Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Hematology, Kansai Electrical Power Hospital, Osaka, Japan.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Hematology, Kyoto-Katsura Hospital, Kyoto, Japan.
J Infect Chemother. 2021 May;27(5):755-758. doi: 10.1016/j.jiac.2020.12.013. Epub 2020 Dec 25.
Varicella zoster virus (VZV) reactivates more frequently in immunocompromised patients than immunocompetent subjects and is a significant cause of morbidity and mortality. Acyclovir is frequently used for treatment against VZV reactivation. However, long-term use of acyclovir can result in the emergence of VZV strain resistant to acyclovir. Here, we report a 67-year-old man with adult T-cell leukemia who suffered from herpes zoster with acyclovir-resistant VZV after long-term prophylaxis. The isolated viruses from his skin lesions were a mixture of acyclovir-resistant and acyclovir-susceptible strains. Sequence analysis showed the presence of thymidine kinase (TK) mutations in the resistant clones. Interestingly, oral administration of famciclovir, a prodrug form of penciclovir, resulted in resolution of his herpes zoster, although most acyclovir-resistant strains of VZV were reported to be resistant to penciclovir. This implied that a certain amount of susceptible VZV with wild-type viral TK gene was present in vivo, and that famciclovir could be phosphorylated intracellularly by the intact viral kinases. As famciclovir is more potent and longer-acting than acyclovir, the susceptible strains might have suppressed the generation and proliferation of the resistant in vivo. Even when VZV is developing resistance to acyclovir, famciclovir might be effective at least in the early resistant phase.
水痘带状疱疹病毒（VZV）在免疫功能低下的患者中比免疫功能正常的患者更容易激活，是发病率和死亡率的重要原因。阿昔洛韦常用于治疗 VZV 再激活。然而，长期使用阿昔洛韦会导致 VZV 株对阿昔洛韦产生耐药性。在这里，我们报告了一例 67 岁男性，患有成人 T 细胞白血病，在长期预防治疗后出现疱疹性带状疱疹，且 VZV 对阿昔洛韦耐药。从他皮肤损伤中分离出的病毒是阿昔洛韦耐药和阿昔洛韦敏感株的混合物。序列分析显示耐药克隆中存在胸苷激酶（TK）突变。有趣的是，口服喷昔洛韦前药泛昔洛韦可使他的带状疱疹消退，尽管据报道大多数阿昔洛韦耐药的 VZV 株对喷昔洛韦耐药。这意味着体内存在一定数量的野生型病毒 TK 基因的敏感 VZV，泛昔洛韦可被完整的病毒激酶在细胞内磷酸化。由于泛昔洛韦比阿昔洛韦更有效且作用时间更长，敏感株可能在体内抑制了耐药株的产生和增殖。即使 VZV 对阿昔洛韦产生耐药性，泛昔洛韦在早期耐药阶段也可能有效。
