VIRAL SEQUENCES IN PEDIATRIC HIV INFECTION IN PR

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 儿童艾滋病毒感染代表着健康差距。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，在许多发展中国家和获得高质量保健的机会有限的少数群体中，这种传播方式仍然是一个重要的健康问题。相对缺乏对儿童艾滋病毒/艾滋病的研究加剧了这一问题。在垂直感染的儿童中，一些人(在四年内)迅速发展为艾滋病，而另一些人保持感染控制，并在八年以上不发展为艾滋病。许多因素可能解释了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序列的缺陷与几个长期无进展的病例有关。我们将采用一种创新和互补的方法，研究与正常或较慢的感染速度相比，导致快速感染的病毒序列，以确定导致儿童患者艾滋病发展的病毒成分。我们有四个靶序列：TAT外显子1、TAT外显子2、NEF和LTR。这些序列将在波多黎各感染艾滋病毒-1的两组儿童中进行比较(第一组=艾滋病毒/艾滋病；第二组=艾滋病毒/非艾滋病)。同样的序列将在这项初步研究的每个参与者中进行纵向比较(每隔6个月进行30个月的比较)。我们的假设是，病毒基因的表达水平(由LTR和TAT决定)以及病毒的Nef和Tat序列将构成HIV感染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，即生成数据以供出版和用于设计一项涉及更多波多黎各儿童的研究，以更坚定地确定这些病毒成分在疾病发展中的作用。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导致疾病的机制的理解。预计这些信息将被证明是儿童HIV感染的一个预后因素，具有临床益处。此外，这可能会导致目前抗逆转录病毒药物的治疗替代品的开发。这一点尤其重要，因为抗逆转录病毒药物产生了抗药性，而且发展中世界对这些昂贵的干预措施缺乏实物设施和经济支持。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.