Baldanti Fausto, Lilleri Daniele, Campanini Giulia, Comolli Giuditta, Ridolfo Anna Lisa, Rusconi Stefano, Gerna Giuseppe
Servizio di Virologia and Laboratori Sperimentali di Ricerca, IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
J Antimicrob Chemother. 2004 Mar;53(3):536-9. doi: 10.1093/jac/dkh065. Epub 2004 Jan 22.
Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection.
The case of a donor-positive/recipient-negative (D(+)/R(-)) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples.
Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure.
Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D(+)/R(-) transplant recipients.
已发现实体器官移植受者中出现对更昔洛韦耐药的人巨细胞病毒（HCMV）主要与原发性HCMV感染有关。
描述了1例供体阳性/受体阴性（D(+)/R(-)）肺移植患者出现对更昔洛韦和西多福韦耐药的情况。通过每周测定抗原血症、病毒血症和DNA血症来监测HCMV感染。通过细胞因子流式细胞术测定HCMV特异性CD4细胞免疫。直接对血液样本中的HCMV的UL97和UL54基因进行测序，记录耐药HCMV毒株的出现情况。
原发性HCMV感染后，该患者在一年多的时间里反复出现病毒再激活，最终导致选择出一株在UL97基因产物中有突变（A594V）的对更昔洛韦耐药的HCMV毒株。HCMV特异性CD4细胞免疫测定显示免疫反应持续受损。随后的膦甲酸钠治疗仅因肾毒性使病毒从血液中短暂清除。进一步的更昔洛韦治疗在UL97（H520Q）和UL54（P522S）中均诱导产生了新突变，最终出现了对更昔洛韦和西多福韦的双重耐药。该患者最终死于呼吸衰竭。
测定HCMV特异性CD4细胞免疫可能有助于预测D(+)/R(-)移植受者中耐药毒株的出现。
