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：
8649088
负责人：
NED C SACKTOR
金额：
$ 56.8万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-08 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8649088
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 Clinical Research Cohort Studies Communicable Diseases Communities Comorbidity Complication Data Dementia Developed Countries Development Disease Environmental Risk Factor Epidemic Epidemiology Ethics Committees Europe Gender Genetic Predisposition to Disease HIV HIV Infections HIV Seropositivity Health Health Sciences Health Services Heterosexuals High Prevalence Immunosuppression Individual Infection Institutes Institutional Review Boards Intervention Interview Laboratories Long-Term Care Low Prevalence Morbidity - disease rate Neurocognitive Neurologic Opportunistic Infections Outcome Participant Pathogenesis Pathology Patients Persons Population Prevalence Prevention Recombinants Research Research Institute Risk Role Rural Sampling Science Services Severities Social support Staging Testing Time Uganda Universities Viral Viral Load result Virus acronyms aged antiretroviral therapy cohort depressive symptoms disability disorder subtype experience follow up assessment follow-up functional disability functional status insight lifestyle factors population based programs public health relevance 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 na¿ve 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 na¿ve 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) 其基于人口的队列和艾滋病毒诊所服务的免疫抑制也是少数几个异性恋流行涉及不同艾滋病毒亚型的地区之一（A、D、重组体），使我们能够比较亚型对合并症的影响，具体目标是： 1. 在基线时评估 ART 是否适用。 5 岁艾滋病病毒感染者 + 成年人 ¿与相同 Rakai 人群中年龄和性别匹配的 HIV 成人（后者将提供乌干达农村地区尚未提供的规范性数据），2. 评估 HIV+ 患者在两年的 HIV 随访中这些合并症的轨迹ART 启动之前和之后的免疫抑制亚型和水平，以及 3. 定义按 HIV 亚型分层的患有和不患有痴呆症的个体 CSF 中的区室病毒水平假设： 1. ART na¿与同一社区中的 HIV 感染者相比，患有中度和重度免疫抑制的 HIV 感染者具有更高的神经认知/精神发病率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，但比率会降低。仍然高于 HIV 感染者，3. HIV 感染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在患有晚期免疫抑制的个体中，D 亚型比 A 亚型与痴呆风险增加相关，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。该研究将为以下疾病提供流行病学和临床数据：制定与神经认知/精神共病相关的预防和支持计划，以及艾滋病毒相关中枢神经系统病理学的机制数据。