HIV-1 C Clade Progression and NeuroAIDS

描述（由申请人提供）：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众多的国家蔓延。据报道，人口超过10亿的印度有500多万感染者。根据印度政府提供的数字，该国所有邦现在都有艾滋病毒-1感染。在印度，感染HIV-1的分支主要是C分支，而不是在西方流行的B分支。艾滋病毒的进展取决于各种因素，包括病毒的进化支以及宿主遗传。然而，我们对这些关系的了解是仅对B支病毒进行调查的结果。在目前的应用中，我们建议评估宿主遗传多态性和HIV共受体表达在HIV- 1c进化支疾病进展中的关系，以及这些因素如何通过计数CD4细胞和测量病毒载量来确定它们对疾病进展的影响，从而影响NP损伤。有关C支感染进展及其神经效应的信息对于制定公共卫生干预策略至关重要。因此，我们建议纵向调查印度北部昌迪加尔地区200名HIV-1 +（进化支C），居住在社区的男性和女性。将对这些个体进行血浆病毒载量和CD4细胞以及CCR5和CXCR4辅助受体表达的研究；CD4细胞的CCR5基因变异，以及神经认知状态，目的如下：1。(a)：每年测定感染者CD4细胞表面CCR5和CXCR4的表达。1 ．(b)：利用进化枝C共受体基因多态性确定宿主遗传学对HIV-1进化枝C感染进展的影响。2. 评估HIV-1 +参与者中神经心理障碍的患病率和纵向进展。3. 研究目的1(a)和1(b)的发现与目的2所描述的认知障碍之间的关系。每年还将对SES匹配的血清阴性组（N=100）进行神经认知评估，以排除重复神经心理测试造成的任何练习影响。这些发现将有助于概括宿主遗传学和共受体多态性在HIV-1感染的进展和神经认知缺陷中的总体作用。

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.