Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice
Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice
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DOI：
10.1093/jac/dkz067
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发表时间：
2019-06-01
影响因子：
5.2
通讯作者：
Palau Concejo, Paula
中科院分区：
文献类型：
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作者：
Alvarez, Marta;Casas, Paz;Palau Concejo, Paula
背景：整合酶链转移抑制剂（INSTIs）目前是一线抗逆转录病毒治疗（ART）的支柱之一。
目的：研究西班牙未接受过抗逆转录病毒治疗的患者中对INSTIs的传播性耐药（TDR）的患病率及其趋势。
方法：在2012 - 2017年期间，对来自CoRIS的1109名患者进行了分析。使用斯坦福算法v8.7评估TDR以及临床相关耐药的传播。为描述个体突变/多态性，使用了最新的国际艾滋病学会（IAS）列表（针对INSTIs）和2009年世界卫生组织（WHO）列表更新（针对一线治疗中与INSTIs联合使用的核苷类逆转录酶抑制剂（NRTIs）骨干药物）。
结果：对INSTI类药物的临床相关耐药率为0.2%：T66I为0.1%，对埃替格韦耐药且对雷特格韦中度耐药；G163K为0.1%，对雷特格韦和埃替格韦中度耐药。未观察到对多替拉韦或比克替拉韦的临床耐药。按照IAS - 美国INSTI突变列表，INSTI的TDR患病率为2.6%，在整个研究期间患病率无变化趋势。NRTI的WHO突变总体患病率为4.3%，而对替诺福韦、阿巴卡韦以及恩曲他滨/拉米夫定的临床相关耐药率分别为1.7%、1.9%和0.7%。
结论：鉴于西班牙对INSTIs和一线NRTIs的临床相关耐药率较低，新诊断的患者对基于INSTI的一线治疗方案出现临床耐药的可能性极小。这些患者可能无法从INSTI和NRTI基线耐药检测中获益。
Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART.Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain.Methods: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used.Results: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/ lamivudine was 1.7%, 1.9% and 0.7%, respectively.Conclusions: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.