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

全世界有210万15岁以下的儿童感染艾滋病毒（CWH），其中绝大多数人 围产期获得的艾滋病毒，居住在资源有限的低收入和中等收入国家（LMIC）， 存活到青春期和成年早期。在乌干达，拟议的研究将在那里进行， 15岁以下的儿童超过130，000 CWH。CWH必须应对终身病毒感染的负面影响 和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， 终身坚持抗逆转录病毒治疗的要求-使他们处于无法实现关键发展里程碑的风险之中。 神经认知功能障碍（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可以影响 儿童在学校的表现和完成学业的能力，与同龄人和成年人成功互动的能力， 保持长期关系，培养独立性。NCI也会干扰对 药物，这是艾滋病毒的关键，并增加了不良决策和更大的艾滋病毒传播风险 行为（例如，无保护措施的性行为）。在CWH中解决NCI的第一步 但在乌干达这样做面临着许多挑战。很少有神经认知测试存在乌干达 5-12岁的儿童。现有的测试需要训练有素的人员来管理和评分， 需要几个小时来管理，许多人遭受文化偏见，因为他们是为和 在美国或欧洲的年轻人身上。如果没有准确的、临床上有用的和相对简短的NCI评估， 能够由各级工作人员、研究人员和临床医生准确管理的药物仍然非常有限 在乌干达评估CWH的能力，错过了研究和发现NCI的机会，以及 介入NeuroScreen是一款简单易用的Android设备应用程序，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12个神经认知测试， 速度、执行功能、工作记忆、文字记忆和运动速度。它是标准化的， 自动化，需要最少的培训来管理，并且不需要记录或评分。已经 成功用于成人和青少年，但尚未评估用于13岁以下儿童 年拟议的研究将：（1）确定使NeuroScreen可用所需的必要调整， 13岁以下的CWH和可能管理它的HIV提供者可以理解和接受;（2） 在CHW和匹配的对照组中生成适应性测试的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 数据将是未来更大规模的NCI研究的基础，以及验证，实施和 在乌干达和其他中低收入国家推广这一移动保健工具。

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.