Community tenofovir levels as a population adherence measure to understand the impact of oral PrEP on HIV acquisition among young women in sub-Saharan Africa

项目总结 暴露前预防(PrEP)在个人层面上预防艾滋病毒感染，目前正在 在全球范围内向艾滋病毒感染的高危人群推广--特别是在 撒哈拉以南非洲的年轻女性。联合国艾滋病规划署的目标是到2020年全球有300万人接受PrEP 2020年，需要人口水平的指标来了解PrEP交付计划是否实现了有效的艾滋病毒 预防。对于抗逆转录病毒治疗(ART)，社区病毒载量提供了对传染性的洞察。同样， 社区PrEP使用和HIV风险的测量可以为PrEP的交付提供洞察力，并找出客户中的差距 外展和坚持支持。在这个R21应用程序中，我们将开发出有史以来第一个“社区”模型 替诺福韦水平“。我们将建立我们现有的艾滋病毒传播模型(包括艾滋病毒发病率、ART 摄取、病毒抑制和PrEP依从性和HIV风险的假设)并利用客观的PrEP 一项对350名年轻女性进行的队列研究中的依从性数据和艾滋病毒风险的多项评估 在肯尼亚进行PrEP，称为MPYA(青年成年妇女PrEP监测)。我们提出以下目标： 1.测量已存档和未分析的干血斑(DBS)中的替诺福韦二磷酸(TFV-DP)水平 MPYA的队列。目前可为15%随机抽样的参与者访问提供资金。我们建议 分析额外的500个DBS，以便能够更完整地描述PrEP使用的第一年。 2.调整现有的艾滋病毒传播模型，利用社区替诺福韦水平和艾滋病毒风险的异质性来 估计预防接种计划对撒哈拉以南非洲年轻女性感染艾滋病毒的影响。 2A。在我们目前艾滋病毒传播模型的基础上，我们将增加DBS TFV-DP水平(目标1)外加性 来自MPYA队列的行为，以估计“有效的社区替诺福韦水平”(即 无避孕套的性行为受替诺福韦保护)。这一努力将涉及对我们的艾滋病毒进行参数化 在非洲年轻妇女中传播PrEP的模型和数据验证。 2B。使用新的PrEP影响模型(目标2a)来估计以下项目所需的社区替诺福韦水平 按年龄和风险群体分列的年轻妇女，以降低个人和人口层面的艾滋病毒发病率。 这项提案的调查人员由遵守PrEP(哈贝勒博士)和艾滋病毒领域的领导人组成 使用PrEP交付专家(Irungu博士)的关键上下文输入进行建模(Barnabas博士)。这项建议 反映了一种新的人口水平依从性评估方法，可以提供急需的指导 用于在撒哈拉以南非洲推出PrEP。它建立在研究的坚实的科学前提之上并加以扩展 显示坚持PrEP有效性的重要性，以及在人口层面上的潜力 来自客观生物标志物的信息。因此，该提案的产品具有巨大的潜力，既可以推动 科学地推进PrEP实施研究领域的发展。

PROJECT SUMMARY Pre-exposure prophylaxis (PrEP) works at an individual-level to prevent HIV acquisition and is currently being rolled out globally to people at high risk for HIV acquisition— particularly among the high priority population of young women in sub-Saharan Africa. With the UNAIDS goal of 3 million people receiving PrEP globally by 2020, population-level metrics are needed to understand if PrEP delivery programs are achieving effective HIV prevention. For antiretroviral therapy (ART), community viral load provides insight into infectiousness. Similarly, measures of community PrEP use and HIV risk may provide insight for PrEP delivery and identify gaps in client outreach and adherence support. In this R21 application, we will develop the first ever model of “community tenofovir levels”. We will build on our existing HIV transmission model (which includes HIV incidence, ART uptake, viral suppression, and assumptions of PrEP adherence and HIV risk) and leverage objective PrEP adherence data and multiple assessments of HIV risk from an ongoing cohort study of 350 young women taking PrEP in Kenya, called MPYA (Monitoring PrEP in Young Adult women). We propose the following aims: 1. Measure tenofovir diphosphate (TFV-DP) levels in archived and unanalyzed dried blood spots (DBS) from the MPYA cohort. Funding is currently available for a 15% random sample of participant visits. We propose to analyze additional 500 DBS that will enable a more complete characterization of the first year of PrEP use. 2. Adapt an existing HIV transmission model to use heterogeneity in community tenofovir levels and HIV risk to estimate the impact of PrEP on HIV acquisition in young women in sub-Saharan Africa. 2a. Building on our current HIV transmission model, we will add DBS TFV-DP levels (Aim 1) plus sexual behavior from the MPYA cohort to estimate an “effective community tenofovir level” (i.e., the proportion of condomless sex acts protected by tenofovir). This effort will involve parameterization of our HIV transmission model and validation with data from three other studies of PrEP in young African women. 2b. Use the new PrEP impact model (Aim 2a) to estimate the community tenofovir levels needed among young women by age and risk group to decrease HIV incidence at an individual and population level. Investigators for this proposal consist of leaders in the fields of PrEP adherence (Dr. Haberer) and HIV modeling (Dr. Barnabas) with critical contextual input from a PrEP delivery expert (Dr. Irungu). This proposal reflects a novel approach to population-level adherence estimation that could provide much needed guidance for the rollout of PrEP in sub-Saharan Africa. It builds and extends on the solid scientific premise of research showing the importance of adherence in PrEP effectiveness, as well as the potential for population-level information from objective biomarkers. The products of the proposal thus have great potential to both advance science and move the field of PrEP implementation research forward.