Clinically relevant interpretation of genotype for resistance to abacavir
Clinically relevant interpretation of genotype for resistance to abacavir
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DOI：
10.1097/00002030-200308150-00008
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发表时间：
2003-08-15
期刊：
影响因子：
3.8
通讯作者：
Costagliola, D
中科院分区：
文献类型：
--
作者：
Brun-Vézinet, F;Descamps, D;Costagliola, D
目的：开发一种逐步方法来开发和验证抗逆转录病毒药物耐药性的临床相关基因型评分，并将该方法应用于阿巴卡韦基因型耐药性。方法：本研究纳入了在 Narval 试验期间接受阿巴卡韦治疗的所有患者。通过单变量分析研究了每种核苷类似物耐药突变对阿巴卡韦病毒学反应的影响。 P 值 < 0.20 的突变和阿巴卡韦选择的突变被保留。根据突变的数量定义了三个耐药水平。考虑混杂变量的多变量分析评估了基因型评分是否是反应的独立预测因子。使用引导重采样方法分析评分的稳健性。 结果：在 175 名暴露于阿巴卡韦的患者中，观察到逆转录酶基因密码子 41、67、210、215、74 和 184 处的一组 6 个突变导致病毒载量下降与突变数量之间的最强关联。在少于 4 个突变（无耐药证据）的患者中，病毒载量中位数下降为 -1.64 log(10) 拷贝/ml，而在有 4 个（可能耐药）和 5 个或 6 个（耐药）突变的患者中，病毒载量中值下降分别为 -0.69 log(10) 和 -0.19 log(10)。在多变量分析中，该分数是反应的独立预测因子。引导分析显示了评分的稳健性。结论：我们开发了一种新策略来分析基线基因型谱与病毒学反应之间的相关性。 (C) 2003 年利平科特威廉姆斯和威尔金斯。
Objective: To develop a stepwise methodology for the development and validation of clinically relevant genotypic score for resistance to antiretroviral drugs and to apply this approach to the genotypic resistance to abacavir.Methods: All patients having received abacavir during the Narval trial were included in this study. The impact of each nucleoside analogue resistance mutation on the virologic response to abacavir was studied in a univariate analysis. Mutations with a P value < 0.20 and those selected by abacavir were retained. According to the number of mutations three levels of resistance were defined. A multivariate analysis accounting for confonding variables assessed whether the genotypic score was an independent predictor of the response. The robustness of the score was analysed using the bootstrap resampling method.Results: In the 175 patients exposed to abacavir, the strongest association between the decrease in viral load and the number of mutations was observed with a set of six mutations at codons 41, 67, 210, 215, 74 and 184 of the reverse transcriptase gene. In patients with fewer than four mutations (no evidence of resistance) the median decrease in viral load was -1.64 log(10) copies/ml while it was -0.69 log(10) and -0.19 log(10) in those with four (possible resistance) and five or six (resistance) mutations respectively. In the multivariate analysis this score was an independent predictor of the response. The bootstrap analysis showed the robustness of the score.Conclusions: We developed a new strategy for the analysis of correlation between genotype profile at baseline and virologic response. (C) 2003 Lippincott Williams & Wilkins.