Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients
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DOI：
10.1093/jac/dku535
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发表时间：
2015-05-01
影响因子：
5.2
通讯作者：
Marcelin, Anne-Genevieve
中科院分区：
文献类型：
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作者：
Fourati, Slim;Charpentier, Charlotte;Marcelin, Anne-Genevieve
目的：本研究的目的是确定在基于雷特格韦的抗逆转录病毒治疗（ART）中出现病毒学失败的患者对整合酶链转移抑制剂（INSTIs）的耐药率和耐药模式，以及对INSTIs（雷特格韦、埃替格韦和多替拉韦）敏感性的影响。
患者和方法：在一项多中心研究中，从502名接受含雷特格韦方案治疗失败的有治疗经验的患者中收集数据。在失败时对每位患者的逆转录酶、蛋白酶和整合酶进行测序。所研究的INSTI耐药相关突变是上次法国国家艾滋病研究署（ANRS）基因型算法（v23版）中包含的那些突变。
结果：在502名患者中，失败时，HIV - 1 RNA（病毒载量）的中位基线为2.9 log(10)拷贝/毫升。患者先前平均接触过5种核苷类逆转录酶抑制剂（NRTIs）、1种非核苷类逆转录酶抑制剂（NNRTI）和3种蛋白酶抑制剂（PIs）。71%的患者携带HIV - 1 B亚型，最常见的非B亚型是CRF02_AG（13.3%）。观察到的最常见突变是N155H/S（19.1%）、Q148G/H/K/R（15.4%）和Y143C/G/H/R/S（6.7%）。在失败时，61.0%的病例中病毒被认为对所有INSTIs完全敏感，而38.6%被认为对雷特格韦耐药，34.9%对埃替格韦耐药，13.9%对多替拉韦耐药。在对雷特格韦耐药的情况下，11%的病例中病毒被认为对埃替格韦敏感，64%的病例中对多替拉韦敏感。失败时HIV - 1病毒载量高（P<...此处原文似乎不完整）
Objectives: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).Patients and methods: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).Results: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log(10) copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P