PHACS PH 100 SURVEILLANCE MONITORING FOR ART TOXICITIES STUDY IN HIV-UNINFEC

PHACS PH 100 HIV-UNINFEC 中艺术毒性研究的监测

基本信息

批准号：
8356681
负责人：
William Thomas Shearer
金额：
$ 10.38万
依托单位：
BAYLOR COLLEGE OF MEDICINE
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：
2010-12-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8356681
关键词：
12 year old Adverse effects Adverse event Age Arts Behavior Behavioral Birth Body Composition Cardiac Cessation of life Child Childhood Clinical Clinical Research Cognitive Cohort Studies Congenital Abnormality Data Data Collection Development Diagnosis Enrollment Evaluation Event Exposure to Febrile Convulsions Functional disorder Funding Grant Growth HIV Hearing Illicit Drugs Impairment Incidence Laboratories Language Language Development Lead Life Linguistics Liver Measures Metabolic Microcephaly Monitor Mothers Muscle National Center for Research Resources Neurologic New Agents Organ Pancreas Pattern Perinatal Exposure Population Prevention Principal Investigator Regimen Registries Research Research Design Research Infrastructure Resources School-Age Population Schools Seizures Signal Transduction Social Behavior Social Functioning Source Speech Stroke System Time Toddler Toxic effect Toxin United States National Institutes of Health antiretroviral therapy cohort cost drug exposure in utero executive function in utero infancy interest prospective skills social transmission process

项目摘要

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. ABSTRACT Prospective cohort study designed to estimate the incidence of conditions and diagnoses potentially related to in utero exposure to antiretroviral therapy and/or exposure in the first two months of life among children born of HIV-infected mothers (source population). The study will use a registry approach to conduct active surveillance among children 12 years of age at enrollment. Occurrences of abnormalities from ART exposure in utero and/or in the first two months of life will be sought in multiple domains, including metabolic, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing domains. Clinical and laboratory data will be examined for abnormalities through a hierarchy of evaluations: adverse events (AE) will be identified, selected AEs will trigger predefined additional evaluations, significant observations will be defined as cases, a pattern of significant study-wide cases will be defined as signals. The incidence of these events of interest will be monitored over time and by ART regimen, and compared with historical data that may be suggestive of a signal. Some signals may be testable using existing and/or previously collected data, while other signals may indicate the need for additional hypothesis-driven studies outside of SMARTT. HYPOTHESIS The SMARTT study will examine the toxicity of ART in HIV transmission prevention for the short-term toxicity of newer agents and combinations as well as the unanswered questions of longer term toxicity and subtle adverse effects. SPECIFIC AIMS The specific aims of SMARTT are: To create a Static Surveillance Cohort to extend domain-specific data collection in children previously enrolled in WITS, PACTG 219C, P1025 and other similar pediatric cohort studies; To create a Dynamic Surveillance Cohort to examine domain-specific data of children newly exposed to ART in utero and/or in the first two months of life; To identify a set of "triggers" for each domain that define a "signal" of possible ART toxicity and compare the occurrence of these signals with previously collected data and by ART exposure; and To encourage and facilitate the development of hypothesis-driven studies to evaluate whether a "signal" is the result of ART exposure in utero and/or in the first two months of life. DOMAIN-SPECIFIC OBJECTIVES AND SPECIFIC AIMS General Objectives To assess growth and body composition, metabolic function, cardiac function, neurodevelopmental function as well as speech, language, hearing and other functions in HIV-uninfected children born of HIV-infected mothers with exposure to ART in utero and/or in the first two months of life. Metabolic Function and Growth To estimate the occurrence of abnormal signals of somatic growth and body composition; To estimate the occurrence of abnormal signals in measures of organ function, including the liver, muscles, and pancreas; and To evaluate other toxin exposures (e.g., licit and illicit drug exposure in utero or other toxins such as lead after birth) that may be alternative explanations for the signals described above. Cardiac Function To identify signals of cardiac dysfunction in the cohort children. Neurologic, Neurodevelopmental, Behavior, Language, and Hearing To identify age-specific signals of neurological, neurodevelopmental, linguistic, social, and behavioral dysfunction: Infancy. To identify neurological and neurodevelopmental signals in early cognitive, linguistic, and social function; Toddler. To identify signals of dysfunction in early cognitive skills, speech and language emergence, and behavioral functioning; Pre-school. To identify signals of neurodevelopmental/neurological impairments in cognitive, linguistic, behavior, and social abilities; and School age. To identify signals of dysfunction in cognitive development, and language, behavioral, social and executive function. To identify other neurologic conditions such as microcephaly, stroke, and febrile and non-febrile seizures. To identify adverse signals of hearing dysfunction. Other Domains of Interest To identify diagnoses and conditions of interest not covered above that may be adverse signals. These include but are not limited to birth defects, unexplained death, and abnormalities of the hematopoeitic system.

