HIV-1 C Clade Progression and NeuroAIDS

HIV-1 C 进化枝进展与神经艾滋病

• 批准号: 7168348
• 负责人: MAHENDRA KUMAR
• 金额: $ 50.08万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-29 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168348
• 关键词: India; clinical research; genes; genetics; infection; receptor

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.

描述（由申请人提供）：HIV-1感染仍然是全球主要的公共卫生问题，现在正在东南亚人口稠密的国家中传播。据报道，印度人口超过10亿，有超过500万感染者。根据印度政府可获得的数据，该国所有州现在都有HIV-1感染。印度的感染HIV-1进化枝主要是进化枝C，而不是在西方普遍存在的进化枝B。 HIV的进展取决于各种因素，包括病毒的进化枝和宿主遗传学。但是，我们对这些关系的了解是仅针对进化枝B病毒进行的调查的结果。在本应用中，我们建议评估宿主遗传多态性与HIV共受体表达与HIV-1 C进化疾病进展的关系，以及这些因素随后如何通过枚举CD4细胞和测量病毒性来确定的疾病进展的影响来影响NP损害加载。有关进化枝C感染及其神经效应的进展的信息对于制定公共卫生干预策略至关重要。因此，我们建议调查纵向200 HIV-1 +（与进化枝C），在印度北部昌迪加尔地区居住的社区。这些个体将接受血浆病毒载荷和CD4细胞的研究，以及CCR5和CXCR4共肽的表达。并且，CCR5基因在CD4细胞上的变体以及以下目的的神经认知状态：1。（a）：在感染个体的CD4细胞上每年确定CCR5和CXCR4的表面表达。 1。（b）：确定使用进化枝C共受体基因的多态性的宿主遗传学对HIV-1进化枝C感染进展的影响。 2。评估HIV-1 +参与者中神经心理学障碍的患病率和纵向进展。 3。为了调查目标1（a）和1（b）在AIM 2中描述的认知障碍的发现的关系。还将使用SES匹配的血清神经群（n = 100）进行年度神经认知评估，以便排除由于反复的神经心理学测试而引起的任何实践效应。该发现将有助于概括宿主遗传学的总体作用以及共受体对HIV-1感染中发生的进展和神经认知缺陷的总体作用。