The Landscape of Serious Infections following Kidney Transplantation in People Living with HIV

项目摘要/摘要 肾移植(KT)是对10,000名艾滋病毒携带者(PLWH)的挽救生命的干预措施。 在美国，肾脏疾病处于发展阶段。这种做法在21世纪初被证实是安全有效的，已经 在过去十年中，随着针对艾滋病毒和丙型肝炎(丙型肝炎)的变革性抗病毒技术的进步， 以及通过允许艾滋病毒对艾滋病毒进行移植的艾滋病毒器官政策公平(HOPE)法案。尽管 这一弱势群体的复杂性质，既不是严重感染的情况，也不是对 已经确定了平衡感染和肾脏排斥风险的最佳免疫抑制的范围。这是至关重要的 将这一范例理解为感染导致KT和排斥反应后20%的早期死亡，这导致 免疫抑制增强和更易受感染的宿主在HIV+KT中常见2-4倍 收件人。 这项提案的目标包括描述以下严重感染的负担、时间和范围 HIV+KT与匹配的HIV-KT接受者的比较，以了解与以下疾病相关的不同风险 接受者艾滋病毒状况(目标1)。这将通过发展最大的艾滋病毒+KT队列来实现 通过将移植受者科学登记处和美国肾脏数据系统联系起来， 它还纳入了医疗保险中心和医疗补助索赔数据，以确定严重感染事件。 下一步，将在艾滋病毒+KT接受者中进行风险因素分析，重点是 与发生移植后严重并发症相关的生物学变量和免疫抑制方案 感染(目标2)。此分析的目标是为有针对性的监测和预防提供信息，以防止 HIV+KT受者的感染并发症。最后，捐赠者的艾滋病毒状况与严重的 将通过正在进行的希望在行动多中心的强大基础设施来探索感染风险 这项分析将纳入关于HIV+器官的丰富数据 捐赠者和接受者，包括迄今未探索的艾滋病毒生物学和实验室标记物 强大的感染和排斥报告。 综上所述，这项建议旨在勾勒出严重感染公共卫生署辖下医院的情况。 KT在现代使用全面的感染查明方案和严格的流行病学 方法：研究方法。最终，我们的目标是促进对这一独特和 新兴群体并推动循证实践，以改善KT后的长期结果。

Project Summary/Abstract Kidney transplantation (KT) is a lifesaving intervention for the 10,000 people living with HIV (PLWH) and end- stage renal disease in the United States. Confirmed as safe and effective in the early 2000s, this practice has rapidly expanded in the past decade amid transformative antiviral advances for HIV and hepatitis C (HCV) as well as passage of the HIV Organ Policy Equity (HOPE) Act permitting HIV-to-HIV transplantation. Despite the complex nature of this vulnerable population, neither the landscape of serious infections nor an understanding of optimal immunosuppression to balance infection and kidney rejection risk has been defined. It is critical to understand this paradigm as infection causes >20% of early deaths following KT and rejection, which results in immunosuppressive intensification and a more susceptible host, is 2-4-fold more common in HIV+ KT recipients. The goals of this proposal include characterizing the burden, timing, and spectrum of serious infections after HIV+ KT with comparison to matched HIV- KT recipients to understand differential risks associated with recipient HIV status (Aim 1). This will be accomplished through development of the largest cohort of HIV+ KT recipients to date by linking the Scientific Registry of Transplant Recipients and the US Renal Data System, which also incorporates Centers for Medicare and Medicaid claims data to ascertain serious infection events. Pharmacy clearinghouse data will augment infection, rejection, and antimicrobial prophylaxis ascertainment. Next, among the population of HIV+ KT recipients, a risk factor analysis will be performed with focus on biological variables and immunosuppressive regimens associated with developing serious post-transplant infections (Aim 2). The goal of this analysis is to inform targeted monitoring and prophylaxis to prevent infectious complications in HIV+ KT recipients. Finally, the association of donor HIV status with serious infection risk will be explored through the robust infrastructure of the ongoing HOPE in Action multicenter clinical trials of HIV-to-HIV KT (NCT03500315, Aim 3). This analysis will incorporate rich data on HIV+ organ donors and recipients including hitherto unexplored HIV biology and laboratory markers, in the context of robust infection and rejection reporting. Taken together, this proposal seeks to delineate the landscape of serious infection among PLWH undergoing KT in the modern era using a comprehensive infection ascertainment schema and rigorous epidemiologic methods. Ultimately, the goal is to advance understanding of infectious complications in this unique and emerging group and drive evidence-based practices that improve long-term post-KT outcomes.