Markers of Long-Term Suppression of HIV in Pre-adolescents treated from Infancy

从婴儿期开始接受治疗的青春期前儿童艾滋病毒长期抑制的标志物

基本信息

批准号：
8631035
负责人：
Deborah Persaud
金额：
$ 32.12万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-05 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8631035
关键词：
16 year old AIDS/HIV problem Achievement Acute Adolescence Adolescent Adult Age Age-Months Alleles Anti-Retroviral Agents Antibody Formation Biological Assay Biological Markers CD14 gene CD4 Positive T Lymphocytes Caring Cells Child Childhood Clinical Trials Coculture Techniques Cohort Studies DNA Dideoxy Chain Termination DNA Sequencing Early treatment Enzyme-Linked Immunosorbent Assay Granulocyte-Macrophage Colony-Stimulating Factor HIV HIV Genome HIV Infections Highly Active Antiretroviral Therapy IL8 gene Immune Immune response Immunity Immunologics Infant Infection Inflammation Inflammatory Interferons Interleukin-1 Interleukin-10 Interleukin-2 Interleukin-6 Knowledge Lead Length Long-Term Effects Long-Term Survivors Measures Modeling Outcome Pathogenesis Pharmaceutical Preparations Phylogenetic Analysis Plasma Population Prevalence Protocols documentation RNA Residual state Rest TNF gene Testing Therapeutic Time Study Vaccination Viral Viral Load result Viremia Virus Virus Replication Western Blotting Wit base cohort cytokine deep sequencing early adolescence effective therapy immune activation improved infancy insight novel pediatric human immunodeficiency virus infection public health relevance purge tool treatment duration treatment strategy virus host interaction young adult

项目摘要

DESCRIPTION (provided by applicant): In early-treated children, HAART leads to a unique state of viral persistence whereby HIV replication is controlled solely by antiretroviral drugs wit little HIV-specific immunity (elite-treatment responders). We hypothesize that long-term early effective therapy of infants may promote a state of HIV persistence that is distinct from long-term treated adults that is comprised of negligible levels of proviral DNA, a nondetectable resting CD4+T cell latent replication-competent viral reservoir, absent residual viremia, HIV specific immune responses, immune activation and inflammation. In the context of the PHACS/AMP study, we will measure the following in a cohort of preadolescent pediatric long-term elite treatment responders: 1) Determine the long- term effects of early HAART on the size of proviral and replication-competent HIV reservoirs in perinatally HIV- infected pre-adolescents and adolescents treated from infancy, 2) Examine the long-term effects of early HAART from infancy on the dynamics of HIV persistence and immune outcomes in perinatally HIV-infected pre-adolescents and adolescents, and 3) Determine the long-term effect of early HAART on diversity of proviral and replication-competent HIV reservoirs in pre-adolescents and adolescents treated from infancy. The proposed project will improve scientific knowledge on the long-term virologic and immunologic effects of early HAART for infants who are now likely to survive to young adulthood and provide a critical framework for defining HIV CURE in clinical trials aimed at achieving HIV CURE for children and adolescents.

描述（由申请人提供）：在经过早期治疗的儿童中，HAART导致了独特的病毒持久状态，从而仅由抗逆转录病毒药物控制了艾滋病毒特异性免疫力（Elite-Chartment-治疗响应者）。我们假设婴儿的长期早期有效治疗可能会促进HIV持久性状态，该状态与长期治疗的成年人不同，该状态由可忽略不计的前病毒DNA，一种可忽视的静息CD4+T细胞潜在复制性复制性病毒性储存剂，不含残留病毒性免疫免疫反应和发炎。在PHAC/AMP研究的背景下，我们将在一系列前小儿长期的精英治疗响应群体中衡量以下内容：1）确定早期HAART对临时和复制的艾滋病毒和复制的艾滋病毒储量的长期影响，对周围感染的艾滋病毒感染者的围绕感染者的影响和早期的临时效果的动态效果，该疗程的生长率对这种效果的影响，对这种效果进行了良好的效果。 HIV感染的艾滋病毒持续性和免疫结局在受HIV感染的预种植者和青少年中，以及3）确定早期HAART对前预种植者和青少年在接受治疗的前预种植者和青少年中早期HAART对抗病毒和复制的艾滋病毒多样性的长期影响。拟议的项目将改善对早期HAART长期病毒学和免疫学影响的科学知识，这些婴儿现在可能生存到年轻人成年后生存，并为在旨在实现儿童和青少年艾滋病毒治疗的临床试验中定义HIV治疗提供了关键框架。