Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature

杜鲁特格拉维尔 雷特格韦 恩曲他滨 替诺福韦-阿拉芬酰胺 病毒学 医学 整合酶 阿巴卡韦 整合酶抑制剂 达芦那韦 抗性突变 药理学 病毒载量 生物 逆转录酶 遗传学 人类免疫缺陷病毒(HIV) 基因 抗逆转录病毒疗法 聚合酶链反应
作者
L Buzón,Carolina Navarro-San Francisco,María Fernández-Regueras,Leticia Sanchez-Gomez
出处
期刊:Journal of Antimicrobial Chemotherapy [Oxford University Press]
卷期号:79 (5): 1153-1156 被引量:4
标识
DOI:10.1093/jac/dkae085
摘要

Abstract Objectives The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. Methods Clinical case report and review of the literature. Results A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug–drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL. Conclusions This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.

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