Estimation of HIV Transmission Dynamics Using Genetic Sequences of Virus

描述(由申请人提供)：本建议书描述了密歇根大学安娜堡分校流行病学系助理研究科学家Erik Volz的四年职业发展和培训计划。培训将有助于发展流行病学的职业生涯，重点是传染病，特别是艾滋病毒和其他性传播感染。 该培训计划将使沃尔茨博士获得艾滋病流行病学专业知识所必需的领域的技能，同时在他已经建立了良好的出版记录的领域进行大量研究。沃尔茨博士将接受一个由三名教员组成的团队的指导，他们的经验范围从传染病的复杂系统建模到艾滋病毒感染的微生物学和病理学，以及病毒的进化。密歇根大学公共卫生学院是寻求发展独立调查员职业生涯的初级教员的绝佳场所。大量的研究人员和博士后研究员可以作为潜在的合作者和正在进行的工作的观众。 该奖项支持的研究将涉及使用艾滋病毒基因数据的新来源来拟合艾滋病毒流行的模型。数学流行病学、免疫学和系统发育学的结合被称为“系统动力学”，沃尔茨博士在将传染病流行的传统模型与系统发生树所描述的艾滋病毒进化相统一所必需的理论方面取得了最新进展。最近证明了系统动力学方法的潜力，因为对大流行H1N1的基本繁殖数R0的第一次估计来自对数十个流感基因序列的分析，而不是来自传统的流行病学监测数据。沃尔茨博士希望改进这些方法，并将其发展成为流行病学家从事艾滋病毒监测的实用工具。将与密歇根州社区卫生部门合作，分析自2004年以来从新诊断的个人中收集的数千个艾滋病毒序列的数据库。通过将系统动力学模型应用于这一大组序列，沃尔茨博士将试图回答有关艾滋病毒传播模式的长期问题。这项研究将产生对R0的新估计，感染后传播的时间分布，在急性和早期艾滋病毒感染期间发生的传播比例，感染和传播风险的人口决定因素，以及行为异质性和性网络结构。 公共卫生相关性：遏制艾滋病毒大流行需要有效的监测、频繁的检测和对新感染的快速诊断。未得到充分利用的数据来源来自病毒本身。病毒的基因序列带有流行病学动力学的指纹，这项建议的目的是利用为常规耐药性测试收集的艾滋病毒序列来表征艾滋病毒传播的分布和决定因素。

DESCRIPTION (provided by applicant): This proposal describes a four year career development and training plan for Erik Volz, an Assistant Research Scientist in the Department of Epidemiology at the University of Michigan-Ann Arbor. Training will aid with the development of a career in Epidemiology with a focus on infectious diseases, especially HIV and other sexually transmitted infections. The training program will allow Dr. Volz to acquire skills in areas necessary for expertise in the field of HIV epidemiology while conducting substantial research in areas where he already has established a strong publishing record. Dr. Volz will be mentored by a team of three faculty with experience ranging from complex systems modeling of infectious diseases to the microbiology and pathology of HIV infection and the evolution of viruses. The School of Public Health at the University of Michigan is an excellent venue for junior faculty seeking to develop a career as an independent investigator. A large community of research faculty and postdoctoral fellows are available as potential collaborators and as an audience for work in progress. Research supported by this award will concern the use of novel sources of HIV genetic data for fitting models of the HIV epidemic. The union of mathematical epidemiology, immunology and phylogenetics has been dubbed "phylodynamics", and Dr. Volz has made recent progress on the theory necessary to unify traditional models of infectious disease epidemics with the evolution of HIV described by phylogenetic trees. The potential of phylodynamic methods was demonstrated recently as the first estimates of the fundamental reproduction number, R0, for pandemic H1N1 came from the analysis of several dozen influenza genetic sequences, not from traditional epidemiological surveillance data. Dr. Volz hopes to refine these methods and develop them into a practical tool for epidemiologists engaging in HIV surveillance. A collaboration will be established with the Michigan Department of Community Health to analyze a database of several thousand HIV sequences collected from newly diagnosed individuals since 2004. By applying phylodynamic models to this large set of sequences, Dr. Volz will attempt to answer longstanding questions about the transmission patterns of HIV. This research will generate novel estimates of R0, the temporal distribution of transmissions post-infection, the fraction of transmissions that happen during acute and early HIV infection, demographic determinants of infection and transmission risk, and behavioral heterogeneity and sexual network structure. Public Health Relevance: Stemming the HIV pandemic requires effective surveillance, frequent testing, and rapid diagnosis of new infections. An under-utilized source of data comes from the virus itself. The genetic sequence of virus bears the fingerprint of epidemiological dynamics, and the objective of this proposal is to characterize the distribution and determinants of HIV transmission using HIV sequences collected for routine drug-resistance testing.