阿德福韦酯耐药分析

摘要

Adefovir dipivoxil (ADV) is mainly used in naive and lamivudine (LAM)-resistant patients with chronic hepatitis B (CHB). However. ADV resistance, especially multidrug resistance (MDR) to ADV is becoming more frequent and complicated in clinical practice. Generally, in naive CHB patients, the most frequent primary ADV resistances are ri.A.181V/T and rtN236T, and the most frequent MDRs to ADV are rtL180M+M204V+A181V. As for treatment, the resistant mutation of rtA181 V/T is sensitive for en-ticavir (ETV) and tenofovir (TDF), and that of rtN236T for LAM and ETV. MDR to ADV is mainly associated with squential treatment with LAM and ADV or LAM, ADV and ETV. Clinically, according to the resistance types, LAM or ETV add-on ADV combination therapy is firstly recommended for MDR to ADV, and TDF switching therapy is also another optimal option. Furthermore, ADV addon LAM therapy is the first option for LAM-resistant patients instead of ETV switching therapy.%阿德福韦酯(ADV)主要用于慢性乙型肝炎(乙肝)初治和拉米夫定(LAM)耐药后的治疗.ADV耐药特别是多重耐药已成为临床常见且棘手的问题.乙肝初治患者使用ADV最常见的原发性耐药突变类型为rtA181V/T和rtN236T,最常见的多重耐药类型为rtL180M┼M204V┼A181V.RtA181V/T对恩替卡韦(ETV)和替诺福韦酯(TDF),rtN236T对LAM和ETV保持活性;多重耐药主要与LAM→ADV或LAM→ADV→ETV的序贯治疗有关.临床上应根据检出的耐药类型,首选LAM┼ADV、ETV┼ADV联合治疗或改用TDF.LAM耐药后,国内现有药物中应首选加用ADV,而非改用ETV.