CORE--ADVANCED TECHNOLOGY LABORATORIES

核心--先进技术实验室

• 批准号: 5205118
• 负责人: CHARLES VAN DER HORST
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5205118
• 关键词: AIDS; AIDS therapy; HIV infections; antiAIDS agent; antibody neutralization test; biomarker; biomedical facility; clinical research; cooperative study; cytokine; drug metabolism; human immunodeficiency virus 1; human subject; human therapy evaluation; immunity; immunology; neutralizing antibody; pathologic process; pharmacokinetics; pharmacology; polymerase chain reaction; serology /serodiagnosis; virus antigen

The virologic markers that to date have been used as secondary endpoints in most of The ACTG protocols have been shown to be inadequate. Newer techniques that are more quantitative, faster, and less expensive are necessary. Most importantly, these new markers should change with disease progression or with effective drug therapy. More rapid assays for the determination of drug sensitivity are also needed immediately as increasing numbers of patients stay on medication for prolonged periods of time. All of these assays should correlate with the clinical data obtained from the patient. Previous work in this laboratory has indicated that virtually all of the infectious HIV found in cell-free plasma is in the form of immune complexes. Infectious immune complexes are easily and efficiently precipitated from plasma with polyethylene glycol. Procedures taking advantage of these features will be developed that will: (1) improve the p24 antigen assay and make it more clinically relevant and (2) streamline drug sensitivity testing by directly screening plasma for sensitive or resistant isolates. This assay will help the clinician determine the best drug to use for a particular patient in a more appropriate amount of time (1 to 2 weeks). In addition to the development of new virologic markers the laboratory will continue to provide the required virologic support of the ACTG by performing quantitative HIV cell and plasma cultures and p24 antigen assays. The lab will also continue to participate in the development of a consensus protocol for the isolation of drug resistant isolates from cells and the determination of their clinical relevance. The long term goal of the laboratory is to investigate the role of infectious immune complexes in the natural history and pathogenesis of HIV infection.

迄今为止，病毒学标志物已被用作次要终点， 大多数ACTG协议已被证明是不充分的。 较新 更定量、更快、更便宜的技术， 必要 最重要的是，这些新的标记物应该随着疾病而变化。 进展或有效的药物治疗。 更快速的检测 随着药物敏感性的增加， 许多病人长期服药。 所有 这些测定的结果应与从临床试验中获得的临床数据相关。 病人 这个实验室以前的工作表明，几乎所有的 在无细胞血浆中发现的传染性HIV是以免疫形式存在的。 配合物 感染性免疫复合物很容易有效地 用聚乙二醇从血浆中沉淀。 采取的程序 将开发这些功能的优势，这将：（1）提高 p24抗原检测，使其更具有临床相关性;（2）简化 通过直接筛选血浆中敏感或 耐药菌株 该分析将帮助临床医生确定最佳的 在更适当的时间内用于特定患者的药物 （1至2周）。 除了开发新的病毒学标志物外，实验室还将 继续为ACTG提供所需的病毒学支持， 进行定量HIV细胞和血浆培养以及p24抗原 分析。 实验室还将继续参与开发 从细胞中分离耐药分离株的共识方案 并确定其临床相关性。 实验室的长期目标是研究 感染性免疫复合物在HIV自然史和发病机制中的作用 感染