Neurodevelopment and Imaging among HIV-infected Children from the PREDICT study

PREDICT 研究中艾滋病毒感染儿童的神经发育和影像学

基本信息

批准号：
8243680
负责人：
VICTOR VALCOUR
金额：
$ 61.87万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-18 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8243680
关键词：
AIDS/HIV problem Accounting Address Adult Age Age-Months Anisotropy Anti-Retroviral Agents Body measure procedure Brain Brain Injuries Brain imaging Cambodia Child Child Behavior Checklist Childhood Injury Cognitive Control Groups Corpus Callosum Data Diffusion Magnetic Resonance Imaging Disease Early treatment Enrollment Ensure Evaluation Funding Growth Guidelines HIV Hospitalization Image Immune Immunosuppression Infant International Life Longitudinal Studies Measures Microcephaly Multimodal Imaging National Institute of Allergy and Infectious Disease Neurologic Neurological outcome Neuropsychological Tests Outcome Principal Investigator Randomized Recommendation Research Design Resources Societies Speed Thailand Time Toxic effect Treatment outcome United States National Institutes of Health Work antiretroviral therapy arm base brain size brain volume comparative corpus callosum body design frontal lobe member morphometry neurodevelopment neuropsychological primary outcome processing speed programs public health relevance success treatment program trend white matter

项目摘要

DESCRIPTION (provided by applicant): There are 2.5 million children living the HIV/AIDS worldwide. Most live in resource- limited settings. Treatment guidelines for children are often based on findings in adults and seldom assembled from studies employing a randomized design. This rationale led the NIH to initiate the PREDICT study underway in Thailand and Cambodia. PREDICT uses a randomized design to determine the optimal timing of antiretroviral initiation in children. International guidelines for ART initiation in children older than 12 months continue to recommend deferring therapy until symptomatic disease or immune compromise occurs, despite studies in younger infants (CHER trial) identifying a benefit for early treatment. Treatment outcomes for older children are needed and neurodevelopmental outcomes could critically inform guidelines. This proposal will add robust neurodevelopmental and imaging outcomes to PREDICT. This work will extend our current limited evaluation of neurodevelopmental outcomes to determine if differences in long-term neuropsychological and neurological outcomes exist in relation to deferring antiretroviral therapy. We will also enroll needed HIV-negative comparative groups of HIV-exposed and unexposed children. Since microencephaly is a common manifestation of HIV in children, volumetric analyses may be most informative. Should the primary findings from PREDICT fail to identify differences by randomized group (immediate compared to deferred therapy), findings from the proposed work may have an enormous impact by informing treatment guidelines worldwide. PUBLIC HEALTH RELEVANCE: HIV treatment guidelines for children are based on incomplete evidence. Neurodevelopmental outcomes may critically inform these guidelines. The proposed work will determine the brain impact of deferring antiretroviral therapy until there is immunosuppression, as currently recommended by WHO guidelines. Our findings may have an enormous impact on worldwide treatment recommendations.

描述（由申请人提供）：全世界有250万儿童居住在艾滋病毒/艾滋病中。大多数生活在资源有限的设置中。儿童的治疗指南通常是基于成年人的发现，很少是通过采用随机设计的研究组装而来的。这种理由导致NIH启动了泰国和柬埔寨的预测研究。预测使用随机设计来确定儿童抗逆转录病毒启动的最佳时机。 12个月以上儿童的国际艺术启动指南继续建议推迟治疗，直到有症状性疾病或免疫妥协，尽管对年轻婴儿进行了研究（CHER试验）确定了早期治疗的益处。需要针对年龄较大的儿童的治疗结果，神经发育结果可能会批判性地指导指南。该建议将增加可靠的神经发育和成像结果。这项工作将扩大我们当前对神经发育结果的有限评估，以确定与推迟抗逆转录病毒疗法有关的长期神经心理学和神经学结果的差异。我们还将招募艾滋病毒暴露和未暴露儿童的HIV阴性比较组。由于微脑是儿童艾滋病毒的普遍表现，因此体积分析可能是最有用的。如果预测的主要发现无法确定随机组的差异（与递延疗法相比立即进行），则提议的工作的发现可能会通过在全球范围内告知治疗指南，从而产生巨大影响。公共卫生相关性：儿童艾滋病毒治疗指南是基于不完整的证据。神经发育结果可能会严重告知这些准则。拟议的工作将确定延迟抗逆转录病毒疗法的大脑影响，直到进行免疫抑制为止，如WHO指南目前所建议。我们的发现可能会对全球治疗建议产生巨大影响。