Real Time Phylogeny and Contact Tracing to Disrupt HIV Transmission

实时系统发育和接触者追踪以阻断HIV传播 摘要 预防艾滋病毒传播仍然是一项重大的全球挑战，需要创新的方法来实现其 颠覆。虽然实际的传输网络是未知的，但具有社会和系统进化的特征 网络可以指导预防干预措施。接触者追踪是目前公共卫生工具，以派生社会 建立网络，识别、通知、检测新诊断的艾滋病毒病例，并将其链接到护理伙伴。系统发育 对现有序列的分析被用于研究流行病的特征，并促进了疫情的爆发 调查。然而，系统发育与接触者追踪的实时集成在公共卫生、州- Wide Level尚未进行评估。我们建议前瞻性地将系统发育分析与接触相结合。 实时追踪，并评估这种整合对罗德岛艾滋病毒感染的影响。我们 假设实时使用来自系统发育推断的信息可以增强接触者追踪， 改进艾滋病毒检测、诊断和与护理的联系，并阻断传播。具体目标是：(1) 对患者级别的序列数据进行实时系统发育分析；(2)增强系统发育推理 通过增加抽样和更全面的测试；以及(3)评估实时集成 与接触者追踪努力的系统发育。我们将开发和自动化工具，以结合系统发育和 系统动力学推断到接触者追踪，探索其增强，并评估其实时影响， 特别考虑主要人群，如男男性行为者、静脉注射吸毒者和 对艾滋病毒有抗药性。我们预计这种方法将改善识别和联系，以照顾 未意识到感染的个人、与护理无关的意识到感染的个人，以及 有很高的感染风险。这一建议的主要前提是系统发育网络包含 可以扩大社会网络并影响艾滋病毒传播的信息。如果我们的假设是正确的， 这项研究将对艾滋病的预防和护理连续性产生很大影响，并将阻断艾滋病的传播。 罗德岛。我们的多学科临床医生团队加强了我们研究方法的严谨性， 公共卫生官员、统计学家、生物信息学家、进化和分子生物学家，与我们的 相关现有数据和专业知识，国家面积小，学术封闭强大--公众 健康伙伴关系。此外，还直接涉及重要和基本的道德考量，并 自始至终都是这样。这种方法将使结果具有概括性和可持续性，使重点 资源分配以及不断执行和推广调查结果。2013年，美国联邦调查局局长 国际扶轮卫生部宣布的愿景是在接下来的几年内在该州实现新的艾滋病毒感染人数为零 然而，五年来，高风险网络之间传播的明显增加阻碍了进展。这 该提案将有助于使小型国际扶轮更接近其成为第一个零新感染和 展示集中努力如何防止艾滋病毒在国际扶轮及其他地区的传播。

Real Time Phylogeny and Contact Tracing to Disrupt HIV Transmission Kantor, Rami MD SUMMARY Prevention of HIV transmission is still a major global challenge, and innovative methods are needed for its disruption. Though actual transmission networks are unknown, characterizing social and phylogenetic networks can guide prevention interventions. Contact tracing is the current public health tool to derive social networks and identify, notify, test and link to care partners of newly-diagnosed HIV cases. Phylogenetic analysis of available sequences is used in research to characterize epidemics and has facilitated outbreak investigations. However, real time integration of phylogenetics with contact tracing on a public health, state- wide level has not been evaluated. We propose to prospectively integrate phylogenetic analysis with contact tracing in real time, and evaluate the impact of such integration on HIV infection in Rhode Island (RI). We hypothesize that real time use of information from phylogenetic inference can enhance contact tracing, improve HIV testing, diagnoses and linkage to care, and disrupt transmission. The Specific Aims are to: (1) Conduct real time phylogenetic analyses of patient-level sequence data; (2) Augment phylogenetic inference by increased sampling and more comprehensive testing; and (3) Evaluate the benefit of real time integration of phylogenetics with contact tracing efforts. We will develop and automate tools to incorporate phylogenetic and phylodynamic inference into contact tracing, explore its enhancement, and evaluate its real time impact, with special consideration of key populations like men who have sex with men, intravenous drug users and persons with HIV drug resistance. We expect that this approach will improve identification and linkage to care of infected-unaware individuals, infected-aware individuals not linked to care, and uninfected individuals that are at high risk of infection. The main premise of this proposal is that phylogenetic networks contain information which can expand social networks and impact HIV transmission. If our hypothesis is correct, this research will have high impact on HIV prevention and the care continuum and disrupt HIV transmission in Rhode Island. The rigor of our research approach is strengthened by our multidisciplinary team of clinicians, public health officials, statisticians, bioinformaticians, evolutionary and molecular biologists, combined with our relevant existing data and expertise, the small size of the state and the strong and close academic-public health partnership. Furthermore, important and essential ethics considerations are directly addressed and incorporated throughout. Such an approach will make results generalizable and sustainable, allowing focused resource allocation and continuous implementation and generalization of findings. In 2013 the Director of the RI Department of Health declared the vision of ‘Getting to Zero’ new HIV infections in the state within the next five years, however apparent increases in transmission among high risk networks has impeded progress. This proposal will help bring small RI closer to its goal of being the first state to get to zero new infections and demonstrate how focusing efforts can prevent HIV transmission in RI and beyond.