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

基本信息

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
项目类别：
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

项目摘要

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) 是美国常见的 HIV 神经系统并发症，我们的初步数据表明，乌干达 31% 的 HIV+ 个体可能患有 HIV 痴呆，这是 HAND 的最严重阶段。 HIV 相关的精神疾病也很常见，也有证据表明，在患有晚期免疫抑制的个体中，HIV D 亚型与 A 亚型相比，与更常见的神经认知疾病相关。乌干达的 Rakai 健康科学计划 (RHSP) 为开展此类研究提供了独特的机会，可以识别中度 (CD4 350-500) 和更严重的 HIV+ 个体。 (CD4 ≤200) 来自其人群队列和艾滋病毒诊所服务的免疫抑制，拉凯区也是异性恋流行病涉及不同艾滋病毒亚型的少数地区之一。重组体），使我们能够比较亚型对合并症的影响： 1. 在基线时，评估 20 岁以上未接受 ART 的 HIV+ 成人是否患有中度免疫抑制（CD4 350-500）和高级免疫抑制（CD4 ≤）。 200) 与同一拉凯地区年龄和性别匹配的艾滋病毒成人相比，经历了关键的神经认知/精神共病，并且功能状态下降人口（后者将提供乌干达农村地区尚未获得的规范数据），2. 根据 HIV 亚型和治疗前后的免疫抑制水平，评估 HIV+ 患者在两年随访中这些合并症的轨迹ART 启动，以及 3. 确定按 HIV 亚型分层的患有和不患有痴呆症的个体的 CSF 中的区室化病毒水平假设： 1. 患有中度和严重免疫抑制的未接受 ART 的 HIV+ 个体具有更高的病毒水平。与同一社区的 HIV 感染者相比，神经认知/精神疾病和功能障碍的患病率和严重程度，2。ART 将降低合并症的患病率和严重程度，但比率仍将显着高于 HIV 感染者，3 HIV+ 患者的神经系统合并症，无论是否接受 ART，都会对功能状态产生不利影响，增加健康和社会支持需求，4。 HIV D 亚型与个体中的 A 亚型相比，与痴呆风险加速相关5. 脑脊液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程度更高。该研究将为制定与神经认知/精神共病相关的预防和支持计划提供流行病学和临床数据，以及 HIV 相关中枢神经系统病理学的机制数据。