A Multi-site Multi-Setting RCT of Integrated HIV Prevention and HCV Care for PWID

摘要 北美的阿片类药物危机带来了一系列健康后果，包括艾滋病毒和肝炎 丙型肝炎病毒暴发。艾滋病毒和丙型肝炎病毒是注射者发病率和死亡率的主要贡献者 药物(PWID)。这些感染还承担着巨大的医疗费用。虽然艾滋病毒治疗的规模仍在扩大 需要对艾滋病毒和丙型肝炎病毒的预防和护理进行必要的重大改进，以大幅减少 PWID人群中HIV和丙型肝炎的负担。暴露前预防(PrEP)和丙型肝炎治愈方案有 减少这两种同时发生的流行病的变革性潜力。实施的一个关键问题 研究是如何最好地将这些药理进展整合到PWID的预防和护理策略中。 鉴于先前在PWID中对PrEP的研究相对匮乏，我们迫切需要扩大我们的 了解PrEP对参与丙型肝炎评估和治疗的PWID的潜在作用。在这个范围内 在此背景下，我们提出了一个随机的混合有效性-实施试验(n=500)来评估两个 PWID中PrEP和丙型肝炎综合护理的实施策略：现场综合护理(PrEP) 启动和丙型肝炎病毒治疗)与异地转诊，患者导航到专门护理。HIV阴性的PWID 将从两个地点招募-阿片类药物替代治疗(OST)地点和注射器交换计划 (SEPS)-在两个北美城市-迈阿密和蒙特雷亚尔。这些城市提供了背景的可变性 医疗服务(蒙特利尔-高服务/低障碍与迈阿密-低服务/高障碍)；场馆 提供开销/资源的可变性(OTP-高资源与SEPS-低资源)。有两个 总体目标：1)确定PrEP和丙型肝炎病毒综合治疗是否在现场提供治疗和危害 减少设置导致更高的a)持续的PrEP依从率和/或b)丙型肝炎病毒治愈(初级 结果)，与具有患者导航的异地转诊进行比较，以及c)测试本地 环境和场地对主要结果的影响，以及2)评估a)卫生保健利用的影响和 现场综合护理方法与患者导航器转诊的相对资源使用情况比较 方法和b)在当地扩大这些干预方法所需的保健资源 环境和设置。次要结果将包括PrEP的启动、使用、长期持续PrEP 依从性、丙型肝炎病毒治疗开始、危险行为改变、丙型肝炎病毒感染/再感染以及性传播疾病/艾滋病毒发病率。 对于这些次要结果，我们还将包括一项定性研究，以了解 可能与PrEP遵守和问题相关的个人、人际和社会背景因素 随着时间的推移，PWID的行为补偿。其他定性研究将检查促进者和 实施的障碍。这个由两个城市和两个场馆组成的设计将提供重要的信息来理解 在高资源和低资源地理环境以及高资源和低资源地理环境中的执行/传播问题 头顶上的场地。

Abstract The opioid crisis in North America comes with a multitude of health consequences, including HIV and Hepatitis C (HCV) outbreaks. HIV and HCV are major contributors to morbidity and mortality among persons who inject drugs (PWID). These infections also bear significant medical costs. While HIV treatment scale-up remains essential, significant improvements in HIV and HCV prevention and care are required to reduce substantially the HIV and HCV burden among PWID. Pre-exposure prophylaxis (PrEP) and the HCV cure regimens have transformative potential to reduce these two co-occurring epidemics. A key question for implementation research is how to best integrate these pharmacological advances in prevention and care strategies for PWID. Given the relative dearth of prior research on PrEP among PWID, we critically need to expand our understanding of the potential role of PrEP for PWID engaged in HCV assessment and treatment. Within this context, we propose a randomized hybrid effectiveness-implementation trial (n=500) to evaluate two implementation strategies for PrEP and HCV care integration among PWID: on-site integrated care (PrEP initiation and HCV treatment) vs. off-site referral with patient navigation to specialized care. HIV-negative PWID will be recruited from two venues—opioid substitution therapy (OST) venues and syringe exchange programs (SEPs)—within two North American cities—Miami and Montréal. The cities provide variability in background health access (Montreal-High Services/Low Barriers versus Miami-Low Services/High Barriers); venues provide variability in overhead/resources (OTPs-High Resources versus SEPs-Low Resource). There are two overall aims: 1) To determine if integrated PrEP and HCV treatment offered on-site in treatment and harm reduction settings results in higher rates of a) sustained PrEP adherence and/or b) HCV cure (primary outcomes), compared to an off-site referral with patient navigation, and to c) test the contributions of local environment and venue on primary outcomes, and 2) To evaluate a) the health care utilization impact and the relative resource use of the on-site integrated care approach compared to the referral with patient navigator approach and b) the health care resources required to scale up these intervention approaches in the local environments and settings. Secondary outcomes will include PrEP initiation, use, long-term sustained PrEP adherence, HCV treatment initiation, risk behavior changes, HCV infection/reinfection, and STD/HIV incidence. For these secondary outcomes, we also will include a qualitative study to understand the interplay of the personal, interpersonal, and social contextual factors that may be associated with PrEP adherence and issues of behavioral compensation over time for PWID. Additional qualitative study will examine facilitators and barriers to implementation. This two-city by two-venue design will provide crucial information to understand implementation/dissemination issues in both high and low resource geographic contexts and high and low overhead venues.