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

乌干达的Rakai地区是东非艾滋病毒流行的最初中心，现在仍然是一个 艾滋病毒感染率约为13%的高负担地区。通过开放的、基于人口的Rakai社区， 队列研究（RCCS），我们报告说，联合艾滋病毒预防（CHP）减少人口水平的艾滋病毒 Rakai的发病率从CHP扩大前的1.17/100人-年（pys）下降42%，到2016年下降到0.66/100 pys （Grabowski et al. NEJM 2017）。这项研究的影响和局限性提出了两个全球性问题， 重要性首先，移动的人，通常是外出工作或上学的人，很少有拒绝者，是“难以接触”的人。 这使得RCCS的参与率降至约62%。这些人群可能 同样难以接触到艾滋病毒服务。正在进行的艾滋病毒预防随机分组试验 基于人口的艾滋病毒影响评估也面临类似的挑战， 难以接触的人群。第二，尽管男性包皮环切覆盖率达到59%， 在RCCS中，所有HIV阳性参与者的病毒抑制率达到75%的目标， 中度，并且仍然远高于HIV消除所需的估计速率（约0.1/100 py）。解决 艾滋病病毒在Rakai地区持续传播，RCCS所在的PEPFAR计划最近开始实施 实施额外的卫生防护中心干预措施：（i）暴露前预防;（ii）协助伴侣 通知;和（三）当天抗逆转录病毒治疗。这种环境提供了一个独特的机会， 解决以下重要问题：（1）难以接触的人群在多大程度上影响艾滋病毒覆盖率 和发病率估计？(2)为什么有些人继续感染艾滋病毒，从谁那里感染？(3)给定 难以接触到的人群，最先进的卫生防护中心能否在规划环境中将艾滋病毒发病率降低到 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能够回答这些问题 这些研究将为当前和未来的艾滋病预防试验、评估和项目提供信息。我们 因此，提出了一个新的研究与以下目的。目标1-我们会先确定卫生防护中心的覆盖率及爱滋病病毒的感染率 使用强化监测技术，提高难以接触到的人群的发病率。目标2-我们将 通过伴侣追踪、病毒遗传学和性行为来描述正在发生的艾滋病毒感染源。 网络分析。目标3-最后，我们将确定最先进的热电联产是否可以从事难以达到的 这将有助于减少人口中的艾滋病毒感染率，并将人口一级的艾滋病毒感染率降低到足以在2030年前消除艾滋病毒的水平。对我们 知识，没有以前的艾滋病毒基于人群的研究经验确定的潜在影响， 由于不包括难以接触到的人群，对艾滋病毒流行病学和发病率的参与偏见。这 这项研究将独特地解决难以接触到的人群的问题，这些问题对于了解真正的 流行病的状态，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.