VIRAL SEQUENCES IN PEDIATRIC HIV INFECTION IN PR

PR 儿童 HIV 感染的病毒序列

• 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
• 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

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 儿童艾滋病毒感染是一种健康差距。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，这种传播方式在许多发展中国家和少数民族人口中仍然是一个重要的健康问题，他们获得高质量的医疗保健的机会有限。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，有些人进展迅速（四年内），而其他人则保持控制感染，八年以上不发展艾滋病。许多因素可以解释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序列的缺陷与几例长期无进展病例有关。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速度相比导致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成分。我们有四个靶序列：达特外显子1，达特外显子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/AIDS;第2组= HIV/无AIDS）。在本初步研究中，将对每例受试者的相同序列进行纵向比较（每隔6个月进行30个月）。我们的假设是病毒基因表达水平（由LTR和达特决定）和Nef和达特的病毒序列将构成HIV感染中疾病进展率的重要决定因素。这一试点提案的具体目标的成功完成将解决我们的中期目标，即生成用于出版的数据，并用于设计一项涉及更多波多黎各儿童人群的研究，以更牢固地确定这些病毒成分在疾病进展中的作用。这项工作将解决我们的长期目标，即促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，它可能导致开发替代目前抗逆转录病毒药物的治疗方法。这一点特别重要，因为对抗逆转录病毒药物的耐药性正在形成，而且发展中国家缺乏对这些昂贵干预措施的实际设施和经济支持。