Timely monitoring and response to HIV transmission networks for intensified prevention

项目摘要 跟踪基于人口的艾滋病毒传播动态对于设计和监测有效的 干预措施。尽管开展了广泛的预防工作，但艾滋病毒的发病率在1999年的一些亚群中并没有下降。 美国（US），包括男男性行为者（MSM）。这种差异在以下国家中很明显： 美国南部是全国流行病的中心，在新的和流行的疾病中负担最重。 感染.艾滋病毒感染的显著差异存在于种族/民族和危险行为，但也存在于 地理;与其他区域相比，大城市地区以外报告的病例比例较高。 描述美国南部的艾滋病毒传播动态可以确定正在进行的传播网络， 有针对性的预防措施可能对降低当地发病率更有效的集群。但 这些措施要取得成功，就需要及时查明和应对新出现的或不断扩大的集群。 结合流行病学和临床监测的HIV序列的前瞻性系统发育分析 数据将有助于及时发现和监测传输网络。当结合 可以更好地预测非线性动力学建模、集群扩展和传输动力学， 评估干预措施的影响。 我们的总体假设是：1）前瞻性系统发育聚类分析可以及时识别 通过常规监测不明显的传播链，2）在扩大的集群中发现的人员 代表本地传播的前沿，即最近感染，3）针对日益增长的 集群将确定更高比例的近期感染，并最终降低发病率。这些假设 将在北卡罗来纳州（NC）进行讨论，有三个具体目标：目标1：描述人口统计学和 使用新报告的艾滋病毒感染者传播艾滋病毒的地理特征 系统发育聚类、病毒载量和危险行为;目的2：评估艾滋病毒聚类扩展并告知 通过整合大规模深度测序和涉及以下病例的接触网络， 新诊断的艾滋病毒感染者;目标3：对聚集性伴侣进行初步评估 服务干预中断艾滋病毒传播网络。 这些目标将通过与NC部门合作的战略组合来实现 卫生与公众服务部一个全州范围的前瞻性，自动聚类分析系统（nextHIV）将被 评估。来自参考实验室的序列和来自公众的诊断标本的深度测序 将对测试地点进行近实时分析。将用详细的流行病学数据来描述集群 包括HIV病毒载量和接触网络。概念验证、面向群集的合作伙伴服务 将在艾滋病毒高负担的11个县区域评估干预措施。系统动力学和数学 将利用建模来评估集群扩展和干预措施的潜在影响。

PROJECT SUMMARY Tracking population-based HIV transmission dynamics is critical to design and monitor effective interventions. Despite widespread prevention, HIV incidence has failed to decline among some subgroups in the United States (US) including young men who have sex with men (MSM). Such disparities are notable in the Southern US which is at the epicenter of the national epidemic with the greatest burden in new and prevalent infections. Significant disparities in HIV infection exist based on race/ethnicity and risk behaviors, but also in geography; a higher proportion of cases are reported outside large urban areas compared to other regions. Delineating HIV transmission dynamics in the Southern US can identify ongoing transmission networks or clusters where targeted prevention measures may be more impactful at reducing local incidence. However, the success of such measures requires timely identification and response to emerging or expanding clusters. Prospective phylogenetic analyses of HIV sequences integrated with epidemiologic and clinical surveillance data would facilitate the timely detection and monitoring of transmission networks. When combined with phylodynamic modeling, cluster expansion and transmission dynamics could be better predicted and the impact of interventions assessed. Our overall hypotheses are: 1) Prospective phylogenetic cluster analysis allows timely identification of transmission chains not apparent through routine surveillance, 2) Persons identified in expanding clusters represent the leading edge of local transmission, i.e. recent infection, 3) Targeting prevention towards growing clusters will identify a higher proportion of recent infections and ultimately reduce incidence. These hypotheses will be addressed in North Carolina (NC) with three specific aims: Aim 1: To describe the demographic and geographical characteristics of HIV transmission involving persons with newly reported HIV infection using phylogenetic clustering, viral load, and risk behaviors; Aim 2: To assess HIV cluster expansion and inform phylodynamic models by integrating large-scale deep sequencing and contact networks involving cases with newly diagnosed HIV infection; Aim 3: To conduct a preliminary assessment of a cluster-directed partner services intervention to interrupt HIV transmission networks. These aims will be addressed through a combination of strategies in collaboration with the NC Department of Health and Human Services. A statewide prospective, automated cluster analysis system (nextHIV) will be evaluated. Sequences from reference laboratories and deep sequencing of diagnostic specimens from public testing sites will be analyzed in near-real time. Clusters will be characterized with detailed epidemiological data including HIV viral loads and contact networks. A proof-of-concept, cluster-directed partner services intervention will be assessed in an 11 county region with high HIV burden. Phylodynamic and mathematical modeling will be used to assess cluster expansion and the potential impact of interventions.