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斯洛文尼亚的 HIV-1 传播耐药性及其对预测治疗效果的影响:2011-2016 年更新。

HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update.

机构信息

Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Dr. Fran Mihaljević University Hospital for Infectious Diseases, Zagreb, Croatia.

出版信息

PLoS One. 2018 Apr 26;13(4):e0196670. doi: 10.1371/journal.pone.0196670. eCollection 2018.

DOI:10.1371/journal.pone.0196670
PMID:29698470
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5919638/
Abstract

HIV-positive individuals that have a detected transmitted drug resistance (TDR) at baseline have a higher risk of virological failure with antiretroviral therapy (ART). This study offers an update on the prevalence of TDR in Slovenia, looks for onward transmission of TDR, and reassesses the need for baseline drug resistance testing. Blinded questionnaires and partial pol sequences were obtained from 54.5% (168/308) of all of the patients diagnosed with HIV-1 from 2011 to 2016. Subtype B was detected in 82.7% (139/168) of patients, followed by subtype A (8.3%), subtype C (2.4%), and CRF01_AE (1.8%). Surveillance drug resistance mutations (SDRMs) were found in four individuals (2.4%), all of them men who have sex with men (MSM) and infected with subtype B. K103N was detected in two patients and T68D and T215D in one person each, corresponding to a prevalence of 0%, 1.2%, and 1.2% of TDR to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs), respectively. The impact of mutations on drug susceptibility was found to be most pronounced for NNRTIs. No forward spread of TDR within the country was observed; however, phylogenetic analysis revealed several new introductions of HIV into Slovenia in recent years, possibly due to increased risky behavior by MSM. This was indirectly confirmed by a substantial increase in syphilis cases and HIV-1 non-B subtypes during the study period. A drug-resistant HIV variant with good transmission fitness is thus more likely to be imported into Slovenia in the near future, and so TDR should be closely monitored.

摘要

HIV 阳性个体在基线时检测到传播耐药性(TDR),其接受抗逆转录病毒治疗(ART)后发生病毒学失败的风险更高。本研究更新了斯洛文尼亚 TDR 的流行率,寻找 TDR 的传播,重新评估了基线耐药性检测的必要性。从 2011 年至 2016 年诊断为 HIV-1 的所有患者中,获得了 54.5%(168/308)的盲法问卷和部分 pol 序列。82.7%(139/168)的患者检测到 B 亚型,其次是 A 亚型(8.3%)、C 亚型(2.4%)和 CRF01_AE(1.8%)。在四名患者(2.4%)中发现了监测耐药性突变(SDRMs),他们均为男男性行为者(MSM)且感染 B 亚型。两名患者检测到 K103N,一名患者检测到 T68D 和 T215D,分别对应蛋白酶抑制剂(PIs)、核苷逆转录酶抑制剂(NRTIs)和非核苷逆转录酶抑制剂(NNRTIs)的 TDR 发生率为 0%、1.2%和 1.2%。突变对药物敏感性的影响在 NNRTIs 中最为明显。未观察到 TDR 在国内的传播;然而,系统进化分析显示,近年来 HIV 病毒在斯洛文尼亚的传入有所增加,可能是由于 MSM 的危险行为增加所致。在此期间梅毒病例和 HIV-1 非 B 亚型的大量增加间接证实了这一点。因此,在不久的将来,更有可能将具有良好传播适应性的耐药性 HIV 变异体输入斯洛文尼亚,因此应密切监测 TDR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c5/5919638/bf5cd142e172/pone.0196670.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c5/5919638/a36b388546cb/pone.0196670.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c5/5919638/bf5cd142e172/pone.0196670.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c5/5919638/a36b388546cb/pone.0196670.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c5/5919638/bf5cd142e172/pone.0196670.g002.jpg

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