PH 201 MEMORY FUNCTIONING IN CHILDREN AND ADOLESCENTS WITH PERINATAL HIV

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项研究是一项前瞻性队列研究，比较了两组年轻人的记忆和执行功能，研究开始时的年龄在9岁到19岁之间：一组将是通过围产期获得的人类免疫缺陷病毒(HIV)-1感染的青年，另一组将是围产期接触HIV-1但未感染的青年。所有注册的青少年目前都将参加PHACS AMP。将至少招募275名可评估参与者(200名感染艾滋病毒-1的参与者和75名暴露于艾滋病毒-1的未感染的参与者)。参与者将接受为期两年的跟踪调查，并将在开始AMP2.5年和4.5年研究访问后的六个月内接受研究评估。 围产期感染艾滋病毒的儿童存活率的提高，以及这一群体进入成年期的老龄化，引发了与他们作为成年人承担富有成效的独立生活的能力有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认知缺陷，这可能会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，特别是前瞻记忆(PROM)和执行功能(EF)是功能结果差的最重要的预测因素之一。我们假设，患有围产期获得性艾滋病毒的儿童和青少年将经历类似的影响。事实上，儿童和青少年都在学习学习学术和非学术技能的过程中，在EF快速变化的时候，记忆和EF缺陷对日常生活的影响可能比成年人更大，成年人通常已经掌握了基本的生活技能。了解这对学习功能的影响尤为重要，这是青春期的首要任务，也是成年后取得成功的关键。到目前为止，还没有一项对围产期感染的儿童或青少年进行良好对照的研究，包括对回顾记忆或EF或任何胎膜早破测量的全面评估。此外，评估记忆力或EF的研究没有检查它们与学业或适应性结果或服药依从性的关系。 这项研究的目的是通过对围产期感染的儿童和青少年以及研究开始时9岁至19岁的匹配对照组的大样本进行回顾记忆、胎膜早破和EF来填补这一显著的知识空白。这项研究的目标包括评估HIV感染儿童与对照组相比记忆和EF缺陷的存在和模式，以及它们与HIV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，以及记忆和EF是否可以预测药物不依从性以及学习或适应问题。将使用标准化的记忆力和EF测量，并将包括两种胎膜早破测量方法，一种以前用于儿童，另一种用于儿童适应已知与艾滋病毒有关的胎膜早破成人测量。除了专注于我们对这一人群的有限信息的功能领域外，这项研究将是这一领域的第一次纵向研究。这将使我们能够开始理清发展和艾滋病毒相关的变化，包括疾病的进展和治疗后的改善。这一方案与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，而不需要额外的费用，对研究参与者来说负担最小。如果我们的样本中存在足够的方案变异性，由PHACS维护的详细药物信息也可能允许探索性地检查与特定药物类别相关的变化，包括中枢神经系统的透过性。 我们预计，这项研究不仅将阐明围产期获得性艾滋病毒感染对发育认知的影响，还将对预测围产期感染的青少年在接近成年期时的不良功能结局产生影响。记忆域和EF域都与日常活动的表现以及学习和职业能力的实现密切相关。因此，这项研究有可能对受感染青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，作为对这一人群的护理标准。这将使护理提供者和学校能够更有效地将干预资源用于有认知缺陷的青少年。研究结果还将通过进一步澄清与疾病相关的回顾和胎膜早破和胎膜早破的发展模式，为未来在认知和依从性干预、增加危险行为的预测以及围产期艾滋病毒对中枢神经系统的影响等领域的研究奠定基础。最后，这项研究有可能为儿科文献贡献一种创新的舞会措施。 这项研究的所有参与者将从同意之时起一直受到监控，直到最后一次研究访问完成。不良影响被确定为1)与参与者有关的不良影响，包括社会伤害、心理困扰和严重的生命威胁事件，如自杀未遂，2)与研究人员有关的不良影响，以及(3)与邻里/社区有关的不良影响(如果适用)将受到监控。将对所有不良影响进行处理、评估，并提供指导，以最大限度地减少其他方面的类似风险。

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.