Korn Klaus, Reil Heide, Walter Hauke, Schmidt Barbara
Institute of Clinical and Molecular Virology, German National Reference Centre for Retroviruses, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany.
J Clin Microbiol. 2003 Aug;41(8):3559-65. doi: 10.1128/JCM.41.8.3559-3565.2003.
Between January and March 2000, a quality control panel for human immunodeficiency virus (HIV) drug resistance testing was analyzed by 20 laboratories in five countries. The panel consisted of three clinical samples with different drug resistance genotypes and phenotypes and one HIV-negative plasma. Participants were asked to report the methods used for amplification and sequencing, a list of drug resistance-associated mutations that were detected in the protease and reverse transcriptase of each sample, and an interpretation concerning the susceptibility or resistance to 14 antiretroviral drugs. A total of 22 genotypic data sets were generated, which showed an overall good technical quality except for three participants, who failed to report key mutations for drug resistance. Problems were encountered in three respects: (i). resistant minorities of L90M in the protease, which were determined to about 12% by real-time amplification, were only detected by one-fourth of the participants; (ii). newly described resistance mutations were frequently not reported; and (iii). interpretations of drug resistance-associated mutations varied widely, in particular for protease inhibitors. In some cases, different interpretations were caused by differences in the detection of resistant minorities, but even for the same genotypic profile, interpretations varied considerably. Similar discrepancies were revealed if current Web-based interpretation systems were used to predict drug resistance for samples of the proficiency panel. This indicates that a consensus for the interpretation of drug resistance-associated mutations is urgently needed.
2000年1月至3月期间，五个国家的20个实验室对一个人类免疫缺陷病毒（HIV）耐药性检测质量控制样本进行了分析。该样本包括三个具有不同耐药基因型和表型的临床样本以及一份HIV阴性血浆。要求参与者报告用于扩增和测序的方法、在每个样本的蛋白酶和逆转录酶中检测到的耐药相关突变列表，以及关于对14种抗逆转录病毒药物的敏感性或耐药性的解释。总共生成了22个基因型数据集，除了三名未报告耐药关键突变的参与者外，总体技术质量良好。在三个方面遇到了问题：（i）蛋白酶中L90M耐药少数群体，通过实时扩增测定约为12%，只有四分之一的参与者检测到；（ii）新描述的耐药突变经常未被报告；（iii）耐药相关突变的解释差异很大，尤其是对于蛋白酶抑制剂。在某些情况下，不同的解释是由耐药少数群体检测差异导致的，但即使对于相同的基因型谱，解释也有很大差异。如果使用当前基于网络的解释系统来预测能力验证样本的耐药性，也会发现类似的差异。这表明迫切需要就耐药相关突变的解释达成共识。
