Department of Infectious Diseases and Department of Nephrology, University Duisburg-Essen, Essen, Germany.
Transplantation Center, Medical Clinic I, University Hospital Schleswig-Holstein, Luebeck, Germany.
Transplantation. 2018 May;102(5):876-882. doi: 10.1097/TP.0000000000002024.
The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome in cytomegalovirus (CMV)-positive (R+) renal transplant recipients.
Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater (polymerase chain reaction) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (donor CMV IgG positive [D+]/R+, donor CMV IgG negative [D-]/R+).
The 12-month results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 (11.5%; 95% confidence interval [95% CI], 6.8-17.8%] vs 39.7%; 95% CI, 31.9-48.0%; P < 0.0001 and 4.7%; 95% CI, 1.9-9.5% vs 15.9%; 95% CI, 10.5-22.7%; P = 0.002). Incidences of graft loss (7.4% vs 8.6%), death (9.5% vs 11.3%), rejection (29.1% vs 28.5%), and renal function (estimated glomerular filtration rate [mean ± SD]: 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups.
Prophylaxis was more effective than the preemptive approach, applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients. Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment.
VIPP 研究比较了更昔洛韦预防与抢先治疗在 CMV（巨细胞病毒）阳性（R+）肾移植受者中的疗效、安全性和长期移植物结局。
这是一项多中心、开放标签、随机临床试验，研究阶段为 12 个月，随访时间长达 84 个月。预防组患者接受调整肾功能后的 2×450mg/d 口服缬更昔洛韦治疗 100 天。病毒载量为 400CMV 拷贝/mL 或更高时（聚合酶链反应）开始 2×900mg/d 缬更昔洛韦抢先治疗，并持续至少 14 天，随后进行二级预防。根据供体 CMV IgG 血清状态（供体 CMV IgG 阳性 [D+]/R+、供体 CMV IgG 阴性 [D-]/R+）对患者进行分层。
12 个月的结果之前已经报告（Witzke 等人，移植 2012 年）。意向治疗/安全性人群包括预防组 148 例（61.5% D+/R+）和抢先治疗组 151 例（52.3% D+/R+）患者。总体而言，47%的患者完成了随访。与抢先治疗组相比，预防组至第 84 个月时发生 CMV 感染或疾病的患者明显更少（11.5%；95%置信区间[95%CI]，6.8-17.8%）vs 39.7%；95%CI，31.9-48.0%；P<0.0001 和 4.7%；95%CI，1.9-9.5%）vs 15.9%；95%CI，10.5-22.7%；P=0.002）。移植物丢失（7.4% vs 8.6%）、死亡（9.5% vs 11.3%）、排斥（29.1% vs 28.5%）和肾功能（估计肾小球滤过率[平均值±标准差]：58.2±26.3 vs 59.9±25.7mL/min/1.73m）在预防组和抢先治疗组之间无显著差异。两组的耐受性相当。
与抢先治疗相比，预防策略更有效，通过采用低强度监测方案，在预防中等风险患者的 CMV 感染和疾病方面更有效。在本长期试验中，启动抗 CMV 治疗的阈值为 400 拷贝/mL，两种策略在预防移植物丢失和死亡方面同样有效。
