Section of Nephrology, Medical Department, Oslo University Hospital, Oslo, Norway.
Transplantation. 2011 Jul 27;92(2):217-23. doi: 10.1097/TP.0b013e31821fad25.
Cytomegalovirus (CMV) infections in kidney transplant recipients are in most cases successfully treated with oral valganciclovir (VGCV). However, in a few percent of patients, mutations in the UL 97 or UL 54 gene lead to drug resistance.
We investigated the incidence and outcomes of ganciclovir-resistant CMV viremia in all 1244 kidney recipients transplanted at our center from 2004 through 2008. CMV DNAemia was monitored in all patients at least weekly, and patients who were positive were treated preemptively with VGCV (900 mg once daily).
Ganciclovir-resistant mutations were detected in 27 patients (2.2%), of which 26 occurred in the 209 CMV IgG-negative recipients receiving a CMV-positive kidney (12.5%). All had UL97 gene mutations, and none had UL54 gene mutations. Mean DNAemia half-life for the first (nonresistance) episode of CMV viremia was 3.8 ± 1.2 days. After established resistance, 25 of 27 patients had their mycophenolate mofetil dose reduced by approximately 50%, and 10 of these were also treated with intravenous foscarnet. The DNAemia half-life was 3.7 ± 1.4 days in the foscarnet-treated patients, significantly shorter than in the other 17 patients, 10.8 ± 6.7 days (P = 0.001). Time to DNAemia eradication was 30 ± 16 and 81 ± 51 days in the two groups, respectively (P = 0.001).
Use of 900 mg VGCV once daily for preemptive CMV treatment is associated with a high incidence of CMV UL97-resistance gene mutations in D+/R- patients. Foscarnet treatment rapidly and safely eradicated CMV DNAemia, and also patients who only reduced the immunosuppression and continued on VGCV treatment eventually cleared the virus.
巨细胞病毒（CMV）感染在大多数情况下可通过口服缬更昔洛韦（VGCV）成功治疗。然而，在少数患者中，UL97 或 UL54 基因的突变导致药物耐药。
我们调查了 2004 年至 2008 年期间在我们中心接受移植的 1244 名肾移植患者中所有出现更昔洛韦耐药性 CMV 血症的发生率和结果。所有患者至少每周监测 CMV DNA 血症，阳性患者用 VGCV（900mg，每天一次）进行预防性治疗。
在 27 例患者（2.2%）中检测到更昔洛韦耐药性突变，其中 26 例发生在 209 例 CMV IgG 阴性接受 CMV 阳性供肾的患者中（12.5%）。所有患者均发生 UL97 基因突变，无一例发生 UL54 基因突变。CMV 病毒血症首次（非耐药性）发作的 DNA 血症半衰期为 3.8 ± 1.2 天。在确立耐药性后，27 例患者中有 25 例将霉酚酸酯剂量减少约 50%，其中 10 例还接受了更昔洛韦治疗。用膦甲酸酯治疗的患者 DNA 血症半衰期为 3.7 ± 1.4 天，明显短于其他 17 例患者的 10.8 ± 6.7 天（P = 0.001）。两组患者的 DNA 血症清除时间分别为 30 ± 16 天和 81 ± 51 天（P = 0.001）。
每日口服 900mg VGCV 进行预防性 CMV 治疗与 D+/R-患者中 CMV UL97 耐药基因突变的高发生率有关。膦甲酸酯治疗可迅速、安全地消除 CMV DNA 血症，且仅降低免疫抑制并继续用 VGCV 治疗的患者最终也可清除病毒。
