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2017-2019 年在台湾北部一家三级医院接受联合抗逆转录病毒治疗的低病毒血症 HIV 感染者中耐药突变的流行情况:一项观察性研究。

Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: an observational study in a tertiary hospital in Northern Taiwan, 2017-19.

机构信息

Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.

出版信息

J Antimicrob Chemother. 2021 Feb 11;76(3):722-728. doi: 10.1093/jac/dkaa510.

DOI:10.1093/jac/dkaa510
PMID:33331635
Abstract

BACKGROUND

Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics.

OBJECTIVES

To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV.

METHODS

A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV.

RESULTS

Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV.

CONCLUSIONS

HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.

摘要

背景

有效的抗逆转录病毒治疗(ART)对于抗击 HIV 大流行至关重要。临床上,通过监测血浆病毒载量以实现病毒学抑制是实现最佳 ART 的指导。低于病毒学失败定义水平的低水平病毒血症(LLV)是 ART 失败的危险因素。然而,目前尚无关于 LLV 的治疗共识,主要是因为 HIV-RNA 基因分型的局限性以及由此导致对 LLV 特征的认识不足。

目的

更好地分析经历 LLV 的病例中的耐药突变(DRMs)和相关因素。

方法

本前瞻性观察性研究于 2017 年至 2019 年进行。使用 HIV-DNA 替代 HIV-RNA 进行 HIV 基因分型,并结合深度测序,用于治疗初治和治疗失败以及 LLV 的病例。

结果

在研究中,81 例治疗初治、18 例治疗失败和 16 例 LLV 病例接受了 HIV 基因分型。三分之二(12/16)的 LLV 病例存在 DRMs。与治疗初治组相比,LLV 病例对 NNRTIs 的耐药率更高(69%比 20%,P<0.001),而对 NRTIs 的耐药率更低(25%比 61%,P<0.001)。大约一半的 LLV 病例存在 ART 依从性不佳/ART 中断的问题,并且在 LLV 时,68.8%(11/16)的病例对其 ART 没有显示出耐药性。

结论

LLV 病例的 HIV DRM 谱与治疗初治和治疗失败病例明显不同。对于经历 LLV 发作的病例,可能需要加强 ART 依从性并早期探索潜在的 ART 耐药性。

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