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

描述(申请人提供)：HIV相关神经认知障碍(Hand)是美国HIV的一种常见神经并发症，我们的初步数据表明，乌干达31%的HIV+患者可能患有HIV痴呆，这是Hand最严重的阶段。与艾滋病毒相关的精神病发病率也很常见。也有证据表明，在患有晚期免疫抑制的个体中，D亚型HIV与比A亚型更普遍的神经认知疾病有关。然而，目前还没有关于艾滋病病毒携带者的神经认知或精神状态的大规模人群研究。乌干达的Rakai健康科学计划(RHSP)为开展此类研究提供了独特的机会。RHSP可以从其基于人群的队列和艾滋病毒临床服务中识别中度(CD4350-500)和较严重(CD4HSP200)免疫抑制的艾滋病毒+个体。Rakai区也是少数几个异性流行涉及不同HIV亚型(A、D、重组体)的地区之一，使我们能够比较亚型对共病的影响。具体目标是：1.在基线，评估年龄20岁、中度免疫抑制(CD4350-500)和晚期免疫抑制(CD4Rakai 200)的幼稚艾滋病毒+成年人与同一≥人群中年龄和性别匹配的艾滋病毒-成年人相比，是否经历了关键的神经认知/精神并存和功能状态下降(后者将提供乌干达农村地区尚未获得的规范数据)，2.评估艾滋病毒+S在抗逆转录病毒疗法启动前后对艾滋病毒亚型和免疫抑制水平进行两年随访时这些共病的轨迹，3.根据HIV亚型对痴呆患者和非痴呆患者的脑脊液中的病毒水平进行分析。假设：1.与同一社区中的艾滋病毒携带者相比，患有中度和重度免疫抑制的幼稚HIV+患者的神经认知/精神疾病和功能残疾的患病率和严重程度更高；2.抗逆转录病毒治疗将降低共病的患病率和严重程度，但发病率仍将显著高于艾滋病毒携带者；3.HIV+患者的神经并存，无论他们是否服用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.在患有严重免疫抑制的个人中，艾滋病毒D亚型与A亚型相比，痴呆的风险更大，5.脑脊液中更大的病毒遗传区隔与痴呆症相关，与A亚型相比，D亚型的病毒遗传区隔作用更强。这项研究将为制定与神经认知/精神共病有关的预防和支持计划提供流行病学和临床数据，并提供与艾滋病毒相关的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 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.