Morfin F, Frobert E, Thouvenot D
Laboratoire de virologie des Hospices civils de Lyon, Domaine Rockefeller, 8 avenue Rockefeller, 69373 Lyon cedex 08.
Ann Biol Clin (Paris). 2003 Jan-Feb;61(1):33-40.
Herpes simplex virus (HSV) and varicella zoster virus (VZV) are susceptible to acyclovir which inhibits viral replication through two viral enzymes, thymidine kinase (TK) and DNA polymerase. Resistance may occur, it is a rare phenomenon among immunocompetent patients but resistance is more frequent and may be associated with serious complications among immunocompromised patients. Virological survey of these at risk patients is needed to detect resistant virus as soon as possible through phenotypic tests performed on virus isolated on cell cultures. Resistant virus may also be genetically characterised by detection of mutations within TK and DNA polymerase genes. Pharmacological parameters also have to be taken into consideration and a determination of acyclovir blood concentration should be performed in case of unexplained therapeutic failure. Improvement of immune system, when possible, may resolve these infections. Alternative treatments using drugs such as foscarnet or cidofovir which have a different mechanism of action compared to acyclovir, are recommended but these molecules are often more toxic than acyclovir.
单纯疱疹病毒（HSV）和水痘带状疱疹病毒（VZV）对阿昔洛韦敏感，阿昔洛韦通过两种病毒酶，即胸苷激酶（TK）和DNA聚合酶来抑制病毒复制。可能会出现耐药情况，在免疫功能正常的患者中这是一种罕见现象，但在免疫功能低下的患者中耐药更为常见，且可能与严重并发症相关。需要对这些高危患者进行病毒学检测，以便通过对细胞培养物中分离出的病毒进行表型试验尽快检测出耐药病毒。耐药病毒也可通过检测TK和DNA聚合酶基因内的突变进行基因特征分析。还必须考虑药理学参数，在出现无法解释的治疗失败时应测定阿昔洛韦血药浓度。如有可能，改善免疫系统可能会解决这些感染问题。建议使用膦甲酸钠或西多福韦等药物进行替代治疗，这些药物与阿昔洛韦的作用机制不同，但这些分子通常比阿昔洛韦毒性更大。
