Using Phylogenetics to Elucidate HIV Transmission Patterns and Inform Prevention

利用系统发育学阐明艾滋病毒传播模式并为预防提供信息

• 批准号: 9280868
• 负责人: Ann Dennis
• 金额: $ 19.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9280868
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Acute; Age; Antiretroviral resistance; Appearance; Area; Award; Base Sequence; Behavioral; Characteristics; Clinic; Clinical; Clinical Research; Cohort Analysis; Communicable Diseases; Computing Methodologies; Contact Tracing; County; Data; Data Set; Databases; Detection; Development; Diagnosis; Disease Outbreaks; Doctor of Philosophy; Educational workshop; Epidemic; Epidemiologic Monitoring; Epidemiology; Ethical Issues; Event; Foundations; Future; Genetic; Genotype; Geographic Locations; Geography; Growth; HIV; HIV Infections; HIV diagnosis; Health; Health Resources; Heterosexuals; Hot Spot; Incidence; Individual; Infection; International; Interruption; Intervention; Investigation; Knowledge; Lead; Link; London; Medicine; Mentors; Methods; Molecular; Molecular Epidemiology; Newly Diagnosed; North Carolina; Patients; Pattern; Persons; Phylogenetic Analysis; Phylogeny; Population; Positioning Attribute; Prevention; Prevention Measures; Prevention Research; Prevention program; Preventive Intervention; Public Health; Race; Recording of previous events; Reporting; Research; Research Activity; Research Personnel; Research Training; Risk; Running; Sampling; Sequence Analysis; Signal Transduction; Solid; Structure; Testing; Time; Training; Training Activity; Translating; Universities; Vulnerable Populations; base; clinical care; cohort; college; data exchange; density; epidemiologic data; epidemiology study; experience; high risk; innovation; insight; member; men who have sex with men; mid-career faculty; prevent; professor; prospective; public health relevance; racial minority; reconstruction; repository; skills; surveillance strategy; tool; trait; transmission process; trend

DESCRIPTION (provided by applicant): This application is for a K08 award for Ann Dennis MD, an Assistant Professor of Medicine in the Division of Infectious Diseases at the University of North Carolina, who is training to become an independent investigator in HIV transmission, epidemiology, and prevention. Despite marked advances in HIV treatment and prevention, new HIV diagnoses continue in the southeastern US where significant disparities still exist among racial minorities and men who have sex with men. Innovative methods are needed to successfully decrease incident HIV infections among these vulnerable groups. The identification of phylogenetic HIV transmission networks or "clusters", which are highly related sequences from individuals with shared HIV transmission, offers unique insight into the structure of HIV transmission on a population level that cannot be obtained through contact tracing or other patient-reported history. Paired with clinical and demographic data, these transmission clusters may provide new targets to direct HIV prevention efforts for groups at highest risk for ongoing transmission. The overall research objective is to characterize local phylogenetic clusters in North Carolina and investigate the use of phylogeny in the public health setting to target future interventions. The proposed study will employ innovative methods in molecular epidemiology to reconstruct transmission clusters using large repositories of HIV pol sequences extracted from antiretroviral resistance testing sent during routine clinical care. The aims of the study are to: 1) Identify the temporal and clinical features of emerging or expanding HIV transmission clusters in a large clinical cohort of new and established HIV cases; 2) Assess the effect of higher density sampling of prevalent HIV cases on the detection of transmission clusters and characterize the statewide epidemic structure; and 3) Determine feasibility of incorporating HIV sequence analysis into routine HIV surveillance in a circumscribed geographic area. Dr. Dennis's mentoring team will consist of primary mentor Joseph Eron, MD, Professor of Medicine at UNC with over 20 years of experience in HIV clinical and epidemiologic research. Two co-mentors will offer complementary areas of expertise in HIV epidemiology and phylogenetics: William Miller, MD, PhD, MPH, Associate Professor of Epidemiology and Medicine at UNC whose research focuses on HIV epidemiology; and Stephane Hue, PhD, virologist at University College London, an internationally recognized expert in HIV phylogenetics and UNC collaborator since 2010. Dr. Dennis' training plan links to the proposed research aims: establish a solid foundation in HIV epidemiology including surveillance and outbreak investigation; expand skills in phylogenetic analyses integrating time- scaled and geographic data; and explore ethical issues surrounding phylogenetics in HIV prevention. Training will be accomplished through a combination of didactic courses, workshops, and practicums. These training and research activities will allow Dr. Dennis to mature into an independent investigator and provide a basis for an R01 to implement real-time phylogeny to direct prevention interventions and track trends in HIV incidence.

描述(由申请人提供)：此申请表是为了授予Ann Dennis MD K08奖项，她是北卡罗来纳大学传染病系医学助理教授，正在接受培训，希望成为艾滋病毒传播、流行病学和预防方面的独立调查员。尽管在艾滋病毒治疗和预防方面取得了显著进展，但美国东南部仍有新的艾滋病毒诊断病例，那里的少数民族和男男性行为者之间仍然存在显著的差异。需要创新的方法来成功地减少这些弱势群体中发生的艾滋病毒感染。识别系统发育的艾滋病毒传播网络或“簇”是来自共享艾滋病毒传播的个人的高度相关的序列，提供了对人群一级艾滋病毒传播结构的独特洞察，这是通过接触者追踪或其他患者报告的病史无法获得的。结合临床和人口学数据，这些传播集群可能提供新的目标，以指导持续传播风险最高的人群的艾滋病毒预防工作。总体研究目标是描述北卡罗来纳州当地的系统发育集群，并调查系统发育在公共卫生环境中的使用情况，以确定未来干预措施的目标。这项拟议的研究将使用分子流行病学中的创新方法，使用从常规临床护理期间发送的抗逆转录病毒耐药性测试中提取的艾滋病毒Poll序列的大型存储库来重建传播集群。这项研究的目的是：1)在一大批新的和确定的艾滋病毒病例的临床队列中，确定出现或扩大的艾滋病毒传播集群的时间和临床特征；2)评估对流行的艾滋病毒病例进行高密度抽样对检测传播集群的影响，并描述全州的流行结构；以及3)确定将艾滋病毒序列分析纳入限定地理区域的常规艾滋病毒监测的可行性。丹尼斯博士的指导团队将由主要导师约瑟夫·埃伦医学博士组成，他是北卡罗来纳大学的医学教授，在艾滋病毒临床和流行病学研究方面拥有20多年的经验。两位共同导师将提供艾滋病毒流行病学和系统发生学方面的互补专业知识：威廉·米勒，医学博士，博士，公共卫生硕士，北卡罗来纳大学流行病学和医学副教授，主要研究艾滋病毒流行病学；斯蒂芬·休，博士，伦敦大学学院病毒学家，国际公认的艾滋病毒系统发生学专家，自2010年以来一直是北卡罗来纳大学的合作者。丹尼斯博士的培训计划与拟议的研究目标相联系：在艾滋病毒流行病学方面建立坚实的基础，包括监测和暴发调查；扩大将时间尺度和地理数据结合在一起的系统发育分析技能；以及探索艾滋病毒预防中围绕系统发育的伦理问题。培训将通过授课课程、研讨会和实践相结合的方式完成。这些培训和研究活动将使丹尼斯博士能够成熟为一名独立的研究员，并为R01实施实时系统发展史提供基础，以指导预防干预和跟踪艾滋病毒发病率的趋势。