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.

迄今已被用作次要终点的病毒学标记 大多数ACTG协议已被证明不足。 较新 更定量，更快且价格较低的技术是 必要的。 最重要的是，这些新标记应随着疾病而改变 进展或有效的药物治疗。 更快的测定 随着增加的增加，还需要确定药物敏感性 长时间服用药物的患者人数。 全部 这些测定应与从 病人。 该实验室的先前工作表明，几乎所有 在无细胞等离子体中发现的感染性HIV是免疫的形式 复合物。 感染性免疫复合物很容易有效 用聚乙烯乙二醇从血浆沉淀。 程序采用 将开发这些功能的优势，该功能将：（1）改进 p24抗原测定法，使其在临床上更相关，并且（2）简化 药物敏感性测试通过直接筛选血浆敏感或 抗性分离株。 该测定法将帮助临床医生确定最好的 在更合适的时间内用于特定患者的药物 （1至2周）。 除了开发新的病毒标记，实验室还将 继续提供ACTG的所需病毒学支持 进行定量的HIV细胞和血浆培养物以及P24抗原 测定。 实验室还将继续参与 从细胞中分离耐药性分离株的共识方案 并确定其临床相关性。 实验室的长期目标是调查 艾滋病毒的自然病史和发病机理中的传染性免疫复合物 感染。