Determinants of HIV Transmission

描述（由申请人提供）： 迫切需要有效的艾滋病毒预防战略，有效的艾滋病毒疫苗是大幅降低艾滋病毒新感染率的最佳长期希望。为了实现这一目标，我们目前对艾滋病毒传播的生物学和流行病学的了解仍然有限。该计划项目将侧重于识别和系统评估最近感染艾滋病毒的个人和将艾滋病毒传播给他们的性伴侣（传播对），以阐明和量化有助于传播的流行病学，行为，生物学，病毒学和宿主因素。 圣地亚哥原发性感染研究小组在招募急性和最近感染艾滋病毒的个体及其传播伙伴方面有着悠久而成功的历史。通过新的方法来扩大我们对这些研究参与者的识别，如临床和标本核心中所述，我们将在项目1中解决（传输概率）：（目标1）每次接触的传播概率（J），（目标2）伴侣更换率（c），（目标3）传染期持续时间（D），从而确定该人群中HIV的生殖数（R 0）。这些调查将与项目2（传播相关因素）相辅相成，项目2将确定和量化艾滋病毒性传播的重要生物（目标1）、病毒（目标2）和宿主（目标3）相关因素的贡献。最重要的是，这项研究将允许准确估计潜在的预防策略或候选疫苗的预期功效，这是基于对目标人群正在进行的风险行为的估计以及对有助于艾滋病毒传播的病毒和宿主因素的全面了解。行政核心（核心A）将在协调本项目的行政、财政、数据和统计支持方面发挥核心作用，并提供科学支持，促进研究者和合作者之间的协同互动，这对互动项目的成功至关重要。临床和标本核心（核心B）将识别、招募和入组研究受试者，并采集、处理、储存和管理满足两个拟定研究项目目标所需的临床标本。 项目1：传输概率（Strathdee，S.） 项目1描述（由申请人提供）： 建立预防干预模型需要深入了解影响艾滋病毒传播的流行病学和生物学因素。拟议方案项目的项目1通过检查每次接触传播概率（P）、伴侣更换率/接触率（c）和感染持续时间（D）来解决艾滋病毒传播的流行病学决定因素，这些因素都有助于生殖数（R 0 = pcD），定义为完全易感人群中单次感染引起的继发感染的平均数。为了实现这一目标，我们将致力于以下具体目标：目标1：每次接触传播概率（P）-将估计每次接触性传播艾滋病毒的概率，同时考虑源伴侣的艾滋病毒感染阶段、病毒和细菌性传播感染的存在、包皮环切术状况以及项目2中研究的其他生物辅助因素。插入性肛交与接受性肛交的传播概率的绝对和相对差异也将被考虑。目标二：伴侣更换率（c）-将在个人、伙伴关系和网络各级审查伴侣选择在艾滋病毒感染和传播风险中的作用。在个人一级，将审查性行为次数与性伴侣人数对艾滋病毒风险的相对贡献。在伙伴关系一级，将比较传播性伙伴关系和血清一致性非传播性伙伴关系的风险特征。在网络一级，将阐明基于个人在用于会见性伴侣的场所网络内的位置的艾滋病毒感染和传播风险，以及传播集群中的相关因素。目标3：传染性持续时间（D）-确定HIV感染的传染阶段持续时间如何与风险行为和抗逆转录病毒治疗时间交叉。我们将使用目标1-3的数据来开发一个随机的、基于个体的模型，以预测在最近的HIV感染期间诊断出的个体在转变为慢性感染时继发感染的数量，以及短期抗病毒治疗对减少传播的潜在影响。项目1依赖于临床和标本核心收集的特征良好的临床数据和标本，以及项目2中传播相关性的后续测量。在项目1中收集的有助于艾滋病毒传播的流行病学数据将有助于确定项目2中艾滋病毒传播的相关因素。行政核心将协调对项目1和2的行政、财政、数据和统计支助。这些数据将提供关键信息，艾滋病毒传播的流行病学决定因素，在艾滋病毒-1亚型B占主导地位，这是缺乏男男性行为者，并将产生重要的探索性数据，为其他人群。

DESCRIPTION (provided by applicant): Effective prevention strategies for HIV are critically needed, and an effective HIV vaccine is the best long-range hope to dramatically reduce the rate of new HIV infections. To this goal, our current understanding of the biology and epidemiology of HIV transmission remains limited. This Program Project will focus on the identification and systematic evaluation of individuals who have been recently infected with HIV and the sexual partners who transmitted HIV to them (Transmission Pairs) to elucidate and quantify epidemiologic, behavioral, biologic, virologic, and host factors that contribute to transmission. The San Diego Primary Infection research group has a long and successful history of recruiting acutely and very recently HIV-infected individuals and their transmitting partners. With new approaches to expand our identification of such study participants, as described in the Clinical and Specimen Core, we will address in Project 1 (Transmission Probability): (Aim 1) the transmission probability per contact ((J), (Aim 2) the rate of partner change (c), (Aim 3) the duration of infectious stages (D), and thus determine the reproductive number (R0) of HIV in this population. These investigations will be complemented with Project 2 (Transmission Correlates) that will identify and quantify the contributions of important biologic (Aim 1), viral (Aim 2), and host (Aim 3) correlates of HIV sexual transmission. Most importantly, this research will allow for the accurate estimation of a potential prevention strategy or candidate vaccine's anticipated efficacy based on both an estimation of the target populations' ongoing risk behavior and a thorough understanding of viral and host factors that contribute to HIV transmission. The Administrative Core (Core A) will play a central role in coordinating the administrative, fiscal, data, and statistical support for this