Hard-to-Reach Populations: Implications for Ending the AIDS Epidemic

乌干达的拉凯地区是东非艾滋病毒流行的最初震中，目前仍是 高负担地区，艾滋病毒流行率约为13%。通过开放、以人口为基础的Rakai社区 队列研究(RCCS)，我们报告了艾滋病毒联合预防(CHP)降低了人群水平的艾滋病毒 Rakai的发病率从CHP规模之前的1.17/100人年(Pys)下降了42%-到2016年达到0.66/100人年(Pys) (Grabowski等人)NEJM 2017)。这项研究的影响和局限性提出了两个全球 重要性。首先，流动人口，通常是外出工作或上学的人，以及很少拒绝的人是一个“难以接触到的人” 难以调查的人口，使农村信用社参与率降至约62%。这些人群可能 同样，很难接触到参与艾滋病毒服务的人。正在进行的整群随机HIV预防试验 而基于人群的艾滋病毒影响评估也面临着类似的挑战，即由于遗漏了这些 难以接触到的人群。第二，尽管男性包皮环切率达到59%，联合国艾滋病规划署达到90-90-90 目标：RCC中所有艾滋病毒阳性参与者的病毒抑制率达到75%，艾滋病毒发病率下降 中等，并保持在远高于估计的消除艾滋病毒所需的速度(约0.1/100年)。致信地址 在Rakai地区持续的艾滋病毒传播，农村合作伙伴所在的PEPFAR方案最近开始 实施额外的卫生防护方案干预措施：(I)暴露前预防(PrEP)；(Ii)受助性伙伴 通知；和(3)当日抗逆转录病毒治疗(ART)。这种环境提供了一个独特的机会 解决以下重要问题：(1)难以接触到的人群在多大程度上偏向艾滋病毒覆盖率 和发病率估计？(2)为什么一些人继续感染艾滋病毒？从谁那里感染？(3)给予 在难以接触到的人群中，最先进的卫生防护方案能否在规划环境中降低艾滋病毒的发病率 消除艾滋病毒所需的水平？我们的环境和研究基础设施使我们有能力回答这些问题 非常重要的问题，并为当前和未来的艾滋病毒预防试验、评估和计划提供信息。我们 因此，提出了一项具有以下目的的新颖研究。目标1-我们将首先确定卫生防护方案的覆盖率和艾滋病毒 使用强化监测技术的难以接触人群中的发病率。目标2--我们会 通过伴侣追踪、病毒系统发育和性行为描述持续的HIV感染来源 网络分析。目标3-最后，我们将确定最先进的卫生防护中心是否能够接触到难以接触到的 并在2030年之前将人口层面的艾滋病毒发病率降低到足以消除艾滋病毒的水平。致我们的 知识，之前没有任何基于艾滋病毒人群的研究经验地确定了 由于没有纳入难以接触到的人群，对艾滋病毒流行病学和发病率的参与偏向。这 这项研究将独特地解决难以接触到的人群的问题，这些问题对于理解真相至关重要 流行病状况，解释艾滋病毒预防试验和横断面研究，并告知前景 以及结束非洲艾滋病毒流行的途径。

The Rakai region in Uganda was the initial epicenter of the HIV epidemic in East Africa and continues to be a high burden area with an HIV prevalence of ~13%. Through the open, population-based Rakai Community Cohort Study (RCCS), we reported that combination HIV prevention (CHP) decreased population-level HIV incidence in Rakai by 42% from 1.17/100 person-years (pys) prior to CHP scale-up to 0.66/100 pys by 2016 (Grabowski et al. NEJM 2017). Implications and limitations from this study raise two issues of global importance. First, mobile persons, typically away for work or school, and, rarely, refusers are a “hard-to-reach” population that is difficult to survey, reducing RCCS participation rates to ~62%. These populations may likewise be hard-to-reach for engagement in HIV services. Ongoing cluster-randomized HIV prevention trials and population-based HIV impact assessments have similar challenges of potential bias due to missing these hard-to-reach populations. Second, despite reaching 59% male circumcision coverage and UNAIDS 90-90-90 goals with 75% viral suppression of all HIV-positive participants in RCCS, HIV incidence reductions were moderate and remained well above the estimated rate needed for HIV elimination (~0.1/100py). To address ongoing HIV transmission in the Rakai region, the PEPFAR program in which RCCS is nested recently began implementing additional CHP interventions: (i) Pre-Exposure Prophylaxis (PrEP); (ii) assisted Partner Notification; and (iii) Same-day antiretroviral therapy (ART). This environment provides a unique opportunity to address the following important questions: (1) To what extent do hard-to-reach populations bias HIV coverage and incidence estimates? (2) Why do some individuals continue to acquire HIV and from whom? (3) Given hard-to-reach populations, can state-of-the-art CHP in a programmatic setting reduce HIV incidence to the levels needed for HIV elimination? Our setting and research infrastructure strongly position us to answer these highly significant questions and inform current and future HIV prevention trials, evaluations, and programs. We thus propose a novel study with the following Aims. Aim 1-We will first determine CHP coverage and HIV incidence among hard-to-reach persons using enhanced surveillance techniques. Aim 2-We will then characterize ongoing sources of incident HIV infection through partner tracing, viral phylogenetics, and sexual network analyses. Aim 3-Finally, we will determine if state-of-the-art CHP can engage hard-to-reach populations and reduce population-level HIV incidence to a level sufficient for HIV elimination by 2030. To our knowledge, no prior HIV population-based studies have empirically determined the potential effects of participation bias on HIV epidemiology and incidence due to non-inclusion of hard-to-reach populations. This study will uniquely address questions on hard-to-reach populations which are critical to understanding the true state of the epidemic, interpreting HIV prevention trials and cross-sectional studies, and informing prospects and pathways to ending the African HIV epidemic.