Neurologic Sequelae of HIV Subtype A and D Infection and ART Rakai Uganda

HIV A 和 D 亚型感染和 ART 的神经系统后遗症 Rakai 乌干达

• 批准号: 9235631
• 负责人: NED C SACKTOR
• 金额: $ 14.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9235631
• 关键词: 20 year old; AIDS Dementia Complex; Activities of Daily Living; Address; Adult; Affect; Africa; Africa South of the Sahara; African; Age; Blood; CD4 Lymphocyte Count; Caring; Cells; Cerebrospinal Fluid; Chronic Disease; Clinic; Clinical; Clinical Data; Cohort Studies; Communicable Diseases; Communities; Comorbidity; Complication; Data; Dementia; Developed Countries; Development; Environmental Risk Factor; Epidemic; Epidemiology; Europe; Gender; Genetic Predisposition to Disease; HIV; HIV Infections; HIV Seropositivity; HIV-associated neurocognitive disorder; Health; Health Sciences; Health Services; Heterosexuals; High Prevalence; Immunosuppression; Individual; Infection; Intervention; Interview; Laboratories; Long-Term Care; Low Prevalence; Morbidity - disease rate; Neurocognitive; Neurologic; Outcome; Participant; Pathogenesis; Pathology; Patients; Persons; Population; Prevalence; Prevention; Recombinants; Research; Risk; Role; Rural; Sampling; Services; Severities; Social support; Staging; Testing; Time; Uganda; Viral; Virus; aged; antiretroviral therapy; cohort; depressive symptoms; disability; disorder subtype; experience; follow up assessment; follow-up; functional disability; functional status; insight; lifestyle factors; neurocognitive disorder; population based; programs; treatment program; virus genetics

DESCRIPTION (provided by applicant): HIV associated neurocognitive disorder (HAND) is a common neurological complication of HIV in the US, and our preliminary data suggest that 31% of HIV+ individuals in Uganda may have HIV dementia, the most severe stage of HAND. HIV- associated psychiatric morbidity is also common. There is also evidence that HIV subtype D is associated with more prevalent neurocognitive morbidity than subtype A in individuals with advanced immunosuppression. However, there are no large population based studies of the neurocognitive or psychiatric status of HIV+ African individuals. The Rakai Health Sciences Program (RHSP), Uganda, offers a unique opportunity to conduct such research. The RHSP can identify HIV+ individuals with moderate (CD4 350-500) and more severe (CD4 ≤200) immunosuppression from its population based cohort and HIV clinic services. Rakai District is also one of the few regions where a heterosexual epidemic involves different HIV subtypes (A, D, recombinants), enabling us to compare subtype effects on co-morbidities. Specific aims are: 1. At baseline, to assess whether ART naïve HIV+ adults aged ≥ 20 years with moderate immunosuppression (CD4 350-500), and advanced immunosuppression (CD4 ≤ 200) experience key neurocognitive/psychiatric co-morbidities, and reduced functional status, compared to age and gender matched HIV- adults in the same Rakai population (the latter will provide normative data as yet unavailable in rural Uganda), 2. To assess the trajectory of these co-morbidities in the HIV+s at two years of follow-up by HIV subtype and level of immunosuppression prior to and after ART initiation, and 3. To define the level of compartmentalized virus in the CSF of individuals with and without dementia stratified by HIV subtype. Hypotheses: 1. ART naïve HIV+ individuals with moderate and advanced immunosuppression have higher prevalence and severity of neurocognitive/psychiatric morbidity, and functional disability, compared to HIV- persons in the same communities, 2. ART will reduce the prevalence and severity of co-morbidities, but rates will remain significantly higher than in HIV- persons, 3. Neurological co-morbidities in HIV+ persons, whether or not they are on ART, adversely affect functional status, increasing health and social support needs, 4. HIV subtype D is associated with an accelerated risk of dementia than subtype A among individuals with advanced immunosuppression, 5. Greater viral genetic compartmentalization in the CSF correlates with dementia and is increased with subtype D compared to A. The study will provide epidemiological and clinical data for the development of prevention and support programs related to neurocognitive /psychiatric co-morbidities, and mechanistic data on HIV-related CNS pathology.

描述（由申请人提供）：HIV相关神经认知障碍（HAND）是美国HIV常见的神经系统并发症，我们的初步数据表明，乌干达31%的HIV阳性个体可能患有HIV痴呆，这是HAND最严重的阶段。与艾滋病毒有关的精神病发病率也很常见。也有证据表明，在晚期免疫抑制的个体中，HIV亚型D比亚型A与更普遍的神经认知发病率相关。然而，目前还没有针对艾滋病毒+非洲个体的神经认知或精神状态的大规模人群研究。乌干达的Rakai健康科学方案为开展此类研究提供了一个独特的机会。RHSP可以从其基于人群的队列和艾滋病毒诊所服务中识别中度（CD 4 350-500）和更严重（CD 4 ≤200）免疫抑制的艾滋病毒阳性个体。Rakai区也是少数几个异性恋流行病涉及不同艾滋病毒亚型（A，D，重组体）的地区之一，使我们能够比较亚型对合并症的影响。 具体目标是：1。在基线时，为了评估与相同Rakai人群中年龄和性别匹配的HIV-成人相比，年龄≥ 20岁、中度免疫抑制（CD 4 350-500）和晚期免疫抑制（CD 4 ≤ 200）的ART初治HIV+成人是否经历关键的神经认知/精神共病和功能状态降低（后者将提供乌干达农村尚未获得的规范性数据），2.通过HIV亚型和ART启动前后的免疫抑制水平，评估HIV+患者在2年随访时这些合并症的轨迹; 3.确定按HIV亚型分层的痴呆和非痴呆个体CSF中区室化病毒的水平。 假设：1.与同一社区的艾滋病毒感染者相比，接受过ART治疗且患有中度和重度免疫抑制的艾滋病毒+患者的神经认知/精神疾病和功能障碍的患病率和严重程度更高，2。抗逆转录病毒疗法将降低合并症的患病率和严重程度，但发病率仍将显著高于艾滋病毒感染者，3。HIV+患者的神经系统合并症，无论是否接受抗逆转录病毒治疗，都会对功能状态产生不利影响，增加健康和社会支持需求。在晚期免疫抑制的个体中，HIV亚型D与痴呆的风险比亚型A更快相关，5。CSF中更大的病毒遗传区室化与痴呆相关，并且与A亚型相比，D亚型的病毒遗传区室化增加。该研究将提供流行病学和临床数据，用于制定与神经认知/精神病共病相关的预防和支持计划，以及HIV相关CNS病理学的机制数据。