Mental Health and Cognition in HIV Infection in Rakai Uganda

乌干达拉凯艾滋病毒感染者的心理健康和认知

• 批准号: 10000143
• 负责人: Robert H Paul
• 金额: $ 58.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-22 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000143
• 关键词: Acute; Address; Adherence; Affect; Affective; Africa; Africa South of the Sahara; Alcohol or Other Drugs use; Anti-Anxiety Agents; Antidepressive Agents; Basic Science; Behavioral; Biological; Biological Markers; Biology; Brain; Categories; Cerebrovascular Disorders; Clinical Trials; Cocaine; Cognition; Cognitive; Cognitive Therapy; Cohort Studies; Complex; Data; Diabetes Mellitus; Dimensions; Disease; Emotions; Enrollment; Exposure to; Fright; Functional disorder; Funding; HIV; HIV Infections; HIV Seronegativity; HIV-associated neurocognitive disorder; Hepatitis C co-infection; Heterogeneity; Hypertension; Impairment; Individual; Inflammation; Infrastructure; Insulin; Intervention; Investigation; Knowledge; Lead; Learning; Literature; Longitudinal cohort; Major Depressive Disorder; Measures; Memory; Mental Depression; Mental Health; Mental disorders; Methodology; Motor; NIH Office of AIDS Research; Narcotics; National Institute of Mental Health; Negative Valence; Nervous System Physiology; Neuraxis; Neurocognitive Deficit; Neurology; Neurons; Neuropsychological Tests; Obesity; Outcome; Participant; Pathogenesis; Pattern; Pharmaceutical Preparations; Phenotype; Population; Research; Research Domain Criteria; Research Personnel; Research Priority; Risk Factors; Rural; Symptoms; System; Therapeutic Intervention; Thinking; Trauma; Treatment/Psychosocial Effects; Uganda; United States; United States National Institutes of Health; Violence; Viral reservoir; Visit; Women’s Interagency HIV Study; accurate diagnosis; antiretroviral therapy; axon injury; base; behavioral phenotyping; biomarker panel; clinically significant; cognitive control; cohort; comorbidity; cost; depressive symptoms; exosome; hypercholesterolemia; illicit drug use; improved; inflammatory marker; low income country; motor disorder; neurofilament protein L; novel; outcome forecast; preservation; psychosocial; targeted treatment; therapy adherence

Mental health disorders including depression and neurocognitive impairment (NCI) are the most common central nervous system (CNS) complications of HIV infection despite effective antiretroviral therapy (ART). It is estimated that 40-50% of HIV+ individuals have at least one mental health disorder. Uganda, a low-income country in Sub- Saharan Africa (SSA) has ~1.5 million people living with HIV (PLWH) many of whom are on ART. Despite ART use, CNS complications, which are notably heterogeneous, persist among PLWH. Uganda provides a unique setting for advancing our understanding of major depressive disorder [MDD] and NCI, because common confounding conditions in the United States such as cerebrovascular disease risk factors and illicit drug use (e.g., narcotics, cocaine) are rare in Uganda. We propose to address the overarching hypothesis that there is substantial heterogeneity in MDD and NCI in PLWH and that psychosocial determinants (e.g., sexual and physical trauma, violence) are likely contributors to this heterogeneity. Addressing the heterogeneity in MDD and NCI is critical to advancing our understanding of cognitive phenotypes. To accomplish our aims, we will use a novel methodology for mental health in HIV research, the NIMH Research Domain Criteria (RDoC) framework, which recognizes heterogeneity, to first examine behavioral phenotypes among PLWH followed by studies to understand the functional consequences of these phenotypes and the underlying pathophysiology in these phenotypes. Our study results should lead to more accurate diagnosis, prognosis, and targeted interventions for MDD and NCI in HIV infection globally. We plan to cost-effectively leverage the established infrastructure and data from our previous Rakai Neurology Cohort Study to examine the following aims: Aim 1: Examine separate and interactive effects of HIV and psychosocial determinants on CNS dysfunction in PLWH. Hyp 1. Exposure to sexual/physical trauma or violence will interact with HIV in this population and will be associated with greater impairments/decline in declarative memory, cognitive control, and NVS. Aim 2: Examine effects of psychosocial determinants and CNS dysfunction on ART adherence in PLWH. Hyp 2. Exposure to sexual/physical trauma or violence and/or impairments/decline in declarative memory, cognitive control, and NVS will adversely affect ART adherence. Exploratory Aim 3: Determine biomarkers that relate most strongly and reliably to CNS dysfunction in the context of HIV and/or psychosocial determinants. Hyp 3: Different biomarkers of neuronal damage and CNS inflammation will relate to patterns of impairment/decline in declarative memory, cognitive control, motor, and NVS in the context of HIV and/or exposure to sexual/physical trauma or violence. We will also build capacity to evaluate and conduct research in mental health disorders and introduce new measures of adherence to our cohort. Our proposal addresses several high priority research topics for the NIH Office of AIDS Research including HIV-associated comorbidities, basic research to understand the pathogenesis of mental health disorders in HIV infection, and research to identify viral reservoirs that could lead to a cure for HIV infection.

