Measuring the Latent Reservoir and Monitoring Eradication Strategies

测量潜在储库并监测根除策略

• 批准号: 8326895
• 负责人: DOUGLAS D RICHMAN
• 金额: $ 40.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326895
• 关键词: Address; Animal Model; Anti-Retroviral Agents; Biological Assay; Blood; Blood Volume; CD4 Positive T Lymphocytes; Cells; Characteristics; Clinical; DNA; Detection; Development; Flow Cytometry; HIV; HIV Infections; HIV-1; Human; In Vitro; Infection; Instruction; Intervention; Investigation; Latent Virus; Macaca; Measurement; Measures; Methods; Microfluidics; Modeling; Monitor; Natural History; Patients; Research Personnel; Research Project Grants; SIV; Sampling; Specimen; Study Subject; Technology; Testing; Tissues; Viral; Virus; antiretroviral therapy; collaboratory; improved; in vitro Model; in vivo; innovation; macrophage; monocyte; peripheral blood; programs; purge; simian human immunodeficiency virus; treatment effect; viral DNA

PROJECT SUMMARY (See instructions): The assays that have been applied to measure the latent reservoir in studies performed to date have been imprecise, in some cases non-specific, and in all cases near the threshold of detection for specimens obtained from subjects effectively treated with antiretroviral therapy. A successful Collaboratory effort to eradicate the latent reservoir must have assays available that can reliably quantify this reservoir and measure reductions in its size. In Project 4.1, superior assays in development for integrated viral DNA and for viral infectivity will be refined and validated for HIV, and then applied to both the SIV and RT-SHIV macaque models. They will then be applied to in vitro models of latency and to cells and tissues obtained from infected macaques and HIV-infected study subjects, as part of other Collaboratory research projects. Microfluidic applications to these assays will address the question of the representativeness of the proviral reservoir for replication-competent virus and try to explain some of the mechanisms for replication in competent virus. The presence of HIV DNA and infectivity in blood macrophages, as a potential reservoir, will also be examined. These studies to improve measurements of the latent reservoir and interventions to purge it will involve close interactions and the exchange of methods and materials with several of the project and core Collaboratory investigators.

项目摘要（请参阅说明）： 在迄今为止所进行的研究中，已应用用于测量潜在储层的测定是不精确的，在某些情况下是非特异性的，并且在所有情况下，从有效地接受抗逆转录病毒疗法治疗的受试者获得的标本的检测阈值附近。一项成功的合作努力来消除潜在储层必须有可靠地量化此储层和的测定法 测量其大小的减少。在项目4.1中，将对HIV进行完善并验证综合病毒DNA和病毒感染性的开发测定法，然后应用于SIV和RT-SHIV猕猴模型。然后，它们将应用于潜伏期的体外模型，以及从感染的猕猴和感染HIV感染的研究对象获得的细胞和组织，作为其他协作研究项目的一部分。 这些测定法上的微流体应用将解决前病毒储层对复制能力病毒的代表性的问题，并试图解释某些在有能力的病毒中复制的机制。还将检查HIV DNA和血液巨噬细胞中的感染性，作为潜在储层。这些研究旨在提高对潜在储层的测量以及清除干预措施，将涉及与几个项目和核心协作研究人员的方法和材料进行密切相互作用以及方法和材料的交换。