VIRAL SEQUENCES IN PEDIATRIC HIV INFECTION IN PR

PR 儿童 HIV 感染的病毒序列

基本信息

批准号：
7959132
负责人：
Richard J. Noel
金额：
$ 14.49万
依托单位：
PONCE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-09 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7959132
关键词：
AIDS/HIV problem Accounting Acquired Immunodeficiency Syndrome Address Adult Anti-Retroviral Agents Child Childhood Clinical Computer Retrieval of Information on Scientific Projects Database Data Developed Countries Developing Countries Development Disease Disease Progression Economics Elements Exons Funding Gene Expression Genetic Variation Goals Grant HIV Infections Health Infection Infection Control Institution Intervention Light Link Minority Participant Patients Pharmaceutical Preparations Pilot Projects Population Prognostic Factor Publications Puerto Rican Relative (related person)Research Research Personnel Resistance Resources Risk Role Source United States National Institutes of Health Vertical Disease Transmission Viral Viral Genes Virus Work design health care quality health disparity innovation medical schools pediatric human immunodeficiency virus infection postnatal prenatal programs therapeutic development transmission process

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pediatric HIV infection represents a health disparity. Prenatal and postnatal treatment have been remarkably effective in lowering the risk of vertical transmission in developed countries. Yet this mode of transmission remains an important health issue in many developing countries and among minority populations with limited access to high quality health care. The relative lack of studies of HIV/AIDS in children exacerbates this problem. Among vertically infected children, some progress rapidly (within four years) to AIDS, while others maintain control of the infection and do not develop AIDS for more than eight years. Many factors may account for this different clinical presentation, including genetic variation in the virus. In adult infection, deficiencies in viral nef and LTR sequences have been linked to several cases of long-term nonprogression. We will use an innovative and complementary approach of studying the viral sequences that account for rapid infection as compared to the normal or slower rate, to identify the viral elements responsible for development of AIDS in pediatric patients. We have four target sequences: tat exon 1, tat exon 2, nef, and LTR. These sequences will be compared in two groups of Puerto Rican HIV-1-infected children (Group 1 = HIV/AIDS; Group 2 = HIV/no AIDS). The same sequences will be compared longitudinally (for thirty months at six-month intervals) in each participant in this pilot study. Our hypothesis is that viral gene expression levels (determined by LTR and Tat) and viral sequences of Nef and Tat will comprise important determinants of disease progression rate in HIV infection. This successful completion of the specific aims of this pilot proposal will address our medium-term goal to generate data for publication and for use in design of a study involving a larger population of Puerto Rican children to more firmly establish the roles of these viral components in disease progression. This work will address our long-range goal of advancing our understanding of the mechanisms employed by the virus to propagate infection and cause disease. It is expected that such information will prove of clinical benefit as a prognostic factor in pediatric HIV infection. Further, it may result in the development of therapeutic alternatives to the current antiretroviral drugs. This is particularly important as resistance to antiretrovirals develops and in light of the lack of physical facilities and economic support for these expensive interventions in the developing world.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。儿童艾滋病毒感染代表了健康差异。在发达国家，产前和产后治疗在降低垂直传播风险方面非常有效。然而，这种传播方式仍然是许多发展中国家和获得高质量医疗保健机会有限的少数群体中的一个重要健康问题。对儿童艾滋病毒/艾滋病的研究相对缺乏，加剧了这一问题。在垂直感染的儿童中，有些儿童迅速（四年内）发展为艾滋病，而其他儿童则保持对感染的控制，并且在八年以上没有发展为艾滋病。许多因素可能导致这种不同的临床表现，包括病毒的遗传变异。在成人感染中，病毒 nef 和 LTR 序列的缺陷与一些长期不进展的病例有关。我们将使用一种创新和互补的方法来研究与正常或较慢的感染率相比快速感染的病毒序列，以确定导致儿科患者发生艾滋病的病毒元件。我们有四个目标序列：tat 外显子 1、tat 外显子 2、nef 和 LTR。这些序列将在两组波多黎各 HIV-1 感染儿童中进行比较（第 1 组 = HIV/艾滋病；第 2 组 = HIV/无艾滋病）。相同的序列将在该试点研究的每个参与者中进行纵向比较（三十个月，每六个月一次）。我们的假设是，病毒基因表达水平（由 LTR 和 Tat 决定）以及 Nef 和 Tat 的病毒序列将构成 HIV 感染疾病进展率的重要决定因素。该试点提案具体目标的成功完成将实现我们的中期目标，即生成用于发表的数据，并用于设计一项涉及更多波多黎各儿童的研究，以更牢固地确定这些病毒成分在疾病进展。这项工作将实现我们的长期目标，即增进我们对病毒传播感染和引起疾病的机制的理解。预计这些信息将证明作为儿科 HIV 感染的预后因素具有临床益处。此外，它可能会导致当前抗逆转录病毒药物的治疗替代品的开发。随着抗逆转录病毒药物耐药性的发展，以及发展中国家缺乏对这些昂贵干预措施的物质设施和经济支持，这一点尤为重要。