The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.

中文翻译：

---

BKEVER 试验的见解：比较依维莫司与吗替麦考酚酯治疗肾移植受者 BK 多瘤病毒感染


MTOR 抑制剂已证明具有抗病毒特性，先前的非随机研究表明它们可能对 BKPyV 复制具有抑制作用。在这里，在这项随机、多中心、对照试验 （BKEVER 研究） 中，我们试图评估依维莫司 （EVR） 与简单地减少肾移植受者 （KTR） 的免疫抑制相比，在促进 BKPyV 清除方面的影响。总共将 130 例患有 BKPyV DNA 血症的 KTR 以 1：1 的比例随机分为两组。EVR 组，其中吗替麦考酚酯 （MMF） 被 EVR 取代，钙调磷酸酶抑制剂谷水平降低，其次是 MMF 组，其中 MMF 剂量减少了一半，钙调磷酸酶抑制剂水平也降低了。主要终点是在 6 个月时达到病毒清除的患者比例。次要终点包括 BKPyV 随时间复制的动力学、BKPyV 相关肾病的发生率、肾移植功能、肾移植物排斥反应的发生率和两年内的药物耐受性。值得注意的是，EVR 组 55.7% 的患者在 6 个月时实现了 BKPyV 清除，而 MMF 组为 81.3%。MMF 组 BKPyV DNA 载量的降低明显更快。钙调神经磷酸酶抑制剂谷水平在预期目标范围内，从随机分组到第 6 个月，两组之间没有显著差异。2 例移植物丢失，4 例患者死亡。EVR 组 11 例患者和 MMF 组 6 例患者发生活检证实的 BKPyV 肾病。 因此，在患有 BKPyV DNA 血症的 KTR 中，用 EVR 代替 MMF 并降低钙调磷酸酶抑制剂水平不会导致更频繁或更快地清除 BKPyV。