在法国和意大利的临床环境中，对使用含有多替拉韦方案失败的个体进行整合酶耐药性评估。

Evaluation of integrase resistance in individuals who failed a regimen containing dolutegravir in French and Italian clinical settings.

机构信息

Saint Camillus International University of Health Sciences, Rome, Italy.

University of Rome 'Tor Vergata', Rome, Italy.

出版信息

J Antimicrob Chemother. 2023 Jun 1;78(6):1415-1422. doi: 10.1093/jac/dkad101.

DOI:10.1093/jac/dkad101

PMID:37258034

Abstract

BACKGROUND

This work aims to evaluate integrase resistance and its predictors in HIV-1 infected combined antiretroviral therapy (cART) experienced individuals failing a dolutegravir-based regimen.

METHODS

Major resistance mutations (MRM) and genotypic susceptibility score (GSS) of dolutegravir companion drugs were evaluated on plasma genotypic resistance test (GRT) performed at dolutegravir failure. Logistic regression was used to evaluate factors associated to the risk of integrase strand-transfer inhibitors (INSTI)-resistance at dolutegravir failure.

RESULTS

We retrospectively analysed 467 individuals. At failure GRT, individuals had been under dolutegravir for a median (IQR) time of 11 (5-20) months; around half of them had never been exposed to INSTI (52%) and 10.7% were at first-line regimen. Fifty-eight (12.4%) individuals showed ≥1 INSTI MRM. Among them, people INSTI-exposed showed significantly higher prevalence of INSTI resistance compared to those who were INSTI naïve [46 (21.2%) versus 9 (3.9%), P < 0.001].N155H was the most prevalent MRM (5.4%), followed by G140S (4.5%) and Q148H (4.3%). These MRM were more probably present in INSTI-experienced individuals compared to those INSTI naïve. Despite failure, 89.5% of individuals harboured viral strains fully susceptible to dolutegravir and bictegravir and 85.0% to all INSTI. No INSTI exposure before receiving dolutegravir [OR: 0.35 (0.16-0.78), P < 0.010] and a GSS for companion drugs ≥2 (OR: 0.09 [0.04-0.23], P < 0.001) were negatively associated with INSTI resistance at failure.

CONCLUSIONS

In a large set of individuals failing dolutegravir in real-life, INSTI resistance was low and mainly related to previous first-generation INSTI exposure. Surveillance of integrase resistance remains crucial to preserve efficacy of INSTI class in the future.

摘要

背景

本研究旨在评估在接受多替拉韦为基础的治疗方案失败的 HIV-1 感染的接受过联合抗逆转录病毒治疗（cART）的个体中整合酶耐药及其预测因素。

方法

在多替拉韦失败时进行的血浆基因型耐药检测（GRT）上评估了多替拉韦伴随药物的主要耐药突变（MRM）和基因型耐药评分（GSS）。采用 logistic 回归评估与多替拉韦失败时整合酶转位抑制剂（INSTI）耐药风险相关的因素。

结果

我们回顾性分析了 467 名个体。在 GRT 失败时，个体接受多替拉韦治疗的中位（IQR）时间为 11（5-20）个月；其中约一半从未接触过 INSTI（52%），10.7%为一线方案。58（12.4%）名个体出现了≥1 个 INSTI-MRM。其中，曾接触过 INSTI 的个体与未接触过 INSTI 的个体相比，INSTI 耐药的患病率明显更高[46（21.2%）比 9（3.9%），P＜0.001]。N155H 是最常见的 MRM（5.4%），其次是 G140S（4.5%）和 Q148H（4.3%）。与未接触过 INSTI 的个体相比，这些 MRM 在接触过 INSTI 的个体中更常见。尽管失败，但 89.5%的个体携带对多替拉韦和比克替拉韦完全敏感的病毒株，85.0%对所有 INSTI 敏感。在接受多替拉韦之前没有 INSTI 暴露[OR：0.35（0.16-0.78），P＜0.010]和伴随药物的 GSS≥2[OR：0.09（0.04-0.23），P＜0.001]与失败时的 INSTI 耐药呈负相关。