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

项目摘要 暴露前预防（PrEP）在个人层面上起作用，以防止艾滋病毒感染，目前正在 在全球范围内向艾滋病毒感染高危人群推广，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，需要人口水平的指标来了解PrEP交付计划是否有效地实现艾滋病毒 预防对于抗逆转录病毒治疗（ART），社区病毒载量提供了深入了解传染性。同样地， 社区PrEP使用和艾滋病毒风险的措施可以为PrEP提供洞察力，并确定客户的差距 外展和坚持支持。在这个R21应用程序中，我们将开发第一个“社区”模型 替诺福韦水平”。我们将在现有的艾滋病毒传播模型（包括艾滋病毒发病率、抗逆转录病毒疗法 摄取、病毒抑制以及PrEP依从性和HIV风险的假设），并利用客观PrEP 一项对350名年轻女性进行的队列研究的依从性数据和艾滋病毒风险的多重评估 在肯尼亚采取PrEP，称为MPYA（在年轻成年女性中监测PrEP）。我们提出以下目标： 1.测量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队列。目前，资金可用于15%的参与者访问随机抽样。我们建议 分析额外的500个DBS，这将使PrEP使用第一年的特征更加完整。 2.调整现有的HIV传播模型，利用社区替诺福韦水平和HIV风险的异质性， 估计PrEP对撒哈拉以南非洲年轻女性艾滋病毒感染的影响。 2a.基于我们目前的艾滋病毒传播模型，我们将增加DBS TFV-DP水平（目标1）加上性传播， 从MPYA组群的行为来估计“有效的社区替诺福韦水平”（即，的比例 tenofovir保护的无避孕套性行为）。这项工作将涉及我们的艾滋病毒参数化 传播模型和验证数据来自其他三项研究的准备在年轻的非洲妇女。 2b.使用新的PrEP影响模型（Aim 2a）估计社区中所需的替诺福韦水平， 按年龄和风险群体分列的年轻妇女，以减少个人和人口一级的艾滋病毒发病率。 该提案的研究人员包括PrEP依从性（Haberer博士）和HIV领域的领导者 建模（Barnabas博士）与PrEP交付专家（Irungu博士）的关键上下文输入。这项建议 反映了一种新的方法，人口水平的依从性估计，可以提供急需的指导 在撒哈拉以南非洲推广PrEP。它建立和扩展在坚实的科学前提下的研究 显示坚持PrEP有效性的重要性，以及人口水平的潜力 来自客观生物标志物的信息。因此，该提案的产品具有很大的潜力， 科学和推动PrEP实施研究领域的前进。

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.