HIV Incidence and Drug Resistance Surveillance using Microdrop HIV Sequencing

使用 Microdrop HIV 测序进行 HIV 发病率和耐药性监测

• 批准号: 10324298
• 负责人: Ha Youn Lee
• 金额: $ 71.21万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-10 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10324298
• 关键词: AIDS prevention; AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Address; Algorithms; Automation; Bioinformatics; Biological Assay; Blood; Centers for Disease Control and Prevention (U.S.); Central Africa; Communities; Complex; Computer software; Consumption; Coupled; Cross-Sectional Studies; Data; Data Analyses; Drug resistance; Epidemic; Evaluation; Genome; Genomics; Geographic Locations; Geography; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; High-Throughput Nucleotide Sequencing; Incidence; Individual; Infection; Intervention; Intervention Trial; Investigation; Laboratories; Length; Link; Minority; Monitor; Movement; Nigeria; Online Systems; Outcome; Output; Parents; Performance; Plasma; Population; Prevalence; Prevention; Prevention trial; Procedures; Publications; Regimen; Reporting; Reproducibility; Research; Research Personnel; Resistance profile; Resolution; Resources; Robot; Robotics; Scheme; Specimen; Standardization; Surveys; System; Techniques; Time; Variant; Viral; Western Africa; antiretroviral therapy; case-based; cloud based; cloud platform; cohort; cost; data hub; design; efficacy evaluation; evidence base; improved; innovation; low and middle-income countries; open source; optimal treatments; pol genes; population survey; programs; real time monitoring; resistance mutation; screening; software as a service; tool; variant detection

The movement of 90-90-90: Treatment for All aims to end the AIDS epidemic by 2030; however, there were still 1.7 million new HIV infections in 2019 worldwide, emphasizing the need to improve current systems of HIV epidemic monitoring and targeted preventions and interventions. As a renewal application of the parent R01 project (AI095066), this proposal builds upon our pioneering accomplishments of inventing microdrop HIV sequencing for high-resolution and low-cost simultaneous HIV incidence and drug resistance surveillance. Our single blood draw assay approach, HIDA (HIV Incidence and Drug Resistance Assay), responds to the growing need to precisely determine HIV incidence and identify drug resistance mutations, including minority variants and cross-class drug resistance mutations linked in a single genome. Our major innovation is to amplify HIV full- length envelope and pol gene sequences within micro-droplets and this compartmental amplification alongside with long-read high-throughput sequencing allows us to extract incidence and drug resistance signatures in a highly precise manner. The central goal of this application is to deliver an end-to-end platform for real-time HIV incidence and drug resistance cross-sectional surveillance. In Aim 1, we propose to conduct a cross-sectional surveillance by accessing 2,658 HIV positive plasma specimens from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), in partnership with Nigeria CDC. By producing massive HIV full-length envelope and pol gene sequences, we will report Nigeria’s regional HIV incidence profiles and 93 WHO surveillance drug resistance mutation prevalence at the population and individual levels. Aim 2 of this application is devoted to devise a low- cost, open-source laboratory automation platform. Recent advances in do-it-yourself automation platforms will facilitate the deployment of HIDA’s microdrop HIV sequencing into low- and middle- income countries for their perpetual HIV surveillance. This standardized, high-throughput automation platform is ideal for performing cross- sectional surveys in resource-limited settings. Aim 3 will integrate HIDA with a cloud-based platform that fully automates incidence and drug resistance surveillance algorithms as a software-as-a-service. The standardization of high-throughput sequencing data analysis is a central requirement for routine surveillance. HIDA’s software- as-a-service will output standardized, high-quality surveillance outcomes directly to users, circumventing the need for investigators to invest in high-cost hardware to perform their own time-consuming analyses. This cloud platform will report both population-level and individual-level incidence and drug resistance profiles in a given geographic region. HIDA via microdrop HIV sequencing will promote global real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool for incidence and drug resistance.

90-90-90运动：治疗所有人的目标是到2030年结束艾滋病流行；然而，仍然有 2019年全球新增艾滋病毒感染者170万人，强调需要改善目前的艾滋病毒防治系统 疫情监测和有针对性的预防和干预。作为父R01的续费申请 项目(AI095066)，这项提议建立在我们发明微滴艾滋病毒的开创性成就的基础上 用于高分辨率和低成本同时监测艾滋病毒发病率和耐药性的测序。我们的 一次抽血分析方法，HIDA(HIV发病率和耐药性分析)，回应了日益增长的 需要准确确定艾滋病毒发病率和识别耐药突变，包括少数变异和 跨类别耐药突变链接在单个基因组中。我们的主要创新是将艾滋病毒完全放大- 微滴内的长度包膜和Pol1基因序列及其隔室扩增 通过长时间阅读的高通量测序，我们可以在 高度精准的态度。该应用程序的中心目标是提供实时HIV的端到端平台 发病率和耐药性横断面监测。在目标1中，我们建议进行横断面 通过获取来自尼日利亚艾滋病毒/艾滋病指标和影响的2658份艾滋病毒阳性血浆样本进行监测 调查(NAIIS)，与尼日利亚疾病控制与预防中心合作。通过产生大量的HIV全长包膜和Poll基因 ，我们将报告尼日利亚的区域艾滋病毒感染概况和93个世卫组织监测的耐药性 在人群和个人层面上的突变流行率。本申请的目标2致力于设计一种低成本- 成本低廉，开源的实验室自动化平台。DIY自动化平台的最新进展将 促进将HIDA的艾滋病毒微滴测序部署到低收入和中等收入国家 对艾滋病病毒进行永久监测。这一标准化、高吞吐量的自动化平台非常适合执行 在资源有限的情况下进行分区调查。AIM 3将HIDA与基于云的平台完全集成 以软件即服务的形式自动执行发病率和耐药性监测算法。标准化 高通量测序数据分析是常规监测的中心要求。日田的软件- 即服务将直接向用户输出标准化、高质量的监控结果，从而规避 调查人员需要投资于高成本的硬件来执行他们自己耗时的分析。这片云 平台将报告给定的人群水平和个人水平的发病率和耐药性概况 地理区域。HIDA通过微滴艾滋病毒测序将促进全球实时监测，作为 一种精确和高通量的发病率和耐药性横断面调查工具。