Urgent Versus Post-Stabilization ART in HIV+ Children with Severe Co-infection

严重合并感染 HIV 儿童的紧急 ART 与稳定后 ART

基本信息

批准号：
8543994
负责人：
Grace John-Stewart
金额：
$ 18.63万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-21 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8543994
关键词：
8 year old Acute Address Adult Adverse drug effect Adverse effects Affect Africa African Age Anti-Retroviral Agents Child Childhood Chronic Clinical Trials Design Cryptococcal Meningitis Cytomegalovirus Data Diagnosis Drug toxicity Early Diagnosis Early treatment Emergency Situation Epidemic Epidemiology Etiology HIV HIV-1 Height Home environment Hospitalization Hospitalized Child Hospitals Hour Immune Immune response Immunologics Immunosuppression Incidence Infant Infection Inflammatory Measures Medical Meningitis Modeling Molecular National Institute of Child Health and Human Development Newly Diagnosed Pathogenesis Prophylactic treatment Public Health RNA Randomized Randomized Clinical Trials Recovery Resources Risk Staging Syndrome Testing Time Viral Viral Load result Weight antiretroviral therapy arm base cofactor cohort experience immune activation improved interest mortality outcome forecast pathogen prevent primary outcome programs public health relevance reconstitution tuberculosis treatment uptake

项目摘要

DESCRIPTION (provided by applicant): In the regions most affected by the HIV-1 epidemic, the majority of children with HIV-1 remain undiagnosed until they experience an acute co-infection. For these children, the best time to initiate ART is not known. Urgent ART may be associated with increased side-effects, difficulty in administration and increased immune reconstitution inflammatory syndrome (IRIS), but these risks may be outweighed by prompt decrease in viral replication, faster immune recovery and better control of both HIV-1 and the concomitant infection. We propose to conduct a randomized clinical trial to determine the potential benefit of highly accelerated ART in children who are diagnosed with HIV-1 at the time of hospitalization. Hospitalized children newly diagnosed with HIV-1 infection will be randomized to receive either emergent ART (within 48 hours) or post-stabilization ART (within 2 weeks). Survival will be the primary outcome of interest and we will nest immunologic studies to define predictors of survival and IRIS. This trial will address questions of critical importance to children with HIV-1 and will result in a strong epidemiologic framework for molecular studies on pediatric HIV-1 pathogenesis and IRIS. Concurrent with the trial we will explore measures to prevent late pediatric HIV-1 diagnosis by developing models for home-based diagnosis of asymptomatic HIV-1 infected children and to provide a comparison cohort of HIV-1 infected children without severe infection. PUBLIC HEALTH RELEVANCE: In resource-poor settings, many children are first diagnosed with HIV-1 infection while hospitalized for a severe infection. Mortality is very high in these children, and it is possible that rapid initiation of antiretroviral therapy may improve prognosis. However, the potential benefits of early antiretroviral initiation must be weighed against the potential risks of increased drug toxicity or immune reconstitution inflammatory syndrome (IRIS). This study will utilize a randomized clinical trial design to compare rates of mortality and IRIS among hospitalized children newly diagnosed with HIV, who will be randomized to initiation of antiretroviral therapy during acute illness versus after stabilization of acute illness.

描述（由申请人提供）：在受HIV-1流行影响最大的地区，大多数HIV-1儿童一直无法诊断，直到他们经历了急性共同感染。对于这些孩子来说，发起艺术的最佳时机是不清楚的。紧急ART可能与副作用增加，给药难度和免疫重建炎症综合征（IRIS）有关，但是这些风险可能会因病毒复制的迅速降低，更快的免疫恢复以及对HIV-1和一致性感染的迅速减少而超过这些风险。我们建议进行一项随机临床试验，以确定在住院时被诊断出患有HIV-1的儿童高加速艺术的潜在益处。新近诊断为HIV-1感染的住院儿童将被随机分配以接受新兴艺术（在48小时内）或稳定后的艺术（在2周内）。生存将是感兴趣的主要结果，我们将嵌套免疫学研究以定义生存和虹膜的预测指标。该试验将解决对HIV-1儿童至关重要的问题，并将为小儿HIV-1发病机理和虹膜的分子研究带来强大的流行病学框架。同时，我们将通过开发用于基于家庭的无症状HIV-1感染儿童的模型，并提供对HIV-1感染没有严重感染的HIV-1感染儿童的比较，以探讨以防止小儿HIV-1诊断的措施。公共卫生相关性：在资源贫乏的环境中，许多儿童首先因严重感染而住院时被诊断出患有HIV-1感染。这些儿童的死亡率很高，抗逆转录病毒疗法的快速启动可能会改善预后。但是，必须权衡早期抗逆转录病毒启动的潜在益处与药物毒性增加或免疫重建炎症综合征（IRIS）的潜在风险。这项研究将利用随机的临床试验设计来比较新诊断为HIV的住院儿童的死亡率和虹膜，他们将在急性疾病期间与抗逆转录病毒疗法进行随机启动，而急性疾病稳定后。