PH 201 MEMORY FUNCTIONING IN CHILDREN AND ADOLESCENTS WITH PERINATAL HIV

PH 201 围产期 HIV 感染儿童和青少年的记忆功能

• 批准号: 8356748
• 负责人: William Thomas Shearer
• 金额: $ 1.5万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/8356748
• 关键词: 9 year old; Address; Adherence; Adolescence; Adolescent; Adult; Affect; Aging; Area; Caring; Child; Childhood; Clinical; Clinical Research; Cognitive; Cognitive deficits; Cohort Studies; Communities; Competence; Consent; Controlled Study; Development; Disease; Disease Progression; Enrollment; Evaluable Disease; Evaluation; Evaluation Studies; Event; Funding; Future; Goals; Grant; HIV; HIV-1; Impairment; Infection; Intervention; Knowledge; Learning; Life; Literature; Measures; Memory; Monitor; National Center for Research Resources; Neighborhoods; Neuraxis; Occupational; Outcome; Participant; Pattern; Penetrance; Performance; Perinatal; Pharmaceutical Preparations; Population; Population Study; Principal Investigator; Process; Protocols documentation; Provider; Public Health; Regimen; Research; Research Infrastructure; Resources; Risk; Risk Behaviors; Sampling; Schools; Severity of illness; Source; Staging; Suicide attempt; Testing; Time; United States National Institutes of Health; Virus Diseases; Visit; Youth; cohort; cost; executive function; experience; functional outcomes; improved; innovation; medication compliance; neuropsychological; prospective; prospective memory; psychological distress; skills; social; standard of care; standardize measure; success

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. This study is a prospective cohort study comparing memory and executive functioning in two groups of youth, age 9 years to 19 years at study entry: one group will be youth with perinatally acquired Human Immunodeficiency Virus (HIV)-1 infection and the other group will be perinatally HIV-1 exposed but uninfected youth. All youth enrolled will be currently participating in PHACS AMP. At least 275 evaluable participants (200 HIV-1 infected participants and 75 HIV-1 exposed, uninfected participants) will be enrolled. Participants will be followed for two years and will receive study evaluations within six months of initiation of their AMP 2.5 and 4.5 year study visits. The improved survival of children infected perinatally with HIV, and the aging of the cohort into adulthood, raises clinical and public health issues related to their ability to assume productive independent lives as adults. Existing literature suggests that these youth may have developmental cognitive deficits that have the potential to affect their day-to-day functioning. In adults with HIV, impairments in memory, particularly prospective memory (ProM), and executive functioning (EF) are among the most significant predictors of poor functional outcomes. We hypothesize that children and youth with perinatally-acquired HIV will experience similar effects. In fact, children and adolescents, who are in the process of learning both academic and nonacademic skills, and at a time of rapid change in EF, may show an even greater impact of memory and EF deficits on everyday living than adults, who usually have acquired basic life skills. Understanding the impact on academic functioning, a primary task of adolescence and critical for adult success, is particularly important. To date, no well-controlled studies of perinatally infected children or youth have included comprehensive assessments of retrospective memory or EF, or any measures of ProM. Furthermore, the studies that have assessed memory or EF have not examined their association with academic or adaptive outcomes or medication adherence. The purpose of this study is to fill this significant gap in our knowledge by examining retrospective memory, ProM and EF in a large, well-characterized sample of perinatally infected children and adolescents and matched controls age 9 years to 19 years at study entry. The study goals include an evaluation of the presence and pattern of memory and EF deficits in HIV-infected children compared to controls and their relationship with HIV disease severity, the interrelationship of change in these functions with normal development and changes in disease severity, and whether memory and EF predict medication nonadherence and academic or adaptive problems. Well-standardized measures of memory and EF will be used, and two measures of ProM will be included, one previously used with children and one an adaptation for children of an adult measure of ProM with known associations with HIV. In addition to focusing on functional domains about which we have limited information for this population, the study will represent the first longitudinal research in this area. This will allow us to begin to disentangle developmental and HIV-related changes, both disease progression and improvement with treatment. The linkage of this protocol with PHACS AMP enables us to examine and control for important covariates and to conduct exploratory analyses without additional expense and with minimal burden for research participants. Detailed medication information maintained by PHACS may also allow exploratory examination of changes related to specific drug classes, including CNS penetrance, if sufficient variability in regimens exists in our sample. We anticipate that the study will not only elucidate the developmental cognitive impact of perinatally acquired HIV infection but also will have implications for predicting poor functional outcomes in perinatally infected youth as they approach adulthood. Both memory and EF domains are critically involved in performance of daily activities and in achieving academic and occupational competence. Thus, the study has the potential to have significance for evaluation of infected youth and support the inclusion of memory and EF testing in neuropsychological assessments as standard of care for this population. It would enable care providers and schools to target intervention resources more effectively towards youth with cognitive deficits. The research findings would also set the stage for future studies in the areas of cognitive and adherence intervention, prediction of increased risk behaviors, and central nervous system effects of perinatal HIV by further clarifying developmental patterns of retrospective and ProM and EF associated with the disease. Finally, the study has the potential to contribute an innovative measure of ProM to the pediatric literature. All participants in the study will be monitored from the time of the consent until the final study visit is completed. Untoward effects identified as 1) those related to the participant including social harms, psychological distress, and serious life threatening events such as suicide attempts, 2) those related to the study staff, and (3) those related to the neighborhood/community, if applicable, will be monitored. All untoward effects will be addressed, evaluated, and guidance provided to minimize similar risks in others.

