HIV-1 C Clade Progression and NeuroAIDS

描述(申请人提供)：艾滋病毒-1感染仍然是一个主要的全球公共卫生问题，目前正在东南亚人口稠密的国家蔓延。据报道，拥有10多亿人口的印度有500多万感染者。根据印度政府提供的数据，该国所有邦现在都感染了艾滋病毒-1。在印度，感染HIV-1的分支主要是C分支，而不是西方流行的B分支。艾滋病毒的发展取决于各种因素，包括病毒的种类以及宿主的遗传学。然而，我们对这些关系的了解是对仅与分支B病毒有关的调查的结果。在目前的应用中，我们建议评估宿主基因多态性和HIV辅助受体表达在HIV-1C分支疾病进展中的关系，以及这些因素是如何通过计数CD4细胞和测量病毒载量来影响疾病进展的NP损害的。关于C分支感染的进展及其神经影响的信息对于制定公共卫生干预战略至关重要。因此，我们建议对印度北部昌迪加尔地区居住的200名HIV-1+(C分支)社区男性和女性进行纵向调查。这些人将被调查血浆病毒载量和CD4细胞、CCR5和CXCR4辅助受体的表达；以及CD4细胞上的CCR5基因变异，以及神经认知状况，目的如下：1.(A)：每年测定感染患者的CD4细胞上CCR5和CXCR4的表面表达。1.(B)：利用C分支共受体基因的多态性来确定宿主遗传学对HIV-1 C分支感染进展的影响。2.评估HIV-1+感染者的神经心理损害的患病率和纵向进展。3.研究目标1(A)和目标1(B)的发现与目标2中描述的认知障碍的关系。还将对SES匹配的血清阴性组(N=100)进行年度神经认知评估，以排除由于重复神经心理测试而产生的任何实践影响。研究结果将有助于概括宿主遗传学和辅助受体多态在HIV-1感染的进展和神经认知障碍中的整体作用。

DESCRIPTION (provided by applicant): HIV-1 infection continues to remain a major global public health problem and it is now spreading in the highly populated countries of South East Asia. India, with a population of over 1 billion, has been reported to have over 5 million infected individuals. According to figures available from the Government of India, all states in the country now have HIV-1 infection. The infecting HIV-1 clade in India is mostly clade C rather than clade B which is prevalent in the West. Progression of HIV is dependent upon various factors including the clade of the virus as well as host genetics. However, what we know about these relationships is the result of investigations carried out in relation to only clade B virus. In the present application we propose to assess the relationship between host genetic polymorphism and HIV coreceptor expression on progression of HIV-1 C clade disease and how these factors subsequently affect NP impairment through their effects on disease progression determined by enumerating CD4 cells and measuring the viral load. Information regarding the progression of clade C infection and its neuro-effects is essential in order to make strategies for public health intervention. We therefore propose to investigate longitudinally 200 HIV-1 + (with clade C), community residing men and women in Chandigarh area in North India. These individuals will be investigated for plasma viral loads and CD4 cells and expression of CCR5 and CXCR4 coreceptors; and, CCR5 gene variants on CD4 cells, as well as neurocognitive status with the following aims: 1.(a): To determine annually the surface expression of CCR5 and CXCR4 on CD4 cells of infected individuals. 1 .(b): To determine the impact of host genetics on the progression of HIV-1 clade C infection using polymorphism of clade C co-receptor genes. 2. To evaluate the prevalence and longitudinal progression of neuropsychological impairment among HIV-1 + participants. 3. To investigate the relationships of findings from Aim 1(a) and 1(b) on cognitive impairments delineated in Aim 2. An annual neurocognition evaluation will also be carried out with an SES matched seronegative group (N=100) in order to rule out any practice effects due to repeated neuropsychological testing.The findings will help in generalizing the overall role of host genetics and polymorphism of co-receptors on the progression and neurocognitive deficits occurring in HIV-1 infection.