Project as well as providing scientific support and facilitating synergistic interaction among investigators and collaborators critical to the success of the interactive projects. The Clinical and Specimen Core (Core B) will identify, recruit and enroll study subjects and collect, process, store, and manage the clinical specimens needed to meet the objectives of the two proposed research projects. PROJECT 1: Transmission Probability (Strathdee, S.) PROJECT 1 DESCRIPTION (provided by applicant): Modeling prevention interventions requires insights into epidemiological and biological factors affecting HIV transmission. Project 1 of the proposed Program Project addresses the epidemiological determinants of HIV transmission by examining the per contact transmission probability (P), the rate of partner change/ contact rate (c), and the duration of infectiousness (D), which all contribute to the reproductive number (R0= pcD), defined as the average number of secondary infections arising from a single infection in a completely susceptible population. To achieve this objective, we will address the following specific aims: Aim 1: Per contact transmission probability (P) - The per contact sexual transmission probability of HIV will be estimated, taking into account stage of HIV infection in the source partner, presence of viral and bacterial sexually transmitted infections, circumcision status, and other biological cofactors investigated in Project 2. The absolute and relative difference of transmission probability for insertive versus receptive anal sex will also be considered. Aim 2: Rate of partner change (c) - The role of partner selection in HIV acquisition and transmission risk will be examined at individual, partnership, and network levels. At the individual level, the relative contribution of HIV risk due to number of sexual acts versus number of sexual partners will be examined. At the partnership level, risk characteristics will be compared between transmitting and seroconcordant non-transmitting partnerships. At the network level, risk of acquisition and transmission of HIV based on the location of individuals within networks of venues used to meet sex partners, and correlates of being in a transmission cluster, will be elucidated. Aim 3: Duration of infectiousness (D) - To determine how duration of the infectious stages of HIV infection intersects with risk behaviors and time to antiretroviral treatment. We will use data from Aims 1-3 to develop a stochastic, individual-based model to predict the number of secondary infections arising from individuals diagnosed during recent HIV infection as they transit to chronic infection, and the potential impact of short-course antiviral therapy on reducing transmission. Project 1 depends on well-characterized clinical data and specimens collected by the Clinical and Specimen Core and the subsequent measurement of transmission correlates in Project 2. Epidemiological data contributing to HIV transmission collected in Project 1 will help to define correlates of HIV transmission in Project 2. The Administrative Core will coordinate administrative, fiscal, data, and statistical support for Projects 1 and 2. These data will provide critical information on epidemiological determinants of HIV transmission in a setting where HIV-1 subtype B predominates, which are lacking for MSM, and will generate important exploratory data for other populations.