Immune Activation in Virologically Suppressed Indian HIV-infected Patients

病毒学受到抑制的印度艾滋病毒感染者的免疫激活

• 批准号: 8728729
• 负责人: Savita Pahwa
• 金额: $ 21.36万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728729
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Anti-Retroviral Agents; Automobile Driving; Benchmarking; Biological Assay; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Cell Count; Cells; Cellular translocation; Clinical; Comorbidity; Cross-Sectional Studies; DNA; Data; Detection; Diabetes Mellitus; Disease; Disease Attributes; Education; Epidemic; Epithelium; Event; Failure; Future; Genetic Predisposition to Disease; Guidelines; HIV; HIV Infections; HIV Seropositivity; Immune; Immunology; Immunophenotyping; Impaired cognition; India; Infection; Inflammation; Inflammatory; Interruption; Life; Link; Lipopolysaccharides; Longevity; Malignant Neoplasms; Measures; Organ; Osteoporosis; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Phenotype; Plasma; Population; Recovery; Research; Research Personnel; Residual state; Rest; Risk; Sampling; Source; Staging; Testing; Universities; Viral; Viral load measurement; Viremia; Virus; Virus Replication; antiretroviral therapy; cohort; cytokine; falls; immune activation; in vivo; memory CD4 T lymphocyte; microbial; novel; premature; prevent; public health relevance; reconstitution; repository; treatment center; trend; virology

DESCRIPTION (provided by applicant): With potent new combination antiretroviral therapies (cART), the life-span of HIV-infected persons has been steadily increasing, but is often complicated by premature onset of non-AIDS co-morbidities such as cardiovascular disease (CVD), attributed to persistence of immune activation (IA) despite suppression of plasma virus to undetectable levels. One mechanism of persistent IA is gut microbial translocation (MT) resulting from HIV-associated gut damage early in HIV infection, but why the gut recovery is delayed is unclear. While it is known that HIV establishes reservoirs early in infection necessitating life-long uninterrupted therapy to prevent virus rebound, our studies suggest that LLVR is in fact occurring despite plasma virus suppression and that it is associated with IA. Whether the virus reservoir per se is driving immune activation directly or indirectly is unknown. We are proposing a partnership between investigators in YRGCARE in Chennai, India and University of Miami, in Miami USA to examine a novel hypothesis that patients on cART with suppressed plasma viremia continue to have persistent low level virus replication that drives immune activation and gut damage. Further we hypothesize that lower nadir CD4 is associated with greater virus reservoir size, immune activation, co-morbidity and poorer immune reconstitution. Aim 1 will determine the size of virus reservoir and level of residual viral replication in CD4 T cells of patients on suppressive ART; total and unintegrated HIV DNA will be quantified and CD4 T cells evaluated for HIV induction ex-vivo. In aim 2, level of immune activation will be assessed by plasma measures of inflammatory cytokines, endothelial activation markers, MT, and cellular phenotyping. In aim 3, the impact of nadir CD4 on virus reservoirs, immune activation, immune reconstitution and evidence of CVD will be investigated. For these aims, a cross-sectional study in patients on cART for>48 weeks, plasma VL<40 copies with varying nadir CD4 counts will be conducted. This study will establish novel state of the art immunology and virology assays at YRGCARE, provide preliminary data of global relevance and prepare us for future collaborative research, including studies aimed at eradicating reservoirs and curing HIV/AIDS.

描述（由申请人提供）：通过有效的新组合抗逆转录病毒疗法（CART），HI​​V感染者的寿命一直在稳步增长，但由于非辅助性诸如心血管疾病（CVD）等非AID的过早发作，但由于免疫激活的持续性（ia cot prosection），通常会因心血管疾病（CVD）等非AID的过早发作而变得复杂。持续性IA的一种机制是肠道微生物易位（MT）是由HIV相关的HIV感染引起的，但尚不清楚为什么肠道恢复延迟。尽管众所周知，艾滋病毒在感染的早期建立了水库，需要终身不间断的治疗以防止病毒反弹，但我们的研究表明，尽管血浆病毒抑制了，但实际上是LLVR发生的，并且与IA有关。病毒储层本身是直接还是间接驱动免疫激活。我们提议在印度钦奈的YRGCARE和美国迈阿密大学的YRGCARE之间建立合作伙伴关系，以研究一种新的假设，即患有抑制血浆病毒血症的货车的患者继续具有持久的低水平病毒复制，从而驱动免疫激活和肠道损害。此外，我们假设较低的Nadir CD4与较大的病毒储层大小，免疫激活，合并症和免疫重建较差有关。 AIM 1将确定病毒储量的大小和抑制性ART患者CD4 T细胞中残留病毒复制水平；将对HIV的总HIV DNA和未整合的HIV DNA进行定量，并评估了用于HIV诱导的EX-VIVO的CD4 T细胞。在AIM 2中，免疫激活水平将通过血浆炎症细胞因子，内皮活化标记，MT和细胞表型的血浆测量评估。在AIM 3中，将研究NADIR CD4对病毒储量，免疫激活，免疫重建和CVD证据的影响。对于这些目的，将对卡车上的患者进行横断面研究，持续48周，将进行等离子VL <40副本，其Nadir CD4数量有所不同。这项研究将在YRGCARE建立新颖的先进免疫学和病毒学测定状态，提供全球相关性的初步数据，并为我们做准备未来的合作研究，包括旨在消除储层和治疗HIV/AIDS的研究。