该子项目是利用资源的众多研究子项目之一由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持并且子项目的主要研究者可能是由其他来源提供的，包括其他 NIH 来源。子项目可能列出的总成本代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。抽象的前瞻性队列研究旨在估计与子宫内接受抗逆转录病毒治疗和/或感染艾滋病毒的母亲所生的孩子（来源人群）出生后头两个月的接触可能相关的病症和诊断的发生率。该研究将采用登记方法对 12 岁入组儿童进行主动监测。将在多个领域寻找因子宫内和/或出生后头两个月接受 ART 导致的异常情况，包括代谢、生长、心脏、神经系统、神经发育、行为、语言和听力领域。将通过分级评估检查临床和实验室数据是否存在异常：将识别不良事件 (AE)，选定的 AE 将触发预定义的附加评估，将重大观察结果定义为病例，将确定研究范围内重大病例的模式。定义为信号。将通过 ART 方案随时间监测这些感兴趣事件的发生率，并与可能暗示信号的历史数据进行比较。一些信号可能可以使用现有和/或之前收集的数据进行测试，而其他信号可能表明需要在 SMARTT 之外进行额外的假设驱动研究。假设 SMARTT 研究将检查 ART 在艾滋病毒传播预防中的毒性，包括新药物和组合的短期毒性，以及长期毒性和微妙不良反应等尚未解答的问题。具体目标 SMARTT 的具体目标是：创建静态监测队列，以扩展先前参加 WITS、PACTG 219C、P1025 和其他类似儿科队列研究的儿童的特定领域数据收集；创建一个动态监测队列，检查在子宫内和/或出生后头两个月新接触抗逆转录病毒治疗的儿童的特定领域数据；为每个域确定一组“触发因素”，定义可能的 ART 毒性“信号”，并将这些信号的出现与之前收集的数据和 ART 暴露进行比较；和鼓励和促进以假设为驱动的研究的发展，以评估“信号”是否是子宫内和/或生命前两个月接受 ART 的结果。特定领域的目标和具体目标总体目标评估感染艾滋病毒的母亲在子宫内和/或前两年接受抗逆转录病毒治疗所生的未感染艾滋病毒的儿童的生长和身体成分、代谢功能、心脏功能、神经发育功能以及言语、语言、听力和其他功能几个月的生命。代谢功能和生长估计体细胞生长和身体成分异常信号的发生；估计器官功能测量中异常信号的发生，包括肝脏、肌肉和胰腺；和评估其他毒素暴露（例如，子宫内合法和非法药物暴露或出生后其他毒素，如铅），这可能是上述信号的替代解释。心脏功能识别队列儿童中心脏功能障碍的信号。神经病学、神经发育、行为、语言和听力识别神经、神经发育、语言、社交和行为功能障碍的年龄特异性信号：婴儿期。识别早期认知、语言和社会功能中的神经和神经发育信号；学步的儿童。识别早期认知技能、言语和语言出现以及行为功能功能障碍的信号；学前班。识别认知、语言、行为和社交能力方面的神经发育/神经损伤信号；和学龄。识别认知发展、语言、行为、社交和执行功能功能障碍的信号。识别其他神经系统疾病，例如小头畸形、中风以及热性和非热性惊厥。识别听力功能障碍的不良信号。其他感兴趣的领域识别上面未涵盖的可能是不良信号的诊断和相关状况。这些包括但不限于出生缺陷、不明原因死亡和造血系统异常。