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（由适用提供）：与HIV相关的神经认知障碍（HARD）是美国HIV的常见神经系统并发症，我们的初步数据表明，乌干达的31％的HIV+个体可能患有HIV痴呆症，这是最严重的手。与艾滋病毒相关的精神病性多发性也很常见。也有证据表明，在具有晚期免疫抑制的个体中，HIV亚型D与亚型A相比更普遍的神经认知发病率有关。但是，没有关于艾滋病毒+非洲个体神经认知或精神病状态的基于人群的大量研究。乌干达的Rakai Health Sciences计划（RHSP）为进行此类研究提供了独特的机会。 RHSP可以从其基于人群的同伙和HIV诊所服务中鉴定出具有中度（CD4 350-500）和更严重（CD4 <200）的HIV+个体（CD4 <200）。 Rakai地区也是异性恋流行病涉及不同的HIV亚型（A，D，重组者）的少数地区之一，使我们能够比较亚型对合并症的影响。具体目的是：1。在基线时，评估年龄衰老的成年人是否具有适度的免疫抑制（CD4 350-500），并且先进的免疫抑制（CD4 <200）经验关键的神经认知/精神病学/精神病学/精神病学经验，并与成人相同的人数匹配（与性别相比），该范围与正常的数据相比，该状态（与性别相比，均与性格相同）（与性别相比，均与性别相匹配（范围）（均为性别相比）（均为性格率）（均与性别相匹配（等级）（当时的性别范围）（均可提供的范围（均可提供）。在乌干达的粗糙中，尚未获得），2。在HIV亚型的两年内评估HIV+s中这些共生率的轨迹和在艺术开始之前和之后的免疫抑制水平，以及第3个。定义了由HIV Subsepepe的患者的CSF水平，以定义分型病毒的水平。假设：1。具有中度和晚期免疫抑制的Art nana¿ve HIV+个体具有更高的神经认知/精神病/精神病性发病率和功能性残疾的严重性和严重程度，与同一社区中的HIV人相比，与同一社区相比，ART将降低与HIV的人相比，ART将降低HIV的率高于HIV，而HIV率则更高。 4. HIV亚型D与痴呆症患者相比，与亚型的痴呆症患者相比，与亚型相比，与dementia contia corptial corpe and A. Typer a。与神经认知 /精神病合并症有关的预防和支持计划以及与HIV相关的CNS病理学的机理数据。