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南苏丹地区初治的接受整合酶抑制剂治疗的 HIV-1 整合酶基因分型和多态性分析。

Analysis of HIV-1 integrase genotypes and polymorphisms among integrase inhibitors-based antiretroviral treatment naïve patients in South Sudan.

机构信息

Reference Laboratory of Filovirus, Oswaldo Cruz Institute, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Laboratório de Genética Celular e Molecular, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

出版信息

J Med Virol. 2022 Jul;94(7):3320-3327. doi: 10.1002/jmv.27713. Epub 2022 Mar 26.

Abstract

HIV-1 genetic diversity and drug resistance mutations remain public health challenges especially in regions where treatment is limited. The aim of this study was to characterize the HIV-1 integrase (IN) subtype and the possible occurrence of drug-resistance mutations or polymorphisms in resource-poor settings in South Sudan. Dried blood spots from integrase inhibitor treatment (Integrase strand transfer inhibitor [INSTI]) naïve HIV-1 infected patients were subjected to DNA amplification and direct sequencing of integrase genes. The sequences were interpreted for drug resistance according to the Stanford algorithm and the International AIDS Society-USA guidelines. Phylogenetic analysis revealed that HIV-1 subtype D, C, G, A1, and recombinant forms accounted for 40%, 10%, 13.3%, 23.4%, and 13.3%, respectively. Furthermore, inter-subtype recombinants were interspersed within viral strains sampled in other African countries, highlighting complex transmission dynamics within a mobile host population. A total of 78 of 288 (27%) amino acid IN positions presented at least one polymorphism each. Major INSTI resistance mutations were absent, however, polymorphic accessory mutations at positions M50ILR (26.6%) and L74I (3.3%) were detected. Despite the limited size of the study population, our findings underscore the need for monitoring minor and natural polymorphisms that may influence the outcome of treatment regimens.

摘要

艾滋病毒-1 (HIV-1)的基因多样性和耐药突变仍然是公共卫生领域的挑战,特别是在治疗资源有限的地区。本研究的目的是在南苏丹资源匮乏的地区,描述 HIV-1 整合酶(IN)亚型以及可能出现的耐药突变或多态性。对整合酶抑制剂治疗(整合酶抑制剂 [INSTI])初治的 HIV-1 感染患者的干血斑进行 DNA 扩增和整合酶基因的直接测序。根据斯坦福算法和国际艾滋病协会-美国指南对序列进行耐药性解释。系统发生分析显示,HIV-1 亚型 D、C、G、A1 和重组形式分别占 40%、10%、13.3%、23.4%和 13.3%。此外,在其他非洲国家采样的病毒株中,还存在亚间重组体,突出了在流动宿主群体中复杂的传播动态。在 288 个氨基酸中,共有 78 个 IN 位置至少出现了一个多态性。尽管研究人群规模有限,但我们的发现强调了需要监测可能影响治疗方案结果的次要和自然多态性。

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