VIRUS ISOLATE-BASED HIV-1 RESISTANCE ASSAY

描述：(改编自申请者摘要)所有FDA批准 抗逆转录病毒药物未能完全抑制病毒复制。结果 持续的病毒复制和基因突变，耐药病毒 出现并导致药物失效和疾病进展。没有标准 临床耐药监测试验，启动或终止的决定 切换抗逆转录病毒治疗方案是复杂的。这样的测试具有 有可能成为管理艾滋病毒疾病的关键工具。 近年来，新一代表型耐药检测方法不断发展。 与传统的基于PBMC的方法相比具有几个优点。申请者 已经开发出一种基于初级病毒分离(PVI)的检测方法，它可能具有独特的 优势。首先，PVI检测对不同的原代细胞高度敏感 HIV-1的分离；第二，它能够分析整个病毒种群 无需选择；第三，它可以检测不同药物的次要种类 病毒群体中的抗药性病毒；第四，来自单一原始病毒 病毒存量它可以评估影响任何水平的药物的敏感性 病毒复制周期；它具有高吞吐量能力，并且可以 定量测定对多种药物的敏感性和耐药性 同时。在这个第一阶段应用中，他们建议定义和 使PVI检测的条件标准化，以 准确、重复性地检测表型耐药特性 主要的HIV-1病毒分离株。为了实现这一目标，他们的具体目标是： (1)将PVI检测与遗传和表型面板进行比较 定义耐药病毒和临床样本；(2)定义实验 优化PVI检测性能的参数；并定义 优化PVI检测性能的实验参数；以及(3) 开发一种分析HIV-1耐药性的单一实验方法 对抗针对病毒生命周期中任何步骤的药物。 建议的商业应用：不可用

DESCRIPTION: (Adapted from Applicant's Abstract) All FDA approved antiretroviral drugs fail to completely suppress virus replication. As a result of persistent virus replication and genetic mutation, drug resistance viruses emerge and lead to drug failure and disease progression. Without a standard clinical drug resistance monitoring test, the decision for initiating or switching antiretroviral treatment regimens is complicated. Such a test has the potential to become a critical tool for the management of HIV disease. Recently, new generation phenotypic drug resistance assays have been developed with several advantages over conventional PBMC-based methods. The applicants have developed a primary virus isolate- (PVI) based assay that may have unique advantages. First, the PVI assay is highly sensitive to diverse primary isolates of HIV-1; second, it is able to analyze the entire viral population without selection; third, it can detect minor species of different drug resistant viruses within a virus population; fourth, from a single original virus stock it can evaluate the susceptibility of drugs that effect any level of the virus replication cycle; it has high throughput capability and can quantitatively measure sensitivity and resistance to multiple drugs simultaneously. In this phase I application, they propose to define and standardize the conditions under which the PVI assay can be performed to accurately and reproducibly measure the phenotypic drug resistance properties of primary HIV-1 virus isolates. To accomplish this their specific aims are: (1) to compare the PVI assay against panels of genetically and phenotypically defined resistant viruses, and clinical samples; (2) to define the experimental parameters that optimize the performance of the PVI assay; and define the experimental parameters of the PVI assay that optimize its performance; and (3) to develop a single experimental approach for analyzing HIV-1 resistance against drugs that target any step in the virus life cycle. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE