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

摘要 尽管在教育、外展、诊断、抗逆转录病毒疗法和预防接种计划的使用方面取得了实质性进展，但男男性接触者中艾滋病毒的发病率 在过去的十年里，美国的新感染人数并没有大幅下降，新感染人数在年轻人群中出现了增加 MSM。迫切需要新的方法来确定持续传播的主要来源。我们的 该项目利用西雅图现有的多个分散的艾滋病毒数据库，这些数据库包含艾滋病毒Poll 总共有4,000个人(占艾滋病毒感染人口的50%)的基因类型，每个基因类型都与一系列 行为、临床和流行病学数据(数据库来自公共卫生-西雅图和金县， 华盛顿大学艾滋病毒信息系统；华盛顿大学初级感染队列；以及 西雅图儿童医院，SCH)。从这些数据库中，我们将创建单个组合POL数据集，该数据集 将促进具有不同艾滋病毒数据类型的新的分子流行病学分析。我们创造的这一组合 数据集(通过去身份、匿名化、记录链接和遗传分析过程)将作为 有类似分散的艾滋病毒数据来源和可获得的艾滋病毒基因类型的社区的模式。 随后，我们将使用这个数据集进行创新的“第二代”系统发育研究。首先，我们将 描述艾滋病毒在主要受影响人群中的传播模式，包括在外国出生的西雅图居民和 青少年男男性接触者。我们假设，系统发育连锁分析将表明，超过80%的非洲人- 出生病例是进口病例，但不到50%的拉丁裔病例是输入病例，对公共卫生有重要影响。我们也 假设对我们的联合数据集的系统发育分析将揭示青少年MSM经常 在有较老MSM的集群中发现，发病率高于基线预期，表明年龄差异 在西雅图的这群人中，配对可能在推动传播方面发挥作用。第二，我们将与 克里斯托夫·弗雷泽和奥利弗·拉特曼(伦敦帝国理工学院)估计， 西雅图从感染和护理的每个阶段产生连续体。为这篇关于西雅图的尖端分析 数据集，我们将扩展最初用于研究的数据驱动的临床和系统发育方法 男男性接触者在荷兰的传播。我们假设西雅图50%的传输来自 未确诊的人，而未保留在护理中的患者的传播比之前估计的要少。 西雅图是实施这一项目的理想地点，因为即使拥有丰富的公共卫生资源，积极和 学术界和政府之间的密切合作，以及在艾滋病护理方面取得的巨大成功 瀑布，疫情仍在持续。

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.