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: 8731404
• 负责人: Ann Dennis
• 金额: $ 16.91万
• 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 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731404
• 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; Contact Tracing; County; Data; Data Set; Databases; Detection; Development; Diagnosis; Disease Outbreaks; Doctor of Philosophy; Educational workshop; Epidemic; Epidemiologic Studies; Epidemiology; Ethical Issues; Event; Foundations; Future; Genetic; Genotype; Geographic Locations; Growth; HIV; HIV Infections; HIV diagnosis; Health; Health Resources; Hot Spot; Incidence; Individual; Infection; Intervention; Investigation; Knowledge; Lead; Link; London; Medical Surveillance; Medicine; Mentors; Methods; Minority; 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; Simulate; Solid; Structure; Testing; Time; Training; Training Activity; Translating; Universities; Vulnerable Populations; base; clinical care; cohort; college; data exchange; density; experience; high risk; innovation; insight; member; men who have sex with men; prevent; professor; public health relevance; 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: ) 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）：本申请是为北卡罗来纳州大学传染病系医学助理教授Ann Dennis MD颁发的K 08奖，他正在接受培训，成为艾滋病毒传播，流行病学和预防方面的独立调查员。尽管艾滋病毒治疗和预防取得了显着进展，但美国东南部仍有新的艾滋病毒诊断，少数民族和男男性行为者之间仍然存在显着差异。需要创新的方法来成功地减少这些弱势群体中的艾滋病毒感染事件。系统发育的HIV传播网络或“簇”的鉴定，这是高度相关的序列，从共享的HIV传播的个人，提供了独特的洞察艾滋病毒传播的结构在人口水平上，不能通过接触追踪或其他患者报告的历史。结合临床和人口统计数据，这些传播聚集性可能会提供新的目标，以指导针对持续传播风险最高的群体的艾滋病毒预防工作。总体研究目标是描述北卡罗来纳州的地方系统发育簇，并调查在公共卫生环境中使用基因组学来针对未来的干预措施。这项拟议的研究将采用分子流行病学的创新方法，利用从常规临床护理期间发送的抗逆转录病毒耐药性检测中提取的HIV pol序列的大型储存库来重建传播集群。该研究的目的是：）在一个新的和确定的艾滋病毒病例的大型临床队列中确定新出现或扩大的艾滋病毒传播集群的时间和临床特征; 2）评估流行艾滋病毒病例的高密度采样对传播集群检测的影响，并描述全州范围内的流行结构; 3）确定在有限的地理区域内将HIV序列分析纳入常规HIV监测的可行性。Dennis博士的指导团队将由主要导师Joseph Eron，医学博士，在HIV临床和流行病学研究方面拥有20多年经验的医学教授组成。两位共同导师将提供艾滋病毒流行病学和遗传学专业知识的互补领域：William米勒，医学博士，公共卫生硕士，流行病学和医学副教授，其研究重点是艾滋病毒流行病学;和Stephane Hue，博士，伦敦大学学院的病毒学家，自2010年以来，他是国际公认的艾滋病毒遗传学专家和艾滋病合作者。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，包括监测和疫情调查;扩大系统发育分析的技能，整合时间尺度和地理数据;并探讨艾滋病毒预防中围绕遗传学的伦理问题。培训将通过教学课程，研讨会和实习相结合来完成。这些培训和研究活动将使丹尼斯博士成长为一名独立的研究者，并为以下方面提供基础： 一个R 01，用于实施实时监测，以指导预防干预措施，并跟踪艾滋病毒发病率的趋势。