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：
8467195
负责人：
Deborah Persaud
金额：
$ 28.35万
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 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8467195
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-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）：在早期治疗的儿童中，HAART 导致病毒持续存在的独特状态，其中 HIV 复制仅由抗逆转录病毒药物控制，几乎没有 HIV 特异性免疫力（精英治疗反应者）。我们假设，对婴儿进行长期早期有效治疗可能会促进 HIV 持续存在的状态，这种状态与长期接受治疗的成人不同，其由可忽略水平的前病毒 DNA 组成，这是一种不可检测的静息 CD4+T 细胞潜在复制能力病毒库。，不存在残留病毒血症、HIV特异性免疫反应、免疫激活和炎症。在 PHACS/AMP 研究的背景下，我们将在青春期前儿科长期精英治疗反应者队列中测量以下内容： 1) 确定早期 HAART 对前病毒和有复制能力的 HIV 病毒库大小的长期影响在围产期 HIV 感染的青春期前和从婴儿期开始接受治疗的青少年中，2) 检查婴儿期早期 HAART 对 HIV 持续性动态和免疫结果的长期影响围产期感染 HIV 的青春期前和青少年，以及 3) 确定早期 HAART 对从婴儿期开始接受治疗的青春期前和青少年中原病毒和复制能力 HIV 病毒库多样性的长期影响。拟议的项目将提高关于早期 HAART 对现在可能存活到成年早期的婴儿的长期病毒学和免疫学影响的科学知识，并为临床试验中定义 HIV 治愈提供关键框架，旨在实现儿童和儿童的 HIV 治愈。青少年。