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.

译文

目的:在喀麦隆,最近引入了整合酶(IN)链转移抑制剂(INSTI)多洛格韦用于治疗HIV-1感染。由于预处理HIV-1的耐药性可能会危害ART的成功,并且考虑到喀麦隆循环中HIV-1亚型的高度异质性,我们研究了预处理HIV-1对INSTIs耐药的普遍性。
方法:2015年至2016年之间,在喀麦隆的四家医院中,从339名新诊断的HIV-1感染者中采集了指尖干血斑样本。设计通用引物以扩增HIV-1 IN区(氨基酸1至276)。使用Illumina下一代测序技术对扩增子进行测序,并使用多态性分析测序(PASeq)平台进行分析,并使用斯坦福大学HIV耐药数据库来解释HIV -1耐药性突变(DRM)。
结果:扩增得到255/339个序列,成功率为75.2%。临界值设为1%时,在13名(5.1%)个体中检测到了主要的INRMs DRM,但只有1名个体的核苷酸频率≥15%带有INSTI DRM(E92G)。但是,有140/255(54.9%)个人携带多态附件INSTI DRM,主要是在高频下。与该观察结果一致,个体间HIV-1亚型的多样性很高。
结论:在研究地点,HIV-1对INSTIs的抗药性较低,这支持在喀麦隆使用INSTIs。尽管如此,仍需要进一步的研究来评估多态性辅助INSTI DRM对基于INSTI的ART方案的影响。

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