochondrial function in HIV-infected children

HIV感染儿童的宿主表观遗传和线粒体功能

• 批准号: 8703154
• 负责人: Louise Kuhn
• 金额: $ 71.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703154
• 关键词: 2 year old; 9 year old; Acute; Adherence; Adult; Africa South of the Sahara; Aftercare; Age; Aging; Anti-Retroviral Agents; Automobile Driving; Biological Models; Blood specimen; Caring; Cellular Stress; Child; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Comorbidity; DNA Methylation; Data; Databases; Development; Developmental Process; Disease; Disease Progression; Dyslipidemias; Enrollment; Ensure; Enzymes; Epidemiologic Studies; Epidemiology; Epigenetic Process; Etiology; Event; Fatty acid glycerol esters; Frequencies; Functional disorder; Future; Genes; Grant; HIV; HIV Infections; Health; Household; Immune; Infection; Inflammation; Intervention; Investigation; Laboratories; Life; Lipodystrophy; Long-Term Effects; Maintenance; Malignant Neoplasms; Measures; Metabolic; Methodology; Methods; Mitochondria; Mitochondrial DNA; Natural History; Neurologic; Outcome; Participant; Pathogenesis; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Population; Protocols documentation; Recruitment Activity; Regimen; Research; Resources; Role; Sampling; School-Age Population; Siblings; Site; South Africa; Specimen; Technology; Test Result; Testing; Time; Tissues; Toxic effect; age related; antiretroviral therapy; base; cohort; follow-up; improved; infancy; interest; mitochondrial dysfunction; novel; prospective; pyrosequencing; repository; senescence; treatment site

DESCRIPTION (provided by applicant): Perinatally HIV-infected children provide a unique model system to study the chronic effects of growing up with HIV. We propose to re-enroll 500 HIV-infected children age 5-9 years at two treatment sites in Johannesburg, South Africa. These children are prior participants in clinical studies who initiated therapy during the first two year of life and have detailed clinical information, HIV-related laboratory results and over 10,000 blood specimens stored in repositories. We will prospectively follow the re-enrolled children and collect standardized clinical data on co-morbidities, toxicities and complications, laboratory data on HIV-related parameters and blood samples and other specimens for special studies. We will also enroll a cross-sectional sample of 250 uninfected children (household/sibling controls) frequency-matched by age within 3-month intervals to the re- enrolled children at the time of recruitment. We will integrate the newly-collected, follow-up data and samples with the historical databases and repositories to provide a platform to investigate (1) host epigenetics and (2) mitochondrial function and their relations with HIV disease progression, drug regimens, and metabolic complications in HIV-infected children. First, using well-established array-based methods and pyrosequencing, we propose to identify the spectrum of gene-specific DNA methylation changes that accompany perinatally- acquired HIV infection and HIV treatment. Second, utilizing both stored and newly-collected specimens, we propose to test whether mitochondrial dysfunction (as measured by novel methods of enzyme function and cell stress) exacerbates chronic inflammation and immune senescence underlying HIV disease progression and the metabolic complications that may accompany long-term treatment. Our prospective cohort, building on an extensive and well-characterized perinatally-infected population, will provide a valuable resource to undertake these and future pathogenesis-oriented studies to inform development of complementary interventions to improve long-term outcomes of HIV-infected children in sub-Saharan Africa.

描述（由申请人提供）：围产期感染艾滋病毒的儿童提供了一个独特的模型系统来研究艾滋病毒成长的慢性影响。我们建议在南非约翰内斯堡的两个治疗点重新招收500名5-9岁感染艾滋病毒的儿童。这些儿童是临床研究的先前参与者，在出生后的头两年开始治疗，并拥有详细的临床信息、与艾滋病毒相关的实验室结果和储存在储存库中的10,000多个血液标本。我们将对重新入组的儿童进行前瞻性随访，并收集有关合并症、毒性和并发症以及实验室数据的标准化临床数据