抗病毒预防疗法。
这种方法主要是讲抗病毒药物的使用,如给所有巨细胞病毒疾病风险的患者缬更昔洛韦或口服或静脉更昔洛韦。 通常情况下,这将包括所有CMV抗体阳性捐赠者,实体器官移植抗体阴性接受者(CMV D +/ R-)者,巨细胞病毒阳性肺移植患者(CMV R +),所有移植患者都接受淋巴细胞减少药物来抑制免疫排斥。 研究表明,预防性抗病毒治疗不仅能减少巨细胞病毒疾病的发病率,还能减少器官移植后的全因死亡率。[65]Humar A, Lebranchu Y, Vincenti F, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010 May;10(5):1228-37.http://www.ncbi.nlm.nih.gov/pubmed/20353469?tool=bestpractice.com[66]Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid organ transplants: a systematic review of randomized clinical trials. Lancet. 2005 Jun 18-24;365(9477):2105-15.http://www.ncbi.nlm.nih.gov/pubmed/15964447?tool=bestpractice.com[67]Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005 Dec 20;143(12):870-80.http://www.ncbi.nlm.nih.gov/pubmed/16365468?tool=bestpractice.com[68]Small LN, Lau J, Snydman DR. Preventing post-organ transplant cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies. Clin Infect Dis. 2006 Oct 1;43(7):869-80.http://www.ncbi.nlm.nih.gov/pubmed/16941368?tool=bestpractice.com[69]Paya C, Humar A, Dominguez E, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004 Apr;4(4):611-20.http://www.ncbi.nlm.nih.gov/pubmed/15023154?tool=bestpractice.com[70]Hodson EM, Ladhani M, Webster AC, et al. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2013;(2):CD003774.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003774.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450543?tool=bestpractice.com 抗病毒预防也用于 CD4T细胞小于50个/μL的巨细胞病毒血清阳性的艾滋病患者。[71]US Public Health Service (USPHS); Infectious Diseases Society of America (IDSA); USPHS/IDSA Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. HIV Clin Trials. 2001 Nov-Dec;2(6):493-554.http://www.ncbi.nlm.nih.gov/pubmed/11742438?tool=bestpractice.com[72]Spector SA, McKinley GF, Lalezari JP, et al. Oral ganciclovir for the prevention of cytomegalovirus disease in persons with AIDS. N Engl J Med. 1996 Jun 6;334(23):1491-7.http://www.nejm.org/doi/full/10.1056/NEJM199606063342302#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/8618603?tool=bestpractice.com[73]Brosgart CL, Louis TA, Hillman DW, et al. A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS. AIDS. 1998 Feb 12;12(3):269-77.http://www.ncbi.nlm.nih.gov/pubmed/9517989?tool=bestpractice.com 尽管预防性抗病毒治疗(例如更昔洛韦)可用于 CD4+ T 细胞<50 个/μL 的 HIV 感染者中,通常情况下,为了升高 CD4+ T 细胞计数,优先选择抗逆转录病毒治疗 (ART)。当在这些患者中考虑增加进一步的预防性治疗时,药物负担和额外的药物副作用是重要的考虑因素。
一般不对造血干细胞移植的患者进行预防性抗病毒治疗,因为更昔洛韦会引起骨髓抑制,使骨髓植入延迟, 当一些患者在骨髓移植之后,一些专家主张进行预防性抗病毒治疗,先行性治疗对于同种异体造血血干细胞移植的患者是一种更常用的方法。 在造血干细胞移植受者中比较预防性治疗与先行性治疗的一项试验显示,在死亡、巨细胞病毒疾病或其他侵入性感染的复合终点上没有显著差异。[74]Boeckh M, Nichols WG, Chemaly RF, et al. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med. 2015 Jan 6;162(1):1-10.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465336/http://www.ncbi.nlm.nih.gov/pubmed/25560711?tool=bestpractice.com 莱特莫韦 (letermovir) 现已被批准用于血清学阳性造血干细胞移植受者的抗病毒预防治疗。[52]Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in cematopoietic-cell transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-44.https://www.nejm.org/doi/10.1056/NEJMoa1706640http://www.ncbi.nlm.nih.gov/pubmed/29211658?tool=bestpractice.com 由于药物成本高,将该药物用于造血干细胞移植受者在高危患者(例如不匹配或不相关的供体、脐血移植或存在移植物抗宿主病)中引起特别关注。
先行性治疗
该方法详细阐述了指抗病毒药物的使用,主要是针对实验室检查发现有无症状的病毒复制的患者,常使用静脉注射更昔洛韦或缬更昔洛韦治疗, 该策略的重要组成部分是检测血液中巨细胞病毒的高敏感性和预测性方法,例如核酸测试 (NAT) 或抗原血症检测。[67]Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005 Dec 20;143(12):870-80.http://www.ncbi.nlm.nih.gov/pubmed/16365468?tool=bestpractice.com[68]Small LN, Lau J, Snydman DR. Preventing post-organ transplant cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies. Clin Infect Dis. 2006 Oct 1;43(7):869-80.http://www.ncbi.nlm.nih.gov/pubmed/16941368?tool=bestpractice.com[75]Strippoli GF, Hodson EM, Jones C, et al. Preemptive treatment of cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation. 2006 Jan 27;81(2):139-45.http://www.ncbi.nlm.nih.gov/pubmed/16436954?tool=bestpractice.com 这些患者抗病毒药物使用的疗程是以 NAT 或抗原血症检测的巨细胞病毒监测结果为指导的。一般来讲,在巨细胞病毒 NAT 或抗原血症检测阴性后 2 周才会停药。先行性治疗相对标准治疗或安慰剂来讲在预防病毒疾病方面更有效,但是没有充足的证据表明先行性治疗对于实体器官移植患者有效。[76]Owers DS, Webster AC, Strippoli GF, et al. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2013;(2):CD005133.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005133.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450558?tool=bestpractice.com