Improving identification of HIV-associated neurocognitive disorder (HAND) in Latin America: A multimodal approach to HAND in Peru

项目摘要 这是莫妮卡·M博士的K23奖申请书北方大学的神经学家迪亚兹说， 查佩尔山医学院的卡罗莱纳。迪亚兹博士正在建立自己作为一个研究者在病人为导向 拉丁美洲大脑健康和艾滋病交叉点的临床研究。迪亚兹医生至少有一半的时间- 自2019年以来，她一直在秘鲁工作，在那里她开展了一项指导性试点研究，评估艾滋病毒相关的神经认知功能。 在秘鲁，艾滋病毒感染者中的老年人患有手足综合症。K23奖将为迪亚兹博士提供必要的 支持发展5个关键领域的专业知识：1）定性研究方法和分析，2）临床工具 国际环境中的验证，3）神经心理学评估，4）高级生物统计技能，5） 实施科学框架和方法。迪亚兹博士组建了一个核心导师团队。 Gwenn Garden [神经认知障碍评估专家]、维克托瓦尔库尔博士[国际神经认知障碍评估专家] HAND评估]和克莱尔巴林顿博士[拉丁美洲混合方法/定性研究专业知识] 她将指导迪亚兹博士实现她的培训目标和职业发展。支持迪亚兹医生和她的核心 导师是三个合作者：玛丽亚马奎恩博士（神经心理学家与拉丁美洲人的手的专业知识），博士。 Michael Hudgens（具有HIV观察数据专业知识的生物统计学家）和Patricia Garcia博士 （秘鲁艾滋病毒问题执行科学专家）。这个多学科的导师团队嵌入在一个 高度合作的培训环境对于迪亚兹博士成为一名独立调查员至关重要 其目标是优化拉丁美洲艾滋病毒感染者大脑健康的诊断和治疗。 HAND是中低收入国家的一个紧迫问题，因为抗逆转录病毒治疗的可及性日益增加 治疗，强调迫切需要优化诊断和预测手早期干预。博士 迪亚兹在这份申请中概述的研究计划利用了试点数据，这些数据表明，近30%的人 利马的艾滋病毒感染者患有HAND，但由于缺乏区域 神经心理学测试的规范性数据和专家。拟议的研究包括一个前瞻性队列 艾滋病毒感染者和艾滋病毒阴性对照者来自利马两个社会经济状况不同的艾滋病毒诊所。研究 旨在调整和验证目前针对早期阿尔茨海默氏症优化的基于平板电脑的认知筛查工具 在秘鲁进行HAND筛查（目标1）。认知障碍的已知可改变风险因素，包括 健康的社会决定因素，将用于建立秘鲁的HAND预测统计模型， 可干预因素（目标2）。这两个工具将通过迭代来实现、评估和优化 与艾滋病毒护理提供者进行多轮访谈（目标3）。这个K23奖将为迪亚兹博士提供指导 和专业知识，成为一个独立的调查，以改善大脑健康的不足 拉丁美洲的艾滋病毒感染者。这一提议是朝着开发一个大的前景迈出的关键一步。 研究确定拉丁美洲HAND的频率和风险因素，作为未来的R 01赠款。

PROJECT SUMMARY This is an application for a K23 award for Dr. Monica M. Diaz, a neurologist at the University of North Carolina at Chapel Hill School of Medicine. Dr. Diaz is establishing herself as an investigator in patient-oriented clinical research at the intersect of brain health and HIV in Latin America. Dr. Diaz has been based at least half- time in Peru since 2019 where she developed a mentored pilot study assessing HIV-associated neurocognitive disorder (HAND) in older people living with HIV in Peru. The K23 award will provide Dr. Diaz with the necessary support to develop expertise in 5 key areas: 1) Qualitative research methods and analysis, 2) clinical tool validation in international settings, 3) neuropsychological assessments, 4) advanced biostatistical skills, 5) implementation science frameworks and methodology. Dr. Diaz has assembled a team of core mentors (Dr. Gwenn Garden [expert in neurocognitive disorder assessments], Dr. Victor Valcour [expert in international assessments of HAND] and Dr. Clare Barrington [mixed-methods/qualitative research expertise in Latin America] who will guide Dr. Diaz in achieving her training goals and career development. Supporting Dr. Diaz and her core mentors are three collaborators: Dr. Maria Marquine (neuropsychologist with expertise in HAND in Latinos), Dr. Michael Hudgens (biostatistician with expertise in HIV observational data) and Dr. Patricia Garcia (implementation science expert on HIV in Peru). This multi-disciplinary mentorship team embedded within a highly collaborative training environment is crucial for Dr. Diaz’s development into an independent investigator with the goal of optimizing diagnostics and treatments for brain health in people with HIV in Latin America. HAND is a pressing issue in low-and-middle-income countries with increasing access to antiretroviral therapy, highlighting the urgent need to optimize diagnostics and prediction of HAND for early interventions. Dr. Diaz’s research plan outlined in this application leverages pilot data that demonstrated that nearly 30% of people living with HIV in Lima had HAND, yet diagnostics for HAND are limited in Latin America given a lack of regional normative data and experts in neuropsychological testing. The proposed research includes a prospective cohort of patients with HIV and HIV-negative controls from two socioeconomically-distinct HIV clinics in Lima. The study seeks to adapt and validate a tablet-based cognitive screening tool currently optimized for early Alzheimer’s screening to detect HAND in Peru (Aim 1). Known modifiable risk factors for cognitive impairment, including social determinants of health, will be used to build a predictive statistical model for HAND in Peru that can identify intervenable factors (Aim 2). These two tools will be implemented, evaluated and optimized through iterative rounds of interviewing with HIV care providers (Aim 3). This K23 award will provide Dr. Diaz with the mentorship and expertise necessary to become an independent investigator to improve brain health of underserved populations with HIV in Latin America. This proposal is a crucial step toward developing a large prospective study identifying frequency and risk factors for HAND in Latin America as a future R01 grant.