International perspectives on antiretroviral resistance. Phenotypic and genotypic resistance assays: methodology, reliability, and interpretations.

International perspectives on antiretroviral resistance. Phenotypic and genotypic resistance assays: methodology, reliability, and interpretations.
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关于抗逆转录病毒耐药性的国际观点。

DOI:
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发表时间:
2001
期刊:
Journal of Acquired Immune Deficiency Syndromes
影响因子:
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通讯作者:
R. Haubrich
R. Haubrich
中科院分区:
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文献类型:
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作者:
L. Demeter;R. Haubrich

文献摘要

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表型和基因型耐药性测定(测量艾滋病毒对药物治疗敏感性的方法)正被临床医生广泛使用,用于帮助制定长期抗逆转录病毒治疗计划。表型测试评估患者的病毒分离株对培养中的单个抗逆转录病毒药物的实际反应,基因型测试对病毒 DNA 进行测序,根据评估者对抗逆转录病毒药物耐药性的既定 HIV-1 基因突变模式的了解,提供推断的耐药性测量。这些测试如果按预期使用,可以提供有助于规划成功的抗逆转录病毒治疗方案的信息。两种类型的检测均已被证明可以提供可靠且可重复的耐药性测量,但有一定的注意事项:准确性取决于翻译人员和实验室的经验;现有测试的结果不可互换,临床相关的耐药阈值尚未完全确定。由于药代动力学和交叉耐药性问题,将单一药物数据外推至联合治疗方案很难完成,必须与治疗和病毒载量历史合并,以最好地确定有效的后续治疗方案。本文描述了迄今为止确定当今使用的表型和基因型耐药测定的功效、准确性、重现性和局限性的经验。
Phenotypic and genotypic resistance assays-methods to measure the susceptibility of HIV to drug therapy-are becoming widely available to clinicians for use in aiding long-term antiretroviral treatment planning. Phenotypic tests assess the actual response of a patient's viral isolate to individual antiretroviral drugs in culture, and genotypic tests sequence viral DNA, providing an inferred measure of resistance based on the evaluator's knowledge of established HIV-1 genetic mutational patterns for resistance to antiretroviral drugs. These tests, when used as intended, can provide information useful in planning successful antiretroviral regimens. Both types of assays have been shown to provide reliable and reproducible measures of resistance, with certain caveats: accuracy depends on the experience of the interpreter and laboratory; results from the available tests are not interchangeable, and clinically relevant thresholds of resistance have not been fully defined. Because of pharmacokinetic and cross-resistance issues, the extrapolation of single-drug data to combination regimens is difficult to accomplish and must be pooled with treatment and viral load history to best identify effective subsequent treatment regimens. This article describes the experience to date establishing the efficacy, accuracy, reproducibility, and limitations of the phenotypic and genotypic resistance assays used today.