拉米夫定和阿德福韦酯联合用药对慢性乙型肝炎感染的持续病毒学和生化反应,尽管突变使两种药物产生耐药性。

Sylvie Larrat, Marie-Noëlle Hilleret, Raphaele Germi, Julien Lupo, Sandrine Nicod, Jean-Pierre Zarski, Jean-Marie Seigneurin, Patrice Morand
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引用次数: 6

摘要

背景:用于慢性乙型肝炎治疗的核苷酸类似物的序贯单药治疗可导致对每种抗病毒药物的抗性突变的选择。病例介绍:慢性乙型肝炎患者先后接受拉米夫定单药治疗、拉米夫定-阿德福韦双药治疗、阿德福韦单药治疗和再次接受阿德福韦-拉米夫定双药治疗。拉米夫定相关突变(rtL180M和rtM204V/I)和阿德福韦相关突变(rtN236T和rtA181V)在两种单药治疗方案中出现。尽管在第二次双重治疗开始时存在rtM204V/I、rtA181V和rtN236T突变,但到目前为止,23个月后观察到持续的生化和病毒学反应。结论:该病例表明,rtM204V/I、rtA181V和rtN236T耐药突变可以在同一患者中共存,但在没有其他治疗选择的情况下,并不妨碍拉米夫定和阿德福韦联合治疗的循环使用。
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Sustained virological and biochemical responses to lamivudine and adefovir dipivoxil combination in a chronic hepatitis B infection despite mutations conferring resistance to both drugs.

Background: Sequential monotherapies of nucleotide analogs used in chronic hepatitis B treatment can lead to the selection of a resistance mutation to each antiviral drug.

Case presentation: A patient with chronic hepatitis B was successively treated with lamivudine monotherapy, lamivudine-adefovir dual therapy, adefovir monotherapy and again with an adefovir-lamivudine dual therapy. Lamivudine-associated mutations (rtL180M and rtM204V/I) followed by adefovir-associated mutations (rtN236T and rtA181V) emerged during the two monotherapy regimens. Despite the presence of rtM204V/I, rtA181V, and rtN236T mutations at the beginning of the second dual therapy, sustained biochemical and virological responses have been observed thus far after 23 months.

Conclusion: This case illustrates that rtM204V/I, rtA181V, and rtN236T resistance mutations can coexist in a patient but do not preclude the recycling of lamivudine and adefovir in combination therapy, when no other therapeutic choices are available.

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