包括抑郁症和神经认知障碍 (NCI) 在内的精神健康障碍是最常见的中枢疾病 尽管进行了有效的抗逆转录病毒治疗（ART），但 HIV 感染的神经系统（CNS）并发症。估计 40-50% 的 HIV 感染者至少患有一种精神健康障碍。乌干达是一个低收入国家 撒哈拉非洲 (SSA) 约有 150 万艾滋病毒感染者 (PLWH)，其中许多人正在接受抗逆转录病毒治疗。尽管有艺术 使用中，中枢神经系统并发症在 PLWH 中持续存在，其明显异质性。乌干达提供了独特的 提高我们对重度抑郁症 [MDD] 和 NCI 的理解的环境，因为常见 美国的混杂情况，例如脑血管疾病危险因素和非法药物使用（例如， 麻醉品、可卡因）在乌干达很少见。我们建议解决一个总体假设： PLWH 中的 MDD 和 NCI 存在显着异质性，并且社会心理决定因素（例如性和身体因素） 创伤、暴力）可能是造成这种异质性的原因。解决 MDD 和 NCI 的异质性是 对于增进我们对认知表型的理解至关重要。为了实现我们的目标，我们将使用一部小说 HIV 研究中心理健康的方法论，NIMH 研究领域标准 (RDoC) 框架， 认识到异质性，首先检查 PLWH 中的行为表型，然后进行研究 了解这些表型的功能后果以及这些表型的潜在病理生理学 表型。我们的研究结果应该能够为患者提供更准确的诊断、预后和有针对性的干预措施 全球 HIV 感染中的 MDD 和 NCI。我们计划以具有成本效益的方式利用现有的基础设施和 来自我们之前的 Rakai 神经病学队列研究的数据，旨在检查以下目标： 目标 1：检查单独的 HIV 和心理社会决定因素对 PLWH 中枢神经系统功能障碍的交互影响。 Hyp 1. 暴露于 性/身体创伤或暴力将与该人群中的艾滋病毒相互作用，并与更大程度的感染相关。 陈述性记忆、认知控制和 NVS 受损/下降。目标 2：检查社会心理的影响 PLWH 中 ART 依从性的决定因素和 CNS 功能障碍。 Hyp 2. 遭受性/身体创伤或 暴力和/或陈述性记忆、认知控制和 NVS 损伤/下降将对 ART 产生不利影响 坚持。探索性目标 3：确定与中枢神经系统功能障碍最密切、最可靠相关的生物标志物 在艾滋病毒和/或心理社会决定因素的背景下。 Hyp 3：神经元损伤的不同生物标志物 中枢神经系统炎症与陈述性记忆、认知控制、运动、 以及在艾滋病毒和/或遭受性/身体创伤或暴力的情况下的 NVS。我们还将进行能力建设 评估和开展精神健康障碍的研究，并引入新的措施来遵守我们的 队列。我们的提案涉及 NIH 艾滋病研究办公室的几个高度优先的研究主题，包括 HIV 相关合并症，了解 HIV 精神健康障碍发病机制的基础研究 感染，并进行研究以确定可能治愈艾滋病毒感染的病毒库。