HIV-1 C Clade Progression and NeuroAIDS

描述（由申请人提供）：HIV-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。印度人口超过10亿，据报有500多万感染者。根据印度政府提供的数字，目前印度所有邦都有艾滋病毒1型感染病例。在印度感染HIV-1的进化枝主要是C进化枝，而不是西方流行的B进化枝。HIV的进展取决于各种因素，包括病毒的进化枝以及宿主遗传学。然而，我们对这些关系的了解是仅对进化枝B病毒进行调查的结果。在本申请中，我们提出评估宿主遗传多态性和HIV辅助受体表达对HIV-1 C进化枝疾病进展的关系，以及这些因素如何随后通过它们对疾病进展的影响来影响NP损伤，所述疾病进展通过计数CD 4细胞和测量病毒载量来确定。关于C支感染的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200 HIV-1 +（C支），社区居住在印度北部的昌迪加尔地区的男性和女性。将对这些个体的血浆病毒载量和CD 4细胞以及CCR 5和CXCR 4辅助受体的表达进行研究;以及CD 4细胞上的CCR 5基因变体，以及神经认知状态，目的如下：1. (a)每年检测感染者CD 4细胞表面CCR 5和CXCR 4的表达。1 .一、(b)目的：利用C支辅助受体基因多态性，确定宿主遗传学对HIV-1 C支感染进展的影响。2.评估HIV-1 +参与者中神经心理损害的患病率和纵向进展。3.研究目标1（a）和1（B）的结果与目标2中描述的认知障碍之间的关系。每年的神经认知评估也将进行与SES匹配的血清阴性组（N=100），以排除任何实践的影响，由于重复neuropsychological testing.The研究结果将有助于概括宿主遗传学和多态性的共受体的进展和神经认知缺陷发生在HIV-1感染的整体作用。

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.