Jorgenson Margaret R, Descourouez Jillian L, Leverson Glen E, McCreary Erin K, Lucey Michael R, Smith Jeannina A, Redfield Robert R
1 University of Wisconsin Hospital and Clinics, Madison, WI, USA.
2 University of Wisconsin-Madison School of Medicine and Public Health, Department of Surgery, Madison, WI, USA.
Ann Pharmacother. 2018 Jan;52(1):5-10. doi: 10.1177/1060028017728296. Epub 2017 Aug 26.
Following abdominal solid organ transplant (aSOT), valganciclovir (VGC) is recommended for cytomegalovirus (CMV) prophylaxis. This agent is associated with efficacy concerns, toxicity, and emergence of ganciclovir resistance.
To evaluate the incidence of high-dose acyclovir (HD-A) prophylaxis failure in seropositive aSOT recipients (R+).
This was a retrospective, single-center study of R+ transplanted without lymphocyte-depleting induction between January 1, 2000, and June 30, 2013, discharged with 3 months of HD-A prophylaxis (800 mg 4 times daily). The primary outcome was incidence of prophylaxis failure. Secondary outcomes were incidence of biopsy-proven tissue-invasive disease and prophylaxis failure for each allograft subgroup.
A total of 1525 patients met inclusion criteria: 944 renal (RTX), 108 simultaneous pancreas-kidneys (SPK), 462 liver (LTX), and 11 pancreas (PTX) transplant recipients. The composite rate of HD-A prophylaxis failure was 7%; incidence of tissue-invasive disease was 0.4%. Failure rates were 4.5%, 6.1%, 11%, and 20% in the RTX, SPK, LTX, and PTX populations, respectively; tissue-invasive disease rates were 0.2%, 0%, 0.7%, and 10%. Failure occurred more frequently in the LTX and PTX populations ( P < 0.0001, HR = 2.6; P = 0.04 HR = 4.4). Incidence of tissue-invasive disease was minimal and not different in the RTX, LTX and SPK populations ( P = 0.34). When evaluating recipients of seronegative allografts (D-), the composite failure rate was 3.4% with no significant difference between allograft subgroups ( P = 0.45).
HD-A may be a reasonable prophylaxis alternative for D-/R+ recipients, in the absence of lymphocyte-depleting induction, if low incidence viremia is tolerable. Future studies are needed to determine the long-term impact of CMV viremia in the setting of this prophylaxis approach.
在腹部实体器官移植（aSOT）后，推荐使用缬更昔洛韦（VGC）进行巨细胞病毒（CMV）预防。该药物存在疗效问题、毒性以及更昔洛韦耐药性出现等情况。
评估血清学阳性的aSOT受者（R+）中高剂量阿昔洛韦（HD - A）预防失败的发生率。
这是一项回顾性单中心研究，研究对象为2000年1月1日至2013年6月30日期间接受非淋巴细胞清除诱导的R+移植受者，出院时接受为期3个月的HD - A预防（每日4次，每次800毫克）。主要结局是预防失败的发生率。次要结局是经活检证实的组织侵袭性疾病的发生率以及每个同种异体移植亚组的预防失败情况。
共有1525例患者符合纳入标准：944例肾移植（RTX）受者、108例胰肾联合移植（SPK）受者、462例肝移植（LTX）受者和11例胰腺移植（PTX）受者。HD - A预防失败的综合发生率为7%；组织侵袭性疾病的发生率为0.4%。RTX、SPK、LTX和PTX人群的失败率分别为4.5%、6.1%、11%和20%；组织侵袭性疾病率分别为0.2%、0%、0.7%和10%。失败在LTX和PTX人群中更频繁发生（P < 0.0001，HR = 2.6；P = 0.04，HR = 4.4）。RTX、LTX和SPK人群中组织侵袭性疾病的发生率极低且无差异（P = 0.34）。在评估血清学阴性的同种异体移植受者（D -）时，综合失败率为3.4%，同种异体移植亚组之间无显著差异（P = 0.45）。
如果低发生率的病毒血症可以耐受，对于未进行淋巴细胞清除诱导的D - /R+受者，HD - A可能是一种合理的预防替代方案。需要进一步研究来确定这种预防方法背景下CMV病毒血症的长期影响。
