Building Resources to Assess Impaired Neurocognition in Children with HIV in Low- and Middle-Income Countries (BRAIN Child in LMICs)

全球有 210 万 15 岁以下的艾滋病毒儿童 (CWH)；绝大多数人都有 围产期获得的艾滋病毒居住在资源有限的中低收入国家 (LMIC)，并且 存活到青春期和青年期。提议的研究将在乌干达进行 15 岁以下超过 130,000 CWH。 CWH 必须应对终生病毒感染的负面影响 慢性炎症对他们的神经发育、医疗状况、心理健康以及对许多人来说 终生坚持 ART 的要求——使他们面临无法实现关键发展里程碑的风险。 神经认知障碍（NCI）是这些负面影响中最主要的。 CWH 中的 NCI 最常影响 工作记忆、执行功能和处理速度的神经认知领域。 NCI 可能会影响 儿童在学校表现并完成学业、与同龄人和成人成功互动、发起和完成学业的能力 维持长期关系，并培养独立性。 NCI 也会干扰遵守 药物治疗对艾滋病毒至关重要，并且会增加决策失误和艾滋病毒传播风险 年龄较大的儿童和青少年的行为（例如无保护的性行为）。 CWH 解决 NCI 问题的第一步 正在检测它，但在乌干达这样做面临着许多挑战。乌干达的神经认知测试很少 5-12岁儿童。确实存在的测试需要训练有素的人员来管理和评分， 管理起来需要几个小时，而且许多人都受到文化偏见的困扰，因为它们是为以下目的而开发的： 对美国或欧洲的年轻人进行规范。缺乏准确、有临床意义且相对简短的 NCI 评估 各级工作人员、研究人员和临床医生能够准确管理的信息仍然受到严重限制 评估乌干达 CWH 的能力，错过了研究和检测 NCI 的机会，以及 干预。 NeuroScreen 是一款简短、易于使用的应用程序，适用于 Android 设备，用于评估 NCI，旨在 由各级临床工作人员管理。该应用程序包含十二个评估处理的神经认知测试 速度、执行功能、工作记忆、言语记忆和运动速度。它标准化且高度 自动化，需要最少的管理培训，并且不需要记录或评分。已经是 已成功用于成人和青少年，但尚未针对 13 岁以下儿童进行评估 年。拟议的研究将：（1）确定使 NeuroScreen 可用所需的必要调整， 对于 13 岁以下的 CWH 以及可能进行管理的 HIV 提供者来说是可以理解和接受的； (2) 生成 CHW 和匹配对照中适应测试有效性指标的初步估计 5-12 年龄； (3) 探索 NeuroScreen 表现与行为健康之间的关联。这些 数据将成为未来更大规模 NCI 研究以及验证、实施和实施的基础 扩大这一移动医疗工具在乌干达和其他中低收入国家的使用。

There are 2.1 million children with HIV (CWH) under 15 years of age worldwide; the vast majority have perinatally-acquired HIV, reside in resource limited Low-and-Middle Income Countries (LMICs), and are surviving into adolescence and young adulthood. In Uganda, where the proposed study will take place, there are over 130,000 CWH under 15 years. CWH must contend with the negative effects of life-long viral infection and chronic inflammation on their neurodevelopment, medical status, mental health, and, for many, the demands of lifelong ART adherence – placing them at risk for not achieving crucial developmental milestones. Neurocognitive impairment (NCI) is chief among these negative effects. NCI in CWH most commonly affects the neurocognitive domains of working memory, executive functions, and processing speed. NCI can affect children’s ability to perform in and complete school, interact successfully with peers and adults, initiate and maintain long-term relationships, and develop independence. NCI can also interfere with adherence to medication, which is critical in HIV, and increase poor decision-making and greater HIV transmission risk behaviors (e.g., unprotected sex) for older children and adolescents. The first step in addressing NCI in CWH is detecting it but doing so in Uganda faces numerous challenges. Few neurocognitive tests exist for Ugandan children 5-12 years of age. The tests that do exist require highly trained personnel to administer and score, take several hours to administer, and many suffer from cultural biases because they were developed for and normed on youth in the US or Europe. Without accurate, clinically useful, and relatively brief NCI assessments that can be administered accurately by all levels of staff, researchers and clinicians will remain severely limited in their capacity to assess CWH in Uganda, missing opportunities to study and detect NCI, as well as intervene. NeuroScreen is a brief, easy-to-use app for Android devices to assess for NCI that is designed to be administered by all levels of clinical staff. The app contains twelve neurocognitive tests assessing processing speed, executive functions, working memory, verbal memory, and motor speed. It is standardized and highly automated, requires minimal training to administer, and does not require record-keeping or scoring. It has been used successfully with adults and adolescents but has not been evaluated for use with children under 13 years. The proposed study will: (1) determine the necessary adaptations needed to make NeuroScreen usable, understandable, and acceptable to CWH under 13 years, and for HIV providers likely to administer it; (2) generate preliminary estimates of the adapted tests’ validity indicators among CHW and matched controls 5-12 years of age; and (3) explore associations between NeuroScreen performance and behavioral health. These data will be the basis for future larger-scale research studies on NCI, as well as validation, implementation and scale-up of this mHealth tool for use in Uganda and other LMICs.