Real-world prevalence of non-integrase INSTI resistance-associated mutations and virological outcomes in people who have recently acquired HIV-1 in the UK.

Christine Kelly,James S Lester,Daniel Bradshaw,David F Bibby,Hodan Mohamed,Gary Murphy,Alison Brown,Caroline Sabin,Anna-Maria Geretti,Jean L Mbisa
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Abstract

INTRODUCTION Integrase strand transfer inhibitors(INSTIs) are the mainstay of antiretroviral therapy(ART) globally. Virological breakthrough is uncommon but often manifests as low level viraemia and only 50% of cases have identified drug resistance mutations in the integrase gene. Non-integrase mutations in the Gag-nucleocapsid protein (NC), envelope glycoprotein (Env) and 3'polypurine tract (3'PPT) have been identified in vitro. METHODS Between 2015 and 2021, HIV-1 whole genome sequencing was performed on samples from people with recently acquired HIV-1 in the UK. Sequences were linked to demographic and clinical data within the UK Health Security Agency's HIV and AIDS Reporting System. The relationship between non-integrase enzyme mutations and virological outcomes was assessed.375 (34%) of 1106 participants started an INSTI-based regimen. Of these, 337 (90%) were men and 196 (52%) were living with subtype B. The median age was 33 years and number of viral loads within 24 months of starting ART was 4. RESULTS Overall, Env Y61H (33, 10%) and A539V (16, 5.0%), 3'PPT c9053t (17, 5.0%), and NC N8S (16, 4.8%) were the most prevalent non-integrase enzyme mutations. Univariable and multivariable Cox regression did not identify significant associations between the presence of these mutations individually and time to viral suppression, or to viral blip. Interestingly, accessory INSTI mutations were found significantly more frequently in people whose virus also harboured the Env mutation A539V (p=0.002). CONCLUSION Several non-integrase mutations were prevalent, but we found no evidence of an impact upon virological outcomes within treatment-naïve individuals on INSTI-based regimens who had recently acquired HIV.
在英国最近获得HIV-1的人群中,非整合酶INSTI耐药相关突变的真实患病率和病毒学结果。
整合酶链转移抑制剂(insis)是全球抗逆转录病毒治疗(ART)的支柱。病毒学上的突破并不常见,但通常表现为低水平的病毒血症,只有50%的病例在整合酶基因中发现了耐药性突变。在体外鉴定了gag -核衣壳蛋白(NC)、包膜糖蛋白(Env)和3′多嘌呤道(3′ppt)的非整合酶突变。方法在2015年至2021年期间,对英国近期感染HIV-1的人的样本进行HIV-1全基因组测序。这些序列与英国卫生安全局的艾滋病毒和艾滋病报告系统中的人口统计和临床数据相关联。非整合酶突变与病毒学结果之间的关系被评估(34%)的1106名参与者开始了基于isi的方案。其中,337例(90%)为男性,196例(52%)为b亚型患者。中位年龄为33岁,开始抗逆转录病毒治疗后24个月内的病毒载量为4。结果总体而言,Env Y61H(33.10%)、A539V(16.5.0%)、3’ppt c9053t(17.5.0%)和NC N8S(16.4.8%)是最常见的非整合酶基因突变。单变量和多变量Cox回归没有发现这些突变单独存在与病毒抑制时间或病毒突变之间的显著关联。有趣的是,在携带Env突变A539V的人群中,发现辅助INSTI突变的频率明显更高(p=0.002)。结论几种非整合酶突变是普遍存在的,但我们没有发现证据表明在最近感染艾滋病毒的treatment-naïve个体中使用基于insi的方案对病毒学结果有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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