Correlation between rules-based interpretation and virtual phenotype interpretation of HIV-1 genotypes for predicting drug resistance in HIV-infected individuals
Correlation between rules-based interpretation and virtual phenotype interpretation of HIV-1 genotypes for predicting drug resistance in HIV-infected individuals
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DOI：
10.1016/j.jviromet.2004.06.003
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Soriano, V
中科院分区：
文献类型：
--
作者：
Gallego, O;Martin-Carbonero, L;Soriano, V
耐药性测试为管理艾滋病毒感染患者提供了有用的信息。表型分型可以为基因分型提供补充信息，并且偶尔会更有用，尽管临床医生较少使用。大型配对基因-表型数据库允许从基因型预测表型。然而，这些虚拟表型（vPT）在临床环境中的准确性尚未得到很好的评估。我们分析了105个hiv感染者样本中vPT和解释基因型（GT）之间的一致性。当检测非核苷类逆转录酶抑制剂（NNRTI）和蛋白酶抑制剂（PI）时，可以看到高度的一致性（r = 0.95），而核苷类似物的一致性较低（r = 0.79）。一致性较低的药物为阿巴卡韦（71.1%）、替诺福韦（71.5%）和二腺苷（71.9%）。在20%的样本（21/105）中，vPT没有提供所有批准药物的结果。这些主要是具有大量耐药突变或罕见基因型的样本，这些样本似乎在VircoNET（TM）数据库中代表性不足。总体而言，vPT/GT具有良好的相关性，特别是PI与NNRTI。在VircoNET（TM）数据库中加入额外的序列，主要是那些来自有大量治疗经验的患者和/或来自最近批准的药物失败的患者的序列，可能会提高其性能。(C) 2004 Elsevier B.V.版权所有
Drug resistance testing provides useful information for managing HIV-infected patients. Phenotyping could add complementary information to genotyping and occasionally be more useful, although is less available to clinicians. Large paired geno-pheno databases have allowed the prediction of phenotypes from genotypes. However, the accuracy of these virtual phenotypes (vPT) in a clinical setting has not been well assessed yet. We analyzed the concordance between vPT and interpreted genotype (GT) in 105 samples belonging to treatment-experienced HIV-infected patients. A high concordance was seen when examining both non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) (r = 0.95 either), while it was lower for nucleoside analogs (r = 0.79). The drugs with lower concordance were abacavir (71.1%), tenofovir (71.5%) and didanosine (71.9%). In 20% of specimens (21/105), the vPT did not provide results for all approved drugs. These were mainly samples with a high number of drug resistance mutations or rare genotypes, which seem to be underepresented in the VircoNET(TM) database. Overall, there is good correlation between vPT/GT, especially for PI and NNRTI. The inclusion of additional sequences in the VircoNET(TM) database, mainly those derived from heavily treatment-experienced patients and/or from patients failing the most recently approved drugs might improve its performance. (C) 2004 Elsevier B.V. All rights reserved.