A Simple, Sensitive and Accurate HIV-1 Viral Load Test

简单、灵敏且准确的 HIV-1 病毒载量测试

• 批准号: 6746632
• 负责人: XING-XIANG LI
• 金额: $ 29.97万
• 依托单位: CELLEX, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746632
• 关键词: AIDS; AIDS /HIV diagnosis; HIV infections; bioassay; biomarker; biomedical equipment development; clinical biomedical equipment; clinical research; diagnosis design /evaluation; diagnosis quality /standard; drug screening /evaluation; human immunodeficiency virus 1; human tissue; pathologic process; patient monitoring device; portable biomedical equipment; virus RNA; virus load

DESCRIPTION (provided by applicant): Monitoring HIV viral load, or the concentration of viral RNA in the plasma, is part of the standard care of HIV-infected individuals. Since HIV viral load is indicative of current virologic status, it is used as a marker for disease progression and anti-retroviral drug therapy efficacy. Two critical decisions in HIV/AIDS patient care are primarily based on HIV viral load measurements: when to initiate drug therapy and when to switch or adjust drug therapy regimen, as recommended in the "Guidelines for the use of Antiretroviral Agents in HIV-infected Adults and Adolescents". Although three HIV-1 viral load tests are commercially available in US, they are all complicated to operate and expensive to use. More importantly, these tests are inaccurate with coefficient of variation (CV) up to 100%. The poor performance characteristics for these tests reflect the limitation of the technologies, which involve multiple cycles of amplification steps to amplify the target (HIV-1 RNA) or signal in order to improve the sensitivity. The complex and expensive nature of these tests also limits their use mostly to the developed countries; few HIV infected patients in developing countries have access to viral load testing even if they have access to charitable sources of anti-retroviral drugs. We propose here to use our microparticle based amplification (MBA) technology to develop a simple, sensitive and accurate HIV-1 viral load test. Specifically, we will validate the MBA-based assay in terms of its (a) simplicity--three steps with total assay time of < 2.0 hours and labor time < 30 minutes; (b) sensitivity--better than 100 HIV-1 RNA copies, (c) accuracy--a coefficient of variation of < 50%, and (d) comparability with a FDA approved test--correlation of coefficient (R 2) >_0.9. A successful outcome of this Phase I study will lead to a Phase II study, during which we will demonstrate the assay performance in ctinical settings by testing large numbers of clinical samples. The successful outcome of Phase II study will lead to the commercialization of the test, which will give users a less expensive and more accurate alternative for HIV-1 viral load test.

描述（由申请人提供）：监测HIV病毒载荷或血浆中病毒RNA的浓度，是HIV感染者的标准护理的一部分。由于HIV病毒载量指示当前的病毒状况，因此它用作疾病进展和抗报告药物治疗疗效的标志。艾滋病毒/艾滋病患者护理中的两个关键决定主要基于艾滋病毒病毒负荷测量：何时开始药物治疗以及何时转化或调整药物治疗方案，如“在HIV感染的成年人和青少年使用抗逆转录病毒药物的指南”中的建议。 尽管我们在我们的商业上可以使用三个HIV-1病毒负荷测试，但它们的操作都很复杂且使用昂贵。更重要的是，这些测试不准确，变异系数（CV）高达100％。这些测试的性能特征差反映了技术的局限性，该技术涉及放大步骤的多个循环以扩增目标（HIV-1 RNA）或信号以提高灵敏度。这些测试的复杂和昂贵的性质也限制了它们主要用于发达国家；在发展中国家，很少有艾滋病毒感染的患者可以使用病毒负荷测试，即使他们可以使用抗逆转录病毒药物的慈善来源。 我们在这里建议使用基于微粒的扩增（MBA）技术来开发简单，敏感和准确的HIV-1病毒负载测试。具体而言，我们将根据其（a）简单性来验证基于MBA的测定法 - 总测定时间<2.0小时，劳动时间<30分钟； （b）灵敏度 - 比100 HIV-1 RNA拷贝，（c）精度 - 变异系数<50％，以及（d）与FDA批准的测试的可比性 - 系数（r 2）> _0.9。 这一I阶段研究的成功结果将导致II期研究，在此期间，我们将通过测试大量临床样本来证明在CTinical设置中的测定性能。第二阶段研究的成功结果将导致测试的商业化，这将为用户提供更便宜，更准确的HIV-1病毒负载测试替代方案。