Highly frequent HIV-1 minority resistant variants at baseline of the ANRS 139 TRIO trial had a limited impact on virological response
Highly frequent HIV-1 minority resistant variants at baseline of the ANRS 139 TRIO trial had a limited impact on virological response
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DOI：
10.1093/jac/dkv048
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发表时间：
2015-07-01
影响因子：
5.2
通讯作者：
Descamps, Diane
中科院分区：
文献类型：
--
作者：
Charpentier, Charlotte;Lee, Guinevere Q.;Descamps, Diane
目的：评估基线时少数耐药变异（MRV）的患病率及其对病毒学应答的影响。ANRS 139 TRIO试验在87%的病例中评估了雷特格韦、依曲韦林和地瑞那韦的联合治疗，以及优化的背景治疗。患者经验丰富，窝藏多重耐药病毒，但幼稚的三种药物，并表现出高水平的病毒学suppress.Methods：超深测序的逆转录酶，蛋白酶和整合酶区域进行了试验基线，并根据ANRS算法序列进行解释。使用MiSeq和454技术评估MRV（检测限1%）。结果：在基线时，至少有一个NRTI，一个NNRTI，一个PI，一个主要PI或整合酶抑制剂耐药相关突变的少数变异分别存在于46%，45%，68%，24%和13%的患者中。当考虑到少数变异时，基线时对依曲韦林、达芦那韦和雷特格韦的耐药率分别为29%、40%和9%。没有观察到病毒学失败的患者和病毒学成功的患者之间的MRV的患病率有差异，除了表现出基线依曲韦林MRV的患者的趋势（50%对26%，P = 0.09）。结论：我们已经显示了高水平的MRV在基线高度预治疗的患者携带多重耐药病毒。然而，除了依曲韦林MRV的趋势外，这些MRV与病毒学失败的风险增加无关。
Objectives: To assess the prevalence of minority resistant variants (MRVs) at baseline and their impact on the virological response. The ANRS 139 TRIO trial evaluated the combination of raltegravir, etravirine and darunavir, plus an optimized background therapy, in 87% of cases. Patients were highly experienced and harboured multiresistant viruses, but were naive to the three drugs, and showed a high level of virological suppression.Methods: Ultra-deep sequencing of reverse transcriptase, protease and integrase regions was performed at the trial baseline, and sequences were interpreted according to the ANRS algorithm. MRVs were assessed using MiSeq and 454 technologies (limit of detection 1%).Results: At baseline, minority variants with at least one NRTI, one NNRTI, one PI, one major PI or an integrase inhibitor resistance-associated mutation were present in 46%, 45%, 68%, 24% and 13% of patients, respectively. When minority variants are taken into account, the prevalence of resistance to etravirine, darunavir and raltegravir at baseline was 29%, 40% and 9%, respectively. No difference was observed in the prevalence of MRVs between patients with virological failure and those with virological success, except a trend for patients exhibiting baseline etravirine MRVs (50% versus 26%, P = 0.09).Conclusions: We have shown a high level of MRVs at baseline in highly pre-treated patients harbouring multiresistant viruses. However, these MRVs were not associated with an increased risk of virological failure, except for a trend for etravirine MRVs.