1 Departments of Transplant Surgery and Pharmacy Services, and the Renal Division, Brigham and Women's Hospital, Boston, MA. 2 Harvard Medical School, Boston, MA. 3 Department of Pharmacy Services, Beth Israel Deaconess Medical Center, Boston, MA. 4 Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI. 5 Department of Pharmacy Services, University of California San Diego Medical Center, San Diego, CA. 6 Department of Transplant Surgery and Pharmacy Services, Tufts Medical Center, Boston, MA. 7 Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA. 8 Department of Pharmacy Services, Yale New Haven Hospital, New Haven, CT. 9 Department of Pharmacy Services, University of California Irvine Medical Center, Orange, CA. 10 Department of Pharmacy Services, Massachusetts General Hospital, Boston, MA.
Transplantation. 2015 Jul;99(7):1499-505. doi: 10.1097/TP.0000000000000570.
Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR).
Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed.
Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar.
Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.
尽管更昔洛韦 900mg/天的长期巨细胞病毒（CMV）预防方案已被证实有效，但由于报告的成功和成本节约，一些中心使用 450mg/天的剂量。这项多中心、回顾性研究比较了高危、供体阳性/受者阴性、肾移植受者（RTR）接受 6 个月低剂量和高剂量缬更昔洛韦预防的疗效和安全性。
对 237 例高危 RTR（低剂量组=缬更昔洛韦 450mg/天[n=130]；高剂量组=缬更昔洛韦 900mg/天[n=77]）进行了为期 1 年的 CMV 疾病流行率评估。突破性 CMV、耐药性 CMV、活检证实的急性排斥反应（BPAR）、移植物丢失、机会性感染（OI）、移植后新发糖尿病（NODAT）、过早停止使用缬更昔洛韦、肾功能和骨髓抑制也进行了评估。
患者的人口统计学和移植特征相似。诱导和维持免疫抑制相似，但高剂量组早期类固醇停药更多。CMV 疾病的发生比例相似（14.6%vs24.3%；P=0.068）；然而，通过多变量逻辑回归控制 CMV 危险因素差异后，低剂量组的 CMV 疾病发生率显著降低（P=0.02；比值比，0.432，95%置信区间，0.211-0.887）。突破性和耐药性 CMV 的发生频率相似。肾功能或活检证实的急性排斥反应、移植物丢失、机会性感染或移植后新发糖尿病的发生率无差异。高剂量组在第 5 和 6 个月时的平均白细胞计数明显较低；然而，过早停止使用缬更昔洛韦的发生率相似。
低剂量和高剂量缬更昔洛韦方案在预防高危 RTR 的 CMV 疾病方面具有相似的疗效，低剂量方案与白细胞减少症的发生率降低相关，而耐药性 CMV 无差异。低剂量缬更昔洛韦可能带来显著的成本节约效益。
