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2015-2016 年在喀麦隆新诊断的个体中,通过基于干血斑(DBS)的下一代测序(NGS)方法检测到的传播 HIV-1 耐药率较低。

Low prevalence of transmitted HIV-1 drug resistance detected by a dried blood spot (DBS)-based next-generation sequencing (NGS) method in newly diagnosed individuals in Cameroon in the years 2015-16.

机构信息

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.

Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

出版信息

J Antimicrob Chemother. 2018 Jul 1;73(7):1917-1929. doi: 10.1093/jac/dky103.

Abstract

OBJECTIVES

To determine the most recent prevalence, transmission patterns and risk factors of transmitted drug-resistance mutations (TDRMs) in Cameroon, we initiated a multicentre study monitoring HIV-1 drug resistance in newly HIV-1-diagnosed individuals using a novel next-generation sequencing (NGS) assay applicable to fingerprick dried blood spot (DBS) samples.

METHODS

Fingerprick DBS samples and questionnaires were collected from 360 newly HIV-1-diagnosed individuals in four hospitals in urban areas in Cameroon in the years 2015-16. We developed an HIV-1 protease and reverse transcriptase drug resistance genotyping assay applicable to DBS samples and HIV-1 genomes of groups M, N and O. The WHO 2009 list of mutations for surveillance of transmitted drug-resistant HIV strains was used to analyse TDRMs.

RESULTS

Applying our 'DBS-NGS-genotypic resistance test', baseline HIV-1 drug resistance data were successfully obtained from 82.8% (298/360) of newly diagnosed individuals. At nucleotide frequencies >15%, TDRMs to NRTIs were observed in 3.0% (9/298), to NNRTIs in 4.0% (12/298) and to PIs in 1.3% (3/240). The NNRTI mutation K103N was most commonly detected (2.7%). Expanding the analysis to low-abundance TDRMs, i.e. 3%-15%, 12 additional individuals (4.0%) harbouring TDRMs were identified. Having unprotected sex with a known HIV-1-positive person was significantly associated with the transmission of DRMs (adjusted OR 9.6; 95% CI 1.79-51.3).

CONCLUSIONS

The prevalence of transmitted HIV-1 drug resistance is currently low in the study sites in Cameroon. Evidence of some risky sexual behaviours depicts a public health problem with possible implications for the prevention of new HIV-1 infections.

摘要

目的

为了确定喀麦隆最近的传播耐药突变(TDRMs)的流行率、传播模式和危险因素,我们启动了一项多中心研究,使用适用于指尖干血斑(DBS)样本的新型下一代测序(NGS)检测方法,监测新诊断的 HIV-1 感染者中的 HIV-1 耐药性。

方法

2015-2016 年,我们从喀麦隆四个城市地区的四家医院中采集了 360 名新诊断的 HIV-1 感染者的指尖 DBS 样本和调查问卷。我们开发了一种适用于 DBS 样本和 HIV-1 M、N 和 O 组病毒基因组的 HIV-1 蛋白酶和逆转录酶药物耐药基因分型检测方法。我们使用世卫组织 2009 年耐药性监测清单来分析 TDRMs。

结果

应用我们的“DBS-NGS-基因型耐药检测”,成功从 82.8%(298/360)的新诊断个体中获得了基线 HIV-1 药物耐药数据。在核苷酸频率>15%时,NRTIs 的 TDRMs 发生率为 3.0%(9/298),NNRTIs 为 4.0%(12/298),PIs 为 1.3%(3/240)。最常见的 NNRTI 突变是 K103N(2.7%)。将分析扩展到低丰度的 TDRMs,即 3%-15%,又发现了 12 名(4.0%)携带 TDRMs 的个体。与已知 HIV-1 阳性者发生无保护性行为与 DRMs 的传播显著相关(调整后的 OR 9.6;95%CI 1.79-51.3)。

结论

目前,喀麦隆研究地点的传播性 HIV-1 耐药率较低。一些危险性行为的证据表明存在公共卫生问题,可能对预防新的 HIV-1 感染产生影响。

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