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

项目总结/摘要 肾移植（KT）是一种挽救生命的干预措施，为10,000人艾滋病毒感染者（PLWH）和结束， 肾病综合征在美国这种做法在21世纪初被证实是安全有效的， 在过去十年中，随着艾滋病毒和丙型肝炎（HCV）的变革性抗病毒进展， 以及通过艾滋病毒器官政策公平（HOPE）法案，允许艾滋病毒到艾滋病毒移植。尽管 这一脆弱群体的复杂性质，既不是严重感染的景观，也不是对 平衡感染和肾排斥风险的最佳免疫抑制剂。至关重要 我理解这种模式，因为感染导致KT和排斥反应后>20%的早期死亡，这导致 免疫抑制强化和更易感的宿主，在HIV+ KT中常见2-4倍 受惠人士 该提案的目标包括描述严重感染的负担、时间和范围， HIV+ KT与匹配的HIV-KT接受者进行比较，以了解与 接受者的艾滋病毒状况（目标1）。这将通过开发最大的艾滋病毒+ KT队列来实现 迄今为止，通过将移植受体科学登记处和美国肾脏数据系统联系起来， 它还结合了医疗保险和医疗补助中心的索赔数据，以确定严重的感染事件。 药房信息交换数据将增加感染，排斥反应和抗菌预防措施的确定。 接下来，在HIV+ KT接受者人群中，将进行风险因素分析，重点是 与移植后发生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）。该分析的目的是为有针对性的监测和预防提供信息，以防止 HIV+ KT接受者的感染并发症。最后，献血者艾滋病毒感染状况与严重 将通过正在进行的HOPE in Action多中心的强大基础设施来探索感染风险 HIV转HIV KT的临床试验（NCT 03500315，Aim 3）。这项分析将纳入关于艾滋病毒+器官的丰富数据 供体和受体，包括迄今尚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，这项建议旨在描述艾滋病毒/艾滋病感染者中严重感染的情况， KT在现代使用全面的感染确定模式和严格的流行病学 方法.最终，我们的目标是在这个独特的， 新兴群体，并推动改善长期KT后结果的循证实践。

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.