Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen

Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen
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DOI:
10.1089/aid.2020.0021
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发表时间:
2020-04-06
影响因子:
1.5
通讯作者:
Ueno, Takamasa
Ueno, Takamasa
中科院分区:
医学4区
文献类型:
--
作者:
Masoud, Salim;Kamori, Doreen;Ueno, Takamasa

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坦桑尼亚最近调整了世界卫生组织的抗逆转录病毒指南,将整合酶链转移抑制剂纳入一线治疗方案。然而,在坦桑尼亚流行的病毒株中缺乏整合酶(IN)基因多态性的证据。在这项研究中,我们描述了在引入inis之前在坦桑尼亚达累斯萨拉姆流行的病毒株的In基因多态性。从158名hiv -1感染者中制备血浆病毒rna,其中包括111名接受治疗但病毒血症(insi -naive)的受试者。将pol基因中包含in编码区的部分扩增出来,用Sanger测序法直接测序。亚型分析显示A1、C、D亚型和亚型间重组分别占42%、38%、11%和9%。虽然多个亚型共循环,但IN基因表现出相对保守的氨基酸序列模式,平均香农熵值为0.16。未发现主要的INSTI耐药突变;5%的受试者在T97A、E157Q、G163E/K和128A/T位点检测到辅助抗性突变。
Tanzania has recently adapted World Health Organization antiretroviral guidelines that include integrase strand transfer inhibitors (INSTIs) in the first-line regimen. However, there is lack of evidence on integrase (IN) gene polymorphisms in viral strains circulating in Tanzania. In this study, we characterize IN gene polymorphisms in viral strains circulating in Dar es Salaam, Tanzania, before introduction of INSTIs. Plasma viral RNAs were prepared from 158 HIV-1-infected subjects, including 111 treated, but viremic (INSTI-naive), subjects. A part of the pol gene encompassing the IN-coding region was amplified and directly sequenced by the Sanger sequencing method. Subtype analysis revealed that subtypes A1, C, and D and intersubtype recombinants were 42%, 38%, 11%, and 9%, respectively. Although multiple subtypes cocirculate, the IN gene exhibited a relatively conserved amino acid sequence pattern with an average Shannon entropy score of 0.16. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects.