Centre Hospitalier Universitaire de Québec and Laval University, Québec, QC, Canada G1V 4G2.
J Clin Virol. 2012 Mar;53(3):208-13. doi: 10.1016/j.jcv.2011.12.019. Epub 2012 Jan 10.
The IMPACT study was a randomized, double-blind study comparing 100 to 200 days of VGCV prophylaxis (900 mg once daily) in D+/R- kidney transplant recipients. Although extending the duration of prophylaxis resulted in a significant reduction in confirmed cytomegalovirus (CMV) disease (100-day: 36.8% vs 200-day: 16.1%(1)), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown.
To determine whether extending valganciclovir prophylaxis from 100 days to 200 days increased the incidence of ganciclovir resistance.
Genotypic analysis of CMV UL97 and UL54 was conducted on virus isolated from patients meeting the predefined resistance analysis criteria (RAC).
A greater number of patients met the RAC in the 100 day prophylaxis arm (50/163; 31%) compared to the 200 day prophylaxis arm (22/155; 14%). Sequence data were successfully generated for all 200-day patients and 48/50 100-day patients. Three patients in each treatment arm (100 day: 3/163 (1.8%) vs 200 day: 3/155 (1.9%)) had a single known valganciclovir resistance mutation detected (100 day: UL97 gene: M460V, C592G twice; 200 day: UL97 gene: C603W, M460V and UL54 gene: P522S). Overall, a resistance mutation was more likely to be detected if the patient met the RAC during prophylaxis (5/12 (42%)) compared to post-prophylaxis (1/58 (2%)). All six patients with known ganciclovir resistance mutations cleared the virus; three cleared virus without treatment and three cleared virus following treatment.
Extending valganciclovir prophylaxis from 100 days to 200 days did not significantly affect the incidence of ganciclovir resistance.
IMPACT 研究是一项随机、双盲研究，比较了 D+/R-肾移植受者使用 VGCV 预防治疗 100 至 200 天（900mg 每日一次）。尽管延长预防治疗时间可显著降低明确的巨细胞病毒（CMV）疾病发生率（100 天：36.8% vs 200 天：16.1%），但延长预防治疗时间对病毒耐药性发展的影响尚不清楚。
确定将缬更昔洛韦预防治疗时间从 100 天延长至 200 天是否会增加更昔洛韦耐药的发生率。
对符合预先设定耐药分析标准（RAC）的患者分离的病毒进行 CMV UL97 和 UL54 的基因分型分析。
100 天预防治疗组符合 RAC 的患者人数（50/163；31%）多于 200 天预防治疗组（22/155；14%）。所有 200 天患者和 50 名 100 天患者中的 48 名都成功生成了序列数据。两个治疗组各有 3 名患者（100 天组：3/163（1.8%）与 200 天组：3/155（1.9%））检测到单个已知的缬更昔洛韦耐药突变（100 天组：UL97 基因：M460V，C592G 各两次；200 天组：UL97 基因：C603W，M460V 和 UL54 基因：P522S）。总体而言，如果患者在预防治疗期间符合 RAC（5/12（42%）），则更有可能检测到耐药突变，而在预防治疗后（1/58（2%））则较少。所有 6 名已知更昔洛韦耐药突变的患者清除了病毒；3 名患者未治疗即清除了病毒，3 名患者经治疗后清除了病毒。
将缬更昔洛韦预防治疗时间从 100 天延长至 200 天不会显著影响更昔洛韦耐药的发生率。