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。 这项研究是一项前瞻性队列研究，比较了两组青少年（研究开始时年龄为 9 岁至 19 岁）的记忆和执行功能：一组是围产期感染人类免疫缺陷病毒 (HIV)-1 的青少年，另一组是感染人类免疫缺陷病毒 (HIV)-1 的青少年。围产期暴露于 HIV-1 但未感染的青少年。 所有注册的青少年目前都将参加 PHACS AMP。 至少 275 名可评估参与者（200 名 HIV-1 感染者和 75 名 HIV-1 暴露、未感染者）将被纳入。 参与者将被跟踪两年，并将在 AMP 2.5 和 4.5 年研究访问开始后的六个月内接受研究评估。 围产期感染艾滋病毒的儿童的生存率有所提高，并且该人群进入成年期的老龄化，引发了与他们成年后过上富有成效的独立生活的能力相关的临床和公共卫生问题。 现有文献表明，这些年轻人可能存在发育性认知缺陷，有可能影响他们的日常功能。 在感染艾滋病毒的成年人中，记忆障碍，特别是前瞻性记忆（ProM）和执行功能（EF）损伤是功能结果不佳的最重要预测因素之一。 我们假设围产期感染艾滋病毒的儿童和青少年也会经历类似的影响。 事实上，儿童和青少年正处于学习学术和非学术技能的过程中，并且处于 EF 快速变化的时期，他们的记忆力和 EF 缺陷对日常生活的影响可能比成年人更大，成年人通常有获得了基本的生活技能。 了解对学业功能的影响尤为重要，学业功能是青春期的首要任务，对成人的成功至关重要。 迄今为止，还没有针对围产期感染儿童或青少年的良好对照研究包括对回顾性记忆或 EF 或任何 ProM 测量的综合评估。 此外，评估记忆力或 EF 的研究并未检验它们与学业或适应性结果或药物依从性的关联。 本研究的目的是通过检查大量、特征明确的围产期感染儿童和青少年样本以及研究开始时年龄为 9 岁至 19 岁的匹配对照样本的回顾性记忆、ProM 和 EF，来填补我们知识中的这一重大空白。 研究目标包括评估与对照组相比，艾滋病毒感染儿童的记忆和EF缺陷的存在和模式及其与艾滋病毒疾病严重程度的关系，这些功能的变化与正常发育和疾病严重程度变化的相互关系，以及是否记忆力和 EF 可以预测药物依从性以及学业或适应性问题。 将使用标准化的记忆和 EF 测量方法，并将包括两种 ProM 测量方法，一种以前用于儿童，另一种方法是针对已知与 HIV 相关的成人 ProM 测量方法进行改编。 除了关注我们对这一人群的信息有限的功能领域外，该研究还将代表该领域的首次纵向研究。 这将使我们能够开始理清发育和艾滋病毒相关的变化，包括疾病的进展和治疗的改善。 该协议与 PHACS AMP 的联系使我们能够检查和控制重要的协变量，并进行探索性分析，无需额外费用，并且对研究参与者的负担最小。 如果我们的样本中存在足够的治疗方案变异性，则 PHACS 维护的详细药物信息还可以允许探索性检查与特定药物类别相关的变化，包括 CNS 外显率。 我们预计这项研究不仅将阐明围产期艾滋病毒感染对认知发育的影响，而且还将对预测围产期感染艾滋病毒的青少年在接近成年时的不良功能结果产生影响。记忆和 EF 领域都与日常活动的表现以及获得学术和职业能力密切相关。因此，该研究有可能对受感染青少年的评估具有重要意义，并支持将记忆和 EF 测试纳入神经心理学评估中，作为该人群的护理标准。 它将使护理提供者和学校能够更有效地针对有认知缺陷的青少年提供干预资源。 研究结果还将通过进一步阐明与该疾病相关的回顾性以及 ProM 和 EF 的发育模式，为未来在认知和依从性干预、风险行为增加预测以及围产期 HIV 对中枢神经系统影响等领域的研究奠定基础。 最后，该研究有可能为儿科文献贡献一种创新的 ProM 测量方法。 从同意到最终研究访视完成，所有研究参与者都将受到监测。不良影响被确定为 1) 与参与者相关的影响，包括社会伤害、心理困扰和严重危及生命的事件，如自杀未遂，2) 与研究人员相关的影响，以及 (3) 与邻里/社区相关的影响，如果适用，将受到监控。 所有不良影响都将得到解决、评估，并提供指导，以尽量减少其他人的类似风险。