De Francesco Maria Antonia, Izzo Ilaria, Properzi Martina, Gargiulo Franco, Caccuri Francesca, Quiros-Roldan Eugenia, Castelli Francesco, Caruso Arnaldo, Focà Emanuele
1 Department of Molecular and Translational Medicine, Institute of Microbiology, University of Brescia , Brescia, Italy .
2 University Department of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital , Brescia, Italy .
AIDS Res Hum Retroviruses. 2018 Jul;34(7):570-574. doi: 10.1089/AID.2018.0006. Epub 2018 May 9.
Integrase strand transfer inhibitor (InSTI) resistance rates are low. However, genotypic resistance test (GRT) is not routinely performed in many centers. The aim of this study is to evaluate the prevalence of InSTI-related mutations in our large cohort. We examined all integrase GRTs performed as part of routine clinical practice at Spedali Civili General Hospital, University of Brescia from 2011 to 2016. Analysis was performed through the Stanford HIV Drug Resistance Database. A total of 341 patients were included. Genotypic resistance assays were performed in naive (48), ART-experienced but InSTI-naive (114), and both ART-experienced/InSTI-experienced (179) patients. No major resistance-associated mutations (RAMs) were detected in patients never exposed to InSTIs. Of 179 samples from patients exposed to InSTIs (mostly to raltegravir [RAL]), the overall prevalence of major RAMs was 11.7%. Among them, 10 harbored N155H, 4 Q148H, 2 Q148R, 2 Y143C/S, and 2 T66A/I/T, respectively. A novel mutation at a recognized resistance site (E92K) was identified in one RAL-experienced patient. The overall prevalence of InSTI mutations in our cohort was low, particularly in naive patients indicating no transmitted RAMs, although in InSTIs-experienced patients the rate of RAMs was high (11.7%). We support an implementation of surveillance of InSTI resistance.
整合酶链转移抑制剂(InSTI)的耐药率较低。然而,许多中心并未常规开展基因型耐药检测(GRT)。本研究的目的是评估我们这个大型队列中InSTI相关突变的流行情况。我们检查了2011年至2016年在布雷西亚大学公民综合医院作为常规临床实践一部分所进行的所有整合酶GRT。通过斯坦福HIV耐药数据库进行分析。共纳入341例患者。对初治患者(48例)、有抗逆转录病毒治疗(ART)经验但未使用过InSTI的患者(114例)以及既有ART经验又有InSTI使用经验的患者(179例)进行了基因型耐药检测。在从未接触过InSTI的患者中未检测到主要耐药相关突变(RAM)。在179例接触过InSTI(主要是拉替拉韦[RAL])的患者样本中,主要RAM的总体流行率为11.7%。其中,分别有10例携带N155H、4例携带Q148H、2例携带Q148R、2例携带Y143C/S以及2例携带T66A/I/T。在1例有RAL使用经验的患者中发现了一个公认耐药位点的新突变(E92K)。我们队列中InSTI突变的总体流行率较低,尤其是在初治患者中,表明没有传播性RAM,尽管在有InSTI使用经验的患者中RAM发生率较高(11.7%)。我们支持实施InSTI耐药监测。