INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France
BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada University of British Columbia, Vancouver, BC, Canada.
J Antimicrob Chemother. 2015 Jul;70(7):2090-6. doi: 10.1093/jac/dkv048. Epub 2015 Mar 8.
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.
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%).
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).
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.
评估基线时少数耐药变异体（MRVs）的流行率及其对病毒学应答的影响。ANRS 139 TRIO 试验评估了拉替拉韦、依曲韦林和达芦那韦联合优化背景治疗在 87%的病例中的效果。这些患者经验丰富，携带多种耐药病毒，但对这三种药物均无耐药性，病毒学抑制水平较高。
在试验基线时对逆转录酶、蛋白酶和整合酶区域进行超深度测序，并根据 ANRS 算法对序列进行解释。使用 MiSeq 和 454 技术（检测下限为 1%）评估少数变异体。
基线时，至少有一种 NRTI、一种 NNRTI、一种 PI、一种主要 PI 或一种整合酶抑制剂耐药相关突变的少数变异体分别存在于 46%、45%、68%、24%和 13%的患者中。考虑到少数变异体，基线时依曲韦林、达芦那韦和拉替拉韦耐药的发生率分别为 29%、40%和 9%。在病毒学失败和病毒学成功的患者中，MRVs 的流行率没有差异，除了基线时存在依曲韦林 MRVs 的患者存在趋势（50%比 26%，P=0.09）。
我们在携带多种耐药病毒的高度预处理患者中发现了高水平的基线时的 MRVs。然而，这些 MRVs 与病毒学失败的风险增加无关，除了依曲韦林 MRVs 存在趋势。
