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

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HIV相关的精神疾病也很常见。也有证据表明，在晚期免疫抑制个体中，HIV亚型D比亚型A与更普遍的神经认知疾病相关。然而，目前还没有针对非洲HIV阳性个体的神经认知或精神状态的大规模人口研究。乌干达的Rakai健康科学项目（RHSP）为开展此类研究提供了独特的机会。RHSP可以从基于人群的队列和HIV临床服务中识别出中度（CD4 350-500）和更严重（CD4 <200）免疫抑制的HIV+个体。Rakai区也是异性恋流行涉及不同艾滋病毒亚型（a、D、重组）的少数地区之一，使我们能够比较亚型对合并症的影响。具体目标是：1.；在基线时，评估与相同Rakai人群中年龄和性别匹配的艾滋病毒成年人相比，接受抗逆转录病毒治疗的20岁、中度免疫抑制（CD4 350-500）和晚期免疫抑制（CD4 < 200）的艾滋病毒阳性成年人是否经历了关键的神经认知/精神共病和功能状态下降（后者将提供乌干达农村尚未获得的规范性数据）。2 .在开始抗逆转录病毒治疗前后，根据HIV亚型和免疫抑制水平，评估HIV+s患者在两年随访期间这些合并症的发展轨迹；定义按HIV亚型分层的痴呆和非痴呆个体脑脊液中区隔化病毒的水平。假设:1。与同一社区的HIV感染者相比，患有中度和晚期免疫抑制的ART阳性HIV感染者在神经认知/精神疾病和功能残疾方面的患病率和严重程度更高，2。抗逆转录病毒治疗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。艾滋病毒阳性患者的神经系统合并症，无论他们是否接受抗逆转录病毒治疗，都会对功能状况产生不利影响，增加健康和社会支持需求。在晚期免疫抑制个体中，HIV亚型D比亚型A与痴呆风险增加相关，5。脑脊液中更大的病毒遗传区隔化与痴呆相关，并且与a型相比，D亚型增加。该研究将为与神经认知/精神合并症相关的预防和支持计划的发展提供流行病学和临床数据，以及艾滋病毒相关中枢神经系统病理的机制数据。

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.