Memory Functioning in Children and Adolescents with Perinatal HIV Infection

描述(申请人提供)：目前的治疗方法已将艾滋病毒/艾滋病从一种不可避免的致命疾病转变为一种通常被视为慢性病的疾病。许多出生时感染艾滋病毒的儿童，以前寿命很短，现在可以活到成年。这就需要更充分地了解这些青年在成为独立、富有成效的成年人方面遇到的障碍。在成年人中，艾滋病毒通常与记忆和执行功能(如抑制、认知灵活性和解决问题)的损害有关，这增加了日常功能问题的风险，包括不坚持用药。然而，对感染艾滋病毒的儿童和青年的记忆和执行功能的研究极其有限，而且没有一项研究包括前瞻性记忆(即执行未来意图的能力)的测量，这是对感染艾滋病毒的成年人日常功能的特别有力的预测。此外，我们目前对艾滋病毒对大脑发育的功能影响的了解有限。在此提出的这项研究将是第一次在重要功能结果的背景下评估发育和艾滋病毒感染对记忆和执行功能的复杂相互作用，以努力促进儿科神经艾滋病的临床科学。这项研究将检验以下假设：1)围产期获得的艾滋病毒与记忆和执行功能障碍有关；2)艾滋病毒的严重程度和病史，包括疾病最严重的年龄，将与记忆和执行功能的损害程度有关；3)发育变化和艾滋病毒严重程度的变化将随着时间的推移相互作用，影响这些功能；以及4)记忆和执行功能的损害导致日常功能问题(包括服药依从性、学习成绩和适应行为)。使用纵向设计来检查和控制青春期这些功能的发展变化，我们将在两个时间点，相隔两年，对200名9-18岁的艾滋病毒感染者和75名未感染艾滋病毒的青年进行言语和非言语的回顾记忆、前瞻性记忆、执行功能和药物依从性的测量。数据将在参与围产期艾滋病毒感染结局的大型全国性纵向研究的八个地点收集，这项研究是儿童艾滋病毒/艾滋病队列研究青少年主协议，从而使我们能够在围产期艾滋病毒感染的人口、健康、认知和行为方面的更大背景下，以高效和经济高效的方式检查记忆和执行功能。这是一个重要的调查领域，因为艾滋病毒感染者的记忆和执行功能缺陷可能会对他们在成年后获得健康和药物管理技能、适应和学习功能、行为以及最终的社会和职业结果产生广泛的影响。我们预计，这项研究不仅将阐明围产期获得性艾滋病毒的发育神经认知方面，而且还将提供重要信息和额外工具，以针对围产期感染艾滋病毒的青少年功能预后不良的风险进行干预。 公共卫生相关性：这项研究将评估出生前或出生期间获得的艾滋病毒感染对儿童和青少年学习和回忆信息、记住执行未来任务以及管理自己的注意力和行为的能力的影响。这些数据将为我们提供宝贵的见解，让我们了解艾滋病毒对认知发展的影响，这些方面以前没有研究过。这项研究还将检查记忆和执行功能问题是否会影响关键领域的日常行为，如服药依从性，从而为设计未来有效的艾滋病毒感染青少年干预措施提供有用的信息。 优势 这项研究捕捉到了一个明确的儿童群体，他们已经参与了儿童艾滋病毒的纵向观察性研究-PHACS-AMP，因此，关于早期感染、ART方案、CD4/VL模式/最低值和疾病阶段的良好数据可用。 合作小组提出了一项非常详细的语言/功能/记忆认知评估(包括WRAML、语言学习、设计记忆、前瞻记忆、意图记忆、流利性、抑制/干扰控制、问题解决、工作记忆、认知灵活性、全球认知、语言和精神运动速度)，将在2.5年和4.5年的访问中对200名HIV-1感染者和75名未感染HIV-1病毒的儿童进行评估-这是一个具有详细评估的大样本。 调查人员已经修改了应用程序，以考虑到多次比较 弱点 这项研究是观察性的，涉及两个时间点--在一个子集的儿童中为评估子集提供更多的时间点，可以评估评估的一致性/稳定性，以及是否有特定的功能或儿童群体的功能/记忆变化更不稳定。 包括干预试验/研究，以增强记忆/功能，同时表征

DESCRIPTION (provided by applicant): Current treatments have transformed HIV/AIDS from an inevitably fatal disease to one commonly managed as a chronic illness. Many children born with HIV infection, who previously suffered brief life spans, are now surviving into adulthood. This creates the need to understand more fully the obstacles these youth encounter in becoming independent, productive adults. In adults, HIV commonly is associated with impairments in memory and executive functions (such as inhibition, cognitive flexibility, and problem solving), which increase the risk of problems in day-to-day functioning, including medication nonadherence. Studies of memory and executive functions in children and youth with HIV infection are extremely limited, however, and none have included measures of prospective memory (that is, the ability to execute a future intention), which is a particularly robust predictor of daily functioning in adults with HIV. Furthermore, our current understanding of the functional impact of HIV on brain development is limited. The study proposed here would be the first to evaluate the complex interplay between development and HIV infection on memory and executive functions in the context of important functional outcomes in an effort to advance the clinical science of pediatric neuroAIDS. The study will test the hypotheses that: 1) perinatally acquired HIV is associated with deficits in memory and executive functioning; 2) HIV severity and history, including age at greatest disease severity, will be associated with degree of impairment in memory and executive functioning ; 3) developmental change and changes in HIV severity will interact to influence these functions over time; and 4) impairments in memory and executive function