Lowance D, Neumayer H H, Legendre C M, Squifflet J P, Kovarik J, Brennan P J, Norman D, Mendez R, Keating M R, Coggon G L, Crisp A, Lee I C
Department of Internal Medicine, Piedmont Hospital, Atlanta, GA 30367, USA.
N Engl J Med. 1999 May 13;340(19):1462-70. doi: 10.1056/NEJM199905133401903.
Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease.
A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation.
Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment-limiting. The rates of other adverse events were similar among the groups.
Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.
巨细胞病毒（CMV）疾病是器官移植的主要并发症。我们假设，用伐昔洛韦进行预防性治疗可降低CMV疾病的风险。
共有208名接受血清反应阳性供者肾脏的CMV阴性受者和408名CMV阳性受者被随机分配，在移植后90天内每天口服4次2g伐昔洛韦或安慰剂，剂量根据肾功能进行调整。主要终点是移植后前6个月经实验室确诊的CMV疾病。
伐昔洛韦治疗降低了血清反应阴性患者（P<0.001）和血清反应阳性患者（P=0.03）中CMV疾病的发生率或延迟了其发病时间。在血清反应阴性患者中，移植后90天安慰剂组CMV疾病的发生率为45%，伐昔洛韦组为3%。在血清反应阳性患者中，相应的发生率分别为6%和0%。6个月时，血清反应阴性安慰剂组受者CMV疾病的发生率为45%，血清反应阴性伐昔洛韦组受者为16%；血清反应阳性安慰剂组受者为6%，血清反应阳性伐昔洛韦组受者为1%。6个月时，血清反应阴性组中安慰剂组活检证实的急性移植物排斥率为52%，伐昔洛韦组为26%（P=0.001）。伐昔洛韦治疗还降低了CMV病毒血症和病毒尿症、单纯疱疹病毒疾病的发生率以及住院医疗资源的使用。幻觉和意识模糊在伐昔洛韦治疗中更常见，但这些事件并不严重或不影响治疗。各治疗组中其他不良事件的发生率相似。
伐昔洛韦预防性治疗是预防肾移植后CMV疾病的一种安全有效的方法。
