Next-Generation Phylodynamics-targeted Partner Service Models for Combined HIV Prevention

以系统动力学为目标的合作伙伴服务模型(P2M)项目旨在引导和快速转变 以分子艾滋病毒监测(MHS)为基础的预防干预措施的公共卫生实施进展 朝着消除艾滋病毒迈出的关键一步。P2M寻求研究和优化正在出现的新的国家指导： 美国疾病控制与预防中心2017年3月关于卫生部门的艾滋病毒群组指导工作组的建议 实施具有临床艾滋病毒耐药基因型的MHS，现在建议在入院时进行护理。这些HIV-1病毒 POL序列可以用来识别基因相似的艾滋病毒携带者的“分子簇”。这个 MHS的首要目标是识别处于风险环境中的人。这些人是潜在的来源， 或新艾滋病毒传播的接受者，并被定义为：1)新的艾滋病毒血清阳性者(包括最近/急性 感染)；2)以前已知的具有可检测到的病毒载量的艾滋病毒血清阳性者(无论是否在护理中)；以及3)高危艾滋病毒 血清阴性。这些人在风险环境中的收益率是衡量以下因素有用性的重要指标 基于MHS的合作伙伴服务或其他网络招聘程序(即2步)，将在P2M中进行检查。 因此，P2M的目标是严格检验假设：(A)分析更接近HIV时间的分子簇数据 诊断将增加风险环境成员的收益；以及(B)使用先进的 我们团队创新的合作伙伴和网络服务方法也将提高收益和改善 公共卫生综合干预的有效性。然而，进行一系列的 用随机试验来检验这些假说。然而，建模方法最适合于提供 指导当存在多种方法和可想象的条件时，上下文不适合于 研究试验，以及可能出现多个下游结果的地方。对于P2M，这一多- 机构调查小组(来自休斯顿和芝加哥)将建立在现有艾滋病毒追踪合作的基础上， 受艾滋病毒影响最大的人群和现有的基于代理人的艾滋病毒传播的观察性队列 指导干预并确定干预优先顺序的模型(ABM)。因此，我们的目标是：1)确定相对 针对HIV踪迹衍生分子簇的合作伙伴服务与合作伙伴服务的有效性比较 目前在没有分子簇定位(护理标准)的情况下提供的服务，以帮助有风险的人 环境。目标2)通过基于代理的参数化来优化几个集群大小和时间阈值 使用现有队列数据建立模型，根据以下各项得出风险环境中最佳的个人类别：1) 分子簇的时间识别；2)分子簇的数量和大小；以及3)实时与延迟 合作伙伴服务对集群增长的响应。目标3a)结合分子的相对有效性模型 监控和下一代合作伙伴服务-两步、三步和社交网络推荐-最佳收益 目标3b)探索模拟艾滋病毒预防干预措施(即。准备)和他们的 成本，因为它们是在真实的分子集群和合作伙伴/网络服务战略中建模的。

The Phylodynamics-targeted Partner service Models (P2M) project aims to guide and transform the rapidly evolving public health implementation of molecular HIV surveillance (MHS) based prevention interventions as a critical step towards HIV elimination. P2M seeks to study and optimize emerging new national guidance: The CDC's March 2017 recommendations of the HIV Cluster Guidance Working Group on health department implementation of MHS with clinical HIV resistance genotypes, now recommended at entry to care. These HIV-1 pol sequences can be used to identify “molecular clusters” of persons with genetically similar HIV. The overarching goal of MHS is to identify persons within the risk environment. These persons are potential sources, or recipients, of new HIV transmissions, and defined as: 1) new HIV seropositives (including recent/acute infections); 2) previously known HIV seropositives with detectable viral load (in care or not); and 3) at-risk HIV seronegatives. The yield of these persons in the risk environment is an important metric of the usefulness of MHS-based partner services or other network recruitment procedures (ie 2-step) that will be examined in P2M. Thus, P2M aims to rigorously test the hypotheses that: (a) analyzing molecular cluster data closer to time of HIV diagnosis will increase the yield of risk environment members; and (b) targeted prevention using advanced partner and network service approaches our team has innovated will also increase yield and improve effectiveness of public health combination interventions. It is not feasible, however, to conduct a series of randomized trials to test these hypotheses. Modeling approaches, however, are best suited for providing guidance when multiple approaches and conceivable conditions exist, the contexts do not lend themselves to research trials, and where multiple downstream outcomes are possible. For P2M, members of this multi- institutional investigative team (from Houston and Chicago) will build upon existing HIV TRACE collaborations, observational cohorts of populations most impacted by HIV and an existing Agent-Based HIV transmission model (ABM) to guide and prioritize interventions. Accordingly, we aim to: Aim 1) Determine the relative effectiveness of partner services targeted to HIV TRACE derived molecular clusters compared to partner services as currently delivered without molecular cluster targeting (standard of care) to yield persons in the risk environment. Aim 2) Optimize several cluster size and time thresholds by parameterizing an agent-based model with existing cohort data that best yield categories of individuals in the risk environment based upon: 1) time-to-molecular cluster identification; 2) molecular cluster number and size; and 3) real-time versus delayed partner services response to cluster growth. Aim 3a) Model relative effectiveness of combined molecular surveillance and next-generation partner services – 2-step, 3-step and social network referral – that best yield persons in the risk environment; Aim 3b) Explore simulated HIV prevention interventions (ie. PrEP) and their cost as they are modeled within real-world molecular cluster and partner/network service strategies.