PREVINE-TB: PRevent: EValuating the implementation of NEw strategies for preventive TB among people living with HIV in Brazil

项目总结 尽管结核病是一种可预防和可治疗的疾病，但每年导致略低于200万人死亡， 脆弱人群，特别是艾滋病毒携带者(PLWH)，患病风险最高， 死亡。在巴西，PLWH的结核病发病率明显较高，PLWH预防结核病是当务之急。然而， 我们先前在里约热内卢的工作估计，每年只有12%的符合条件的PLWH接受结核病预防治疗 并确定了在PLWH中提供有效的结核病预防治疗的两个关键制约因素：结核菌素 潜伏性结核病感染(LTBI)的皮肤测试(TST)和坚持6个月的异烟肼预防治疗 (IPT)。有了QFT+，第4代干扰素伽玛释放试验，LTBI状态可以作为 患者无需返回诊所即可常规抽血。这一战略有可能 大大改善结核病/艾滋病毒预防的连续体。预防结核病(预防：评估 在巴西艾滋病毒携带者中实施预防结核病的新战略)将进行测试 使用QFT+和比较遵守策略优化结核病预防的实施 巴西艾滋病毒诊所的连续体。从每天服用异烟肼改为新的3HP方案(每周一次，用于 12周)，现在由疾病预防控制中心推荐，可能会提高患者的依从性，但也可能是 不是日常生活的一部分。3HP方案最近被添加到PLWH指南中作为 巴西为期6个月的IPT课程的替代方案，但实施3HP的最佳方法尚未确定 下定决心。在以下情况下，PREVINE-TB有可能增加这些高危人群的感染率 PLWH已被证明(由我们的团队)从预防性治疗中显著受益。我们的目标是评估 巴西国家结核病方案(NTP)实施了一项新战略，以 在巴西公共卫生部门预防结核病。目标1将重点放在QFT+，作为增加LTBI AS筛查的战略 这是PLWH常规护理的一部分。我们将确定与常规病毒相关的QFT+的有效性和成本 负荷和CD4吸血，以优化结核病/艾滋病毒预防护理连续体。目标2将决定 优化患者对3HP依从性的三种可扩展方法的有效性和成本效益。我们 将对有资格参加3HP的PLWH进行一项单独随机的非劣势试验，以进行比较 基于临床的直接观察疗法(DOT，当前的护理标准)与自我给药疗法(SAT) 通过优化的文本消息。最后，我们将利用(目标3)实施综合框架 研究(CFIR)以优化干预流程并描述成功的关键要素 实施QFT+和3HP战略，为扩大规模和维护提供信息。使用混合的方法 方法，我们将探索来自三个利益相关者群体(患者、提供者和计划)的观点 管理人员/政策制定者)，以建立和改进最佳干预实施。这项评估将会有所帮助 确保研究结果以最合适和最具成本效益的方式直接转化为政策。

PROJECT SUMMARY Despite being a preventable and treatable disease, tuberculosis (TB) kills just under 2 million people annually, and vulnerable populations, especially people living with HIV (PLWH), are at highest risk for disease and death. In Brazil, TB rates are markedly higher in PLWH and preventing TB for PLWH is a top priority. However, our prior work in Rio de Janeiro estimated only 12% of eligible PLWH receiving TB preventive therapy annually and identified two critical constraints to delivery of effective TB preventive therapy among PLWH: tuberculin skin testing (TST) for latent TB infection (LTBI) and adherence to 6 months of isoniazid preventive therapy (IPT). With QFT+, a 4th generation Interferon Gamma Release Assay, LTBI status can be determined as part of routine blood draws without the patient having to return to the clinic. This strategy has the potential to substantially improve the TB/HIV prevention continuum. PREVINE-TB (PRevent: EValuating the Implementation of NEw strategies for preventing TB among people living with HIV in Brazil) will test use of QFT+ and compare adherence strategies to optimize implementation of the TB prevention continuum in HIV clinics in Brazil. A switch from daily isoniazid to the novel 3HP regimen (once weekly for 12 weeks), now recommended by the CDC, may improve patient adherence, but may also be a challenge in not being part of a daily routine. The 3HP regimen was recently added to guidelines for PLWH as an alternative to the 6-month course of IPT in Brazil, but the best method for implementing 3HP is yet to be determined. PREVINE-TB has the potential to increase uptake for this at-risk population in a setting where PLWH have been shown (by our team) to significantly benefit from preventive therapy. Our goal is to assess the implementation by the Brazilian National Tuberculosis Program (NTP) of a novel strategy to prevent TB among PLWH in Brazil. Aim 1 will focus on QFT+ as a strategy to increase screening for LTBI as part of routine care for PLWH. We will determine the effectiveness and costs of QFT+ linked to routine viral load and CD4 blood draws to optimize the TB/HIV prevention care continuum. Aim 2 will determine effectiveness and cost-effectiveness of three scalable methods for optimizing patient adherence to 3HP. We will conduct an individually randomized non-inferiority trial of adherence for PLWH eligible for 3HP to compare clinic-based directly observed therapy (DOT, the current standard-of-care) vs self-administered therapy (SAT) with optimized text messaging. Finally, we will utilize (Aim 3) the Consolidated Framework for Implementation Research (CFIR) to optimize intervention processes and describe key elements for the successful implementation of the QFT+ and 3HP strategies to inform scale-up and maintenance. Using a mixed methods approach, we will explore perspectives from three stakeholder groups (patients, providers, and program managers/policy makers) to build and improve optimal intervention implementation. This evaluation will help ensure study results are directly translated into policy in the most appropriate and cost-effective manner.