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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 一项前瞻性队列研究，旨在估计感染艾滋病毒母亲(来源人群)所生的孩子在出生后头两个月可能与宫内暴露于抗逆转录病毒治疗和/或暴露有关的疾病和诊断的发生率。这项研究将使用登记方法在注册时对12岁的儿童进行积极监测。 将在多个领域寻找子宫和/或生命头两个月因接触ART而出现异常的情况，包括代谢、生长、心脏、神经学、神经发育、行为、语言和听力领域。 将通过评估等级检查临床和实验室数据的异常情况：将确定不良事件(AE)，选定的不良事件将触发预定义的额外评估？重大观察结果将被定义为案例，整个研究范围内的重大案例模式将被定义为信号。这些感兴趣的事件的发生将随时间和ART方案进行监测，并与可能提示信号的历史数据进行比较。一些信号可以使用现有的和/或先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的研究。 SMARTT研究将检查抗逆转录病毒药物在预防艾滋病毒传播方面的毒性，包括较新药物和组合的短期毒性，以及长期毒性和微妙不良影响等悬而未决的问题。 SMARTT的具体目标是：创建一个静态监测队列，以扩大先前在WITS、PACTG 219C、P1025和其他类似的儿科队列研究中登记的儿童的特定领域数据收集； 创建一个动态监测队列，以审查在宫内和/或出生后头两个月新接触抗逆转录病毒药物的儿童的特定领域数据； 为每个领域确定一组定义可能存在抗逆转录病毒药物毒性的“信号”的“触发因素”，并将这些信号的发生情况与以前收集的数据和通过抗逆转录病毒药物的暴露进行比较；鼓励和促进以假设为导向的研究的发展，以评估一个“信号”是否是在子宫和/或生命的头两个月中暴露于抗逆转录病毒药物的结果。 领域特定目标和特定目标一般目标 评估由感染艾滋病毒的母亲在宫内和/或出生后头两个月接触抗逆转录病毒药物的未感染艾滋病毒的儿童的生长和身体组成、代谢功能、心脏功能、神经发育功能以及语言、听力和其他功能。 代谢功能与生长发育 评估身体生长和身体成分异常信号的发生：评估器官功能测量中异常信号的出现，包括肝脏、肌肉和胰腺；以及评估其他毒素暴露(例如，宫内合法和非法药物暴露或出生后铅等其他毒素)可能是上述信号的替代解释。 心功能：确定队列儿童心功能不全的信号。 神经学、神经发育、行为、语言和听力：确定神经、神经发育、语言、社交和行为障碍的特定年龄信号：婴儿期。识别早期认知、语言和社会功能的神经和神经发育信号；蹒跚学步的孩子。识别早期认知技能、言语和语言涌现以及行为功能障碍的信号； 学前班。识别认知、语言、行为和社交能力方面的神经发育/神经损伤的信号；以及 学龄儿童。识别认知发育、语言、行为、社交和执行功能障碍的信号。 以确定其他神经系统疾病，如小头症、中风、发热性和非发热性惊厥。识别听力障碍的不良信号。 其他感兴趣的领域：确定上面未涵盖的可能是不良信号的诊断和感兴趣的情况。这些包括但不限于出生缺陷、不明原因的死亡和造血系统的异常。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. 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. 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.