杜鲁特格拉维尔
整合酶
养生
埃替拉韦
病毒学
整合酶抑制剂
耐受性
医学
抗药性
桑格测序
突变
遗传学
药理学
生物
人类免疫缺陷病毒(HIV)
抗逆转录病毒疗法
内科学
病毒载量
基因
不利影响
作者
Shimba Henerico,Eric Lyimo,Abel Makubi,Daniel Magesa,Bernard Desderius,Andreas Müeller,John Changalucha,Paul L. A. M. Corstjens,Gert U. van Zyl,Wolfgang Preiser,Stephen E. Mshana,Christa Kasang
摘要
Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs.Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively.No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%).This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.
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