Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon
Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon
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DOI：
10.1093/jac/dkaa383
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发表时间：
2021-01-01
影响因子：
5.2
通讯作者：
Metzner, Karin J.
中科院分区：
文献类型：
--
作者：
Wenk, Benjamin M.;Mbunkah, Herbert A.;Metzner, Karin J.
目的：在喀麦隆，整合酶链转移抑制剂dolutegravir最近被用于治疗HIV-1感染。由于治疗前HIV-1耐药性可能危及ART的成功，并考虑到喀麦隆流行的HIV-1亚型的高度异质性，我们调查了治疗前HIV-1对INSTIs.Methods耐药的患病率：从2015年至2016年期间喀麦隆4家医院的339名新诊断的HIV-1感染者中收集手指刺干血斑样本。设计通用引物以扩增从氨基酸1至276的HIV-1 IN区域。结果：扩增/测序成功率为75.2%，获得255/339条序列。应用1%的截止值，在13个（5.1%）个体中检测到INSTI的主要DRM，但只有1个个体携带核苷酸频率>= 15%的E92 G。然而，140/255（54.9%）的个体具有多态性的附件DRM，主要是在高频率。与此观察，HIV-1亚型的多样性之间的individuals.Conclusions：治疗前HIV-1耐INSTIs是低的研究地点，这支持使用INSTIs在喀麦隆。然而，需要进一步的研究来评估多态性辅助DRMs对基于INSTI的ART方案的影响。
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.