contribute to problems in daily functioning (including medication adherence, academic achievement, and adaptive behavior). Using a longitudinal design to examine and control for developmental changes in these functions during adolescence, we will administer measures of verbal and nonverbal retrospective memory, prospective memory, executive functions, and medication adherence to 200 HIV-infected and 75 uninfected youth age 9-18 at two time points, two years apart. Data will be collected at eight sites participating in a large national, longitudinal study of outcomes of perinatal HIV infection, the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, thus allowing us to examine memory and executive functioning in an efficient and cost-effective manner in the larger context of demographic, health-related, cognitive, and behavioral aspects of perinatal HIV infection. This is an important area for investigation because deficits in memory and executive function in youth with HIV could have wide-ranging effects on their acquisition of health and medication management skills, adaptive and academic functioning, behavior, and, ultimately, social and occupational outcome in adulthood. We anticipate this study will not only elucidate developmental neurocognitive aspects of perinatally acquired HIV but will also provide important information and additional tools to target areas of intervention for perinatally HIV-infected youth at risk for poor functional outcomes. PUBLIC HEALTH RELEVANCE: This study will evaluate the effect of HIV infection acquired before or during birth on the ability of children and youth to learn and recall information, remember to perform future tasks, and manage their own attention and behavior. The data will give us valuable insight into the impact of HIV on aspects of cognitive development previously not studied. The study also will examine whether problems in memory and executive functioning affect day-to-day behavior in critical areas such as medication adherence, thus providing helpful information to design effective future interventions for youth with HIV. Strengths The study captures a well-defined population of children participating already in longitudinal observational pediatric HIV research - PHACS-AMP, thus, good data on early infection, ART regimens, CD4/VL patterns/nadir, and Stage of disease are available. The collaborative team has proposed an extremely detailed assessment of verbal/functional/memory cognition (including WRAML, verbal learning, design memory, prospective memory, memory for intentions, fluency, inhibition/interference control, problem solving, working memory, cognitive flexibility, global cognition, language, and psychomotor speed) to be conducted on 200 HIV-1 infected and 75 HIV-1 uninfected children at 2.5 and 4.5 year visits- this is a large sample size with detailed assessment. The investigators have revised the application to take into account multiple comparisons Weaknesses The study is observational and involves 2 time points - more timepoints in a subset of children for a subset of evaluations would allow assessment of consistency/stability of the assessments and whether there are specific functions or groups of children with more labile changes in function/memory. Including an intervention pilot/study to enhance memory/function while characterizing