Combined phylogenetic and epidemiological analysis to identify HIV transmission sources in Seattle WA

结合系统发育和流行病学分析来确定华盛顿州西雅图的艾滋病毒传播源

• 批准号: 9305837
• 负责人: Joshua T Herbeck
• 金额: $ 49.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9305837
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Adolescent; Affect; Africa South of the Sahara; African; Age; American; Automobile Driving; Behavioral; Big Data; Caring; Clinical; Clinical Data; Clinical Research; Collaborations; Communities; Continuity of Patient Care; County; Data; Data Set; Data Sources; Databases; Decentralization; Diagnosis; Education and Outreach; Epidemic; Epidemiology; Ethnic Origin; Generations; Genotype; Goals; Government; Guide prevention; HIV; HIV Infections; HIV diagnosis; HIV-1; Health Resources; Heterosexuals; Hispanics; Human immunodeficiency virus test; Incidence; Individual; Infection; Information Systems; Interview; Latin America; Latino; Link; Location; London; Methodology; Modeling; Molecular; Molecular Epidemiology; Netherlands; Newly Diagnosed; Patients; Pattern; Pediatric Hospitals; Persons; Phylogenetic Analysis; Play; Population; Prevention; Primary Infection; Process; Public Health; Risk; Risk Factors; Role; Services; Sexual Partners; Source; Subgroup; Suggestion; System; Testing; United States; Universities; Washington; adolescent men who have sex with men; behavioral study; cohort; college; epidemiologic data; epidemiology study; expectation; experience; genetic analysis; genetic linkage analysis; high risk; innovation; men who have sex with men; methamphetamine use; novel; novel strategies; pre-exposure prophylaxis; research and development; sex; success; surveillance data; trait; transmission process; young men who have sex with men

ABSTRACT Despite substantial progress in education, outreach, diagnosis, ART and PrEP use, HIV incidence among MSM in the U.S. has not decreased substantially in the last decade, with increases in new infections seen in younger MSM. There is an urgent need for novel approaches to identify the main sources of ongoing transmission. Our project leverages the existence of multiple, decentralized, HIV databases in Seattle that contain HIV pol genotypes from, in total, >4,000 individuals (>50% of the HIV-infected population), each linked to a range of behavioral, clinical, and epidemiological data (the databases are from Public Health–Seattle and King County, PHSKC; University of Washington HIV Information System, UWHIS; UW Primary Infection Cohort, PIC; and Seattle Children’s Hospital, SCH). From these databases, we will create a single, combined pol dataset, which will facilitate novel molecular epidemiological analyses with diverse HIV data types. Our creation of this combined dataset (via processes of de-identification, anonymization, record linkage and genetic analysis) will serve as a model for communities that have comparable decentralized HIV data sources and available HIV genotypes. Subsequently, we will use this dataset for innovative “second generation” phylogenetic studies. First, we will describe HIV transmission patterns among key affected populations, including foreign-born Seattle residents and adolescent MSM. We hypothesize that phylogenetic linkage analyses will indicate that more than 80% of African- born cases, but less than 50% of Latino cases, are imported, with important public health implications. We also hypothesize that phylogenetic analysis of our combined dataset will reveal that adolescent MSM are frequently found in clusters with older MSM, at rates elevated above baseline expectations, indicating that age-discrepant pairs may play a role in driving transmission in this population in Seattle. Second, we will, in collaboration with Christophe Fraser and Oliver Ratmann (Imperial College London), estimate the proportion of transmissions in Seattle arising from each stage of the infection and care continuum. For this cutting edge analysis of the Seattle dataset, we will extend a data-driven clinical and phylogenetic methodology that was originally used to study MSM transmission in the Netherlands. We hypothesize that >50% of transmissions in Seattle arise from undiagnosed individuals, while transmission from patients not retained in care is less than previously estimated. Seattle is an ideal location to perform this project, as even with abundant public health resources, active and strong collaborations between academic and governmental communities, and great successes in the HIV care cascade, the epidemic persists.

抽象的 尽管在教育，外展，诊断，艺术和准备使用方面取得了长足进展，但MSM中的HIV事件发生了 在过去的十年中，美国没有大幅下降，随着年轻感染的新感染增加 MSM。迫切需要采用新颖的方法来识别正在进行的传播的主要来源。我们的 项目利用西雅图的多个，分散的HIV数据库的存在 来自> 4,000个个体（>感染HIV的人群的50％）的基因型，每种 行为，临床和流行病学数据（数据库来自公共卫生 - 座位和金县， phskc;华盛顿大学艾滋病毒信息系统，UWHIS； UW原发性感染队列，图片；和 西雅图儿童医院，Sch）。从这些数据库中，我们将创建一个单个组合的POL数据集，该数据集 将促进使用潜水HIV数据类型的新分子流行病学分析。我们创建了这个结合的 数据集（通过去识别，匿名，记录联系和遗传分析的过程）将作为一个 具有可比较的分散HIV数据来源和可用HIV基因型的社区模型。 随后，我们将使用此数据集进行创新的“第二代”系统发育研究。首先，我们会的 描述关键受影响人群的艾滋病毒传播模式，包括外国出生的西雅图居民和 青少年MSM。我们假设系统发育连锁分析将表明超过80％的非洲 - 出生的病例，但不到50％的拉丁裔案件被进口，具有重要的公共卫生影响。我们也是 假设我们组合数据集的系统发育分析将表明青少年MSM经常是 在具有较旧MSM的群集中发现，以高于基线期望的速度提高，表明年龄段的人 对在西雅图的这一人群中推动传播方面可能发挥作用。第二，我们将与 克里斯托夫·弗雷泽（Christophe Fraser）和奥利弗·拉特曼（Oliver Ratmann）（伦敦帝国学院），估计了传播的比例 西雅图来自感染和护理连续体的每个阶段。对于西雅图的尖端分析 数据集，我们将延长一种数据驱动的临床和系统发育方法，该方法最初用于研究 荷兰的MSM传输。我们假设西雅图的50％的传输来自 未诊断的个体，而未保留护理的患者的传播却小于先前估计的。 西雅图是执行该项目的理想场所，即使拥有大量的公共卫生资源， 学术和政府社区之间的强大合作，以及艾滋病毒护理方面的巨大成功 级联，流行病仍然存在。