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）：本申请是为Ann Dennis MD颁发的K08奖，他是北卡罗来纳大学传染病科医学助理教授，他正在培训成为HIV传播，流行病学和预防的独立研究者。尽管艾滋病毒治疗和预防取得明显进步，但在美国东南部，新的艾滋病毒诊断仍在继续，那里的少数族裔和与男性发生性关系的男性仍然存在很大的差异。需要创新的方法来成功减少这些脆弱群体中的艾滋病毒感染。系统发育HIV传播网络或“群集”的鉴定是来自具有共享HIV传播的个体的高度相关序列，它在人群水平上对HIV传播的结构提供了独特的见解，这是无法通过接触跟踪或其他患者报告的病史获得的。与临床和人口统计数据相结合，这些传输簇可能会为预防艾滋病毒预防的新目标提供针对持续传播风险最高风险的群体。总体研究目标是表征北卡罗来纳州的局部系统发育集群，并研究系统发育在公共卫生环境中的使用以靶向将来的干预措施。拟议的研究将采用创新的分子流行病学方法来重建传播簇，使用从常规临床护理期间发送的抗逆转录病毒抗性测试提取的大量HIV POL序列。该研究的目的是：1）确定在大量的新临床和已建立的HIV病例中，新兴或扩大HIV传播簇的时间和临床特征； 2）评估普遍艾滋病毒病例的更高密度抽样对检测传播簇的影响，并表征全州流行病结构； 3）确定将HIV序列分析纳入限制地理区域中常规HIV监测中的可行性。 Dennis博士的指导团队将包括主要导师Joseph Eron，医学博士，UNC医学教授，拥有20多年的HIV临床和流行病学研究经验。两名副官员将提供艾滋病毒流行病学和系统发育学专业知识的互补领域：威廉·米勒（William Miller），医学博士，博士，MPH，MPH，UNC的流行病学和医学副教授，其研究侧重于HIV流行病学；伦敦大学学院病毒学家斯蒂芬·豪（Stephane Hue）是国际公认的HIV系统发育学专家和UNC合作者的专家。丹尼斯博士的培训计划与拟议的研究的目标：建立艾滋病毒流行病学的稳固基础，包括监测和暴发研究，包括艾滋病毒流行病学；扩展系统发育分析的技能，以整合时间缩放和地理数据；并探讨围绕HIV预防系统发育学的道德问题。培训将通过教学课程，讲习班和实践的结合来完成。这些培训和研究活动将使丹尼斯博士能够成熟成为一个独立的研究者，并为R01实施实时系统发育以直接预防干预措施和跟踪HIV发病率的趋势提供了基础。