Enhancing Research for Inflammation and Cognitive Health in Perinatally Acquired HIV (ENRICH PHIV)

全世界有210万0-15岁的儿童感染艾滋病毒;绝大多数在围产期感染艾滋病毒。 获得性艾滋病毒（PHIV），居住在资源有限的低收入和中等收入国家（LMIC）， 进入青春期和青年期。在乌干达，拟议的研究将在那里进行， 13万名15岁以下儿童感染艾滋病毒，其中绝大多数为PHIV， 15年以上的PHIV感染患有PHIV的青少年必须与终身病毒感染的负面影响作斗争， 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-使他们处于无法实现这些重要里程碑的风险之中。神经认知 在这些负面影响中，损伤（NCI）是最主要的。PHIV青年中的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可以影响年轻人的 在学校表现并完成学业的能力，与同龄人和成年人成功互动的能力，找到工作的能力， 并保持长期的关系，并独立运作。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，无保护的性行为）。解决PHIV青年NCI的第一步是检测和诊断它， 但在泰国这样做面临着许多挑战。对于乌干达年轻人来说，几乎没有神经认知测试， PHIV。现有的测试需要训练有素的人员来管理和评分，需要几个小时才能完成。 管理，许多人遭受文化偏见，因为它们是为青年制定的， 美国或欧洲。如果没有准确的、临床上有用的、相对简短的NCI评估， 由各级工作人员管理，研究人员和临床医生将严重限制他们的能力，以评估 乌干达的PHIV青年，失去了研究和检测NCI以及干预的机会。NeuroScreen 是一个简短，易于使用的应用程序的Android设备，以评估为NCI，旨在由所有管理 临床工作人员的水平。该应用程序包含10个神经认知测试，评估处理速度，执行 功能、工作记忆、言语记忆和运动速度。它是标准化和高度自动化的， 需要最少的培训来管理，并且不需要记录或评分。拟定研究 将：（1）为乌干达和讲卢甘达语的人口中感染PHIV的青年调整NeuroScreen，并评估 调整NeuroScreen在乌干达PHIV感染者和临床工作人员中的可用性和可接受性;（2） 生成适应测试的有效性指标的初步估计;（3）检查适应测试的有效性指标。 NeuroScreen在泰国PHIV青年和临床工作人员中的可用性和可接受性;以及（3）探索 NeuroScreen表现与炎症和免疫激活标志物之间的关联。这些 数据将成为未来NCI和炎症的大规模研究的基础，以及验证， 在乌干达和其他中低收入国家实施和扩大这一移动保健工具。

There are 2.1 million children 0-15 years of age living with HIV worldwide; the vast majority have perinatally acquired HIV (PHIV), 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 children under 15 years living with HIV, the vast majority with PHIV, and tens of thousands more living with PHIV over 15 years. Youth with PHIV 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 these important milestones. Neurocognitive impairment (NCI) is chief among these negative effects. NCI in PHIV youth most commonly affects the neurocognitive domains of working memory, executive function and processing speed. NCI can affect youth’s ability to perform in and complete school, interact successfully with peers and adults, find employment, initiate and maintain long-term relationships, and function independently. 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). The first step in addressing NCI in PHIV youth is detecting and diagnosing it, but doing so in Thailand faces numerous challenges. Few neurocognitive tests exist for Ugandan youth with PHIV. 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 accurately administered by all levels of staff, researchers and clinicians will be severely limited in their capacity to assess youth with PHIV 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 ten 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. The proposed study will: (1) adapt NeuroScreen for Uganda and Luganda-speaking populations youth with PHIV and evaluated the adapted NeuroScreen’s usability and acceptability among Ugandan youth with PHIV and clinical staff; (2) generate preliminary estimates of the adapted tests’ validity indicators; (3) examine the adapted NeuroScreen’s usability and acceptability among PHIV Thai youth and clinical staff; and (3) explore associations between NeuroScreen performance and markers of inflammation and immune activation. These data will be the basis for future larger-scale research studies on NCI and inflammation, as well as validation, implementation and scale-up of this mHealth tool for use in Uganda and other LMICs.