喀麦隆抗逆转录病毒初治的 HIV-1 感染者中整合酶抑制剂耐药突变的流行情况。

Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon.

机构信息

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

Paul Ehrlich Institute, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.

出版信息

J Antimicrob Chemother. 2021 Jan 1;76(1):124-129. doi: 10.1093/jac/dkaa383.

DOI:10.1093/jac/dkaa383

PMID:32954411

Abstract

OBJECTIVES

In Cameroon, the integrase (IN) strand transfer inhibitor (INSTI) dolutegravir was recently introduced for the treatment of HIV-1 infection. Since pretreatment HIV-1 drug resistance can jeopardize the success of ART, and considering the high heterogeneity of circulating HIV-1 subtypes in Cameroon, we investigated the prevalence of pretreatment HIV-1 resistance to INSTIs.

METHODS

Fingerprick dried blood spot samples were collected from 339 newly diagnosed HIV-1-infected individuals between 2015 and 2016 in four hospitals in Cameroon. Universal primers were designed to amplify the HIV-1 IN region from amino acid 1 to 276. Amplicons were sequenced with Illumina next-generation sequencing and analysed with the Polymorphism Analysis Sequencing (PASeq) platform, using the Stanford HIV Drug Resistance Database to interpret HIV-1 drug resistance mutations (DRMs).

RESULTS

The amplification/sequencing success rate was 75.2% with 255/339 sequences obtained. Applying a cut-off of 1%, major DRMs to INSTIs were detected in 13 (5.1%) individuals, but only 1 individual harboured an INSTI DRM (E92G) at a nucleotide frequency ≥15%. However, 140/255 (54.9%) individuals harboured polymorphic accessory INSTI DRMs, mainly at high frequencies. In line with that observation, HIV-1 subtype diversity among individuals was high.

CONCLUSIONS

Pretreatment HIV-1 resistance to INSTIs was low in the study sites, which supports the use of INSTIs in Cameroon. Nevertheless, further studies are necessary to assess the impact of polymorphic accessory INSTI DRMs on INSTI-based ART regimens.

摘要

目的

在喀麦隆，整合酶（IN） strand transfer 抑制剂（INSTI）多替拉韦最近被引入用于治疗 HIV-1 感染。由于治疗前 HIV-1 耐药性可能危及 ART 的成功，并且考虑到喀麦隆循环 HIV-1 亚型的高度异质性，我们调查了治疗前 HIV-1 对 INSTIs 的耐药性流行情况。

方法

2015 年至 2016 年期间，在喀麦隆的四家医院采集了 339 名新诊断为 HIV-1 感染的个体的指尖干血斑样本。设计了通用引物以扩增 HIV-1 IN 区从氨基酸 1 到 276。使用 Illumina 下一代测序对扩增子进行测序，并使用 Polymorphism Analysis Sequencing（PASeq）平台进行分析，使用斯坦福 HIV 药物耐药性数据库解释 HIV-1 药物耐药突变（DRMs）。

结果

扩增/测序成功率为 75.2%，获得了 255/339 个序列。应用 1%的截断值，在 13 名（5.1%）个体中检测到主要的 INSTI 耐药突变，但只有 1 名个体在核苷酸频率≥15%时携带 INSTI 耐药突变（E92G）。然而，255 名个体中有 140 名（54.9%）个体携带多态性辅助 INSTI 耐药突变，主要是高频的。与该观察结果一致，个体间 HIV-1 亚型多样性很高。