Osiowy Carla, Villeneuve Jean-Pierre, Heathcote E Jenny, Giles Elizabeth, Borlang Jamie
Public Health Agency of Canada, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg, Manitoba, Canada.
J Clin Microbiol. 2006 Jun;44(6):1994-7. doi: 10.1128/JCM.02477-05.
The nucleotide analog adefovir dipivoxil (ADV) is an effective antiviral treatment for chronic hepatitis B virus (HBV) infection, with resistance to ADV estimated to occur less frequently than resistance to lamivudine treatment. The detection of ADV resistance mutations is necessary during therapy to monitor and anticipate possible treatment failure. The INNO-LiPA HBV DR v2 (LiPA; Innogenetics, Ghent, Belgium) is a DNA hybridization line probe assay for the detection of HBV polymerase mutations associated with resistance to lamivudine and ADV. Evaluation of this assay to detect ADV resistance mutations was performed by analyzing 38 patients treated with ADV. Serial samples taken at 6-month intervals during treatment were available for most patients. A total of 124 samples were analyzed by both LiPA and sequencing. By LiPA analysis, 12 patients (31.5%) were found to have mutations associated with resistance to ADV (rtA181V/T and/or rtN236T). This contrasted with sequence analysis, which found nine patients (24%) with either or both mutations. Twice as many samples were rtN236T positive by LiPA (18 of 124) compared to sequence analysis (9 of 124). LiPA detected the rtN236T mutation at least 6 months earlier than its detection by sequencing in patients for whom consecutive serum samples were available. Although less sensitive, sequencing has the advantage of providing information on other polymerase mutations not represented on LiPA strips. The INNO-LiPA HBV DR v2 assay is a very sensitive and specific assay for the detection of the rtN236T mutation associated with resistance to ADV.
核苷酸类似物阿德福韦酯（ADV）是治疗慢性乙型肝炎病毒（HBV）感染的一种有效抗病毒药物，据估计，与拉米夫定治疗相比，对ADV产生耐药的情况发生频率较低。在治疗期间检测ADV耐药突变对于监测和预测可能的治疗失败很有必要。INNO-LiPA HBV DR v2（LiPA；比利时根特的Innogenetics公司）是一种DNA杂交线性探针检测法，用于检测与拉米夫定和ADV耐药相关的HBV聚合酶突变。通过分析38例接受ADV治疗的患者，对该检测法检测ADV耐药突变进行了评估。大多数患者在治疗期间每隔6个月采集的系列样本可供使用。通过LiPA和测序对总共124个样本进行了分析。通过LiPA分析，发现12例患者（31.5%）存在与ADV耐药相关的突变（rtA181V/T和/或rtN236T）。这与序列分析结果形成对比，序列分析发现9例患者（24%）存在其中一种或两种突变。与序列分析（124个样本中有9个）相比，LiPA检测到rtN236T阳性的样本数量是其两倍（124个样本中有18个）。对于有连续血清样本的患者，LiPA检测到rtN236T突变比测序至少早6个月。尽管敏感性较低，但测序的优势在于可提供LiPA条带上未显示的其他聚合酶突变的信息。INNO-LiPA HBV DR v2检测法是检测与ADV耐药相关的rtN236T突变的一种非常敏感且特异的检测法。
