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）：本申请旨在为北卡罗来纳大学传染病科医学助理教授 Ann Dennis MD 申请 K08 奖，她正在接受培训，成为 HIV 传播、流行病学和预防领域的独立研究者。尽管在艾滋病毒治疗和预防方面取得了显着进展，但美国东南部地区仍有新的艾滋病毒诊断，那里的少数族裔和男男性行为者之间仍然存在巨大差异。需要创新方法来成功减少这些弱势群体中的艾滋病毒感染事件。系统发育艾滋病毒传播网络或“簇”的识别是来自具有共同艾滋病毒传播的个体的高度相关的序列，为人口水平上的艾滋病毒传播结构提供了独特的见解，而这是通过接触者追踪或其他患者报告的历史无法获得的。与临床和人口统计数据相结合，这些传播集群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当地系统发育集群的特征，并调查系统发育在公共卫生环境中的应用，以制定未来的干预措施。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测试中提取的 HIV pol 序列的大型存储库来重建传播集群。该研究的目的是： ) 确定在新发和已确诊的艾滋病毒病例的大型临床队列中新出现或扩大的艾滋病毒传播集群的时间和临床特征； 2) 评估对流行的艾滋病毒病例进行高密度采样对发现传播簇的影响，并描述全州流行病结构的特征； 3) 确定将 HIV 序列分析纳入特定地理区域的常规 HIV 监测的可行性。 Dennis 博士的指导团队将由主要导师 Joseph Eron 医学博士组成，他是北卡罗来纳大学医学教授，在 HIV 临床和流行病学研究方面拥有 20 多年的经验。两位共同导师将在艾滋病毒流行病学和系统发育学领域提供互补的专业知识：William Miller，医学博士、哲学博士、公共卫生硕士，北卡罗来纳大学流行病学和医学副教授，其研究重点是艾滋病毒流行病学；丹尼斯博士的培训计划与拟议的研究目标相关：为艾滋病毒流行病学（包括监测和疫情调查）奠定坚实的基础；扩展整合时间尺度和地理数据的系统发育分析技能；并探讨围绕艾滋病毒预防的系统发育学的伦理问题。培训将通过教学课程、研讨会和实习相结合的方式完成。这些培训和研究活动将使丹尼斯博士成长为一名独立研究者，并为 R01 实施实时系统发育以指导预防干预措施并跟踪艾滋病毒发病率趋势。