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首页> 外文期刊>EBioMedicine >Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration
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Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

机译：接受世界卫生组织推荐的含替诺福韦一线治疗方案的个体中病毒学衰竭的突变相关性：国际合作

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Abstract Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with {VF} on such a regimen is not known. To identify {TDF} regimen-associated mutations (TRAMs), we compared the proportion of each {RT} mutation in 2873 individuals with {VF} on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-na?ve individuals. To identify {TRAMs} specifically associated with TDF-selection pressure, we compared the proportion of each {TRAM} to its proportion in a cohort of 5805 individuals with {VF} on a first-line thymidine analog-containing regimen. We identified 83 {TRAMs} including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and {Y115F} – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected {TRAMs} will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced {TDF} susceptibility in individuals with {VF} on a TDF-containing regimen.
机译：摘要在WHO推荐的含TDF的一线方案中，由K65R / N和/或K70E / Q / G定义的替诺福韦二富马酸富马酸盐（TDF）基因型耐药发生在20％至60％的病毒学衰竭（VF）患者中。然而，在这种方案下在具有{VF}的个体中选择的逆转录酶（RT）突变的全谱是未知的。为了确定{TDF}方案相关的突变（TRAM），我们比较了WHO建议的含TDF的一线方案中2873名患有{VF}的个体中每个{RT}突变的比例及其在50,803人群中的比例初次使用抗逆转录病毒的人。为了确定与TDF选择压力特别相关的{TRAMs}，我们在包含一线胸腺嘧啶类似物的方案中比较了5805个有{VF}的个体中每个{TRAM}的比例。我们鉴定出83个{TRAM}，包括33个与NRTI相关的，40个与NNRTI相关的以及10个罕见的来源不确定的突变。在33个与NRTI相关的TRAM中，有12个– A62V，K65R / N，S68G / N / D，K70E / Q / T，L74I，V75L和{Y115F} –在接受含一线TDF的人中更常见与一线含胸苷类似物的治疗方案相比。这12个TDF选择的{TRAMs}对于监测与TDF相关的传递的药物耐药性以及确定在含有TDF的方案中患有{VF}的个体中{TDF}易感性降低的程度非常重要。

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