Outcomes of switching from protease inhibitor-based antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed adults with nucleos(t)ide analogue resistance- a phase IV randomised, open-label study (PIBIK study).
Collins Iwuji, Laura Waters, Ana Milinkovic, Chloe Orkin, Julie Fox, Frank Post, Nicky Perry, Chloe Bruce, Natalie Dailey, Ye To, Stephen Bremner, Duncan Churchill, Anna Maria Geretti
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引用次数: 0
Abstract
Background: There are limited data on how historical nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs) other than M184V/I, affect the activity of B/F/TAF. We evaluated the outcomes of switching virologically suppressed (HIV-1 RNA < 50 copies/mL) individuals harbouring major RAMs from boosted protease inhibitor (bPI)-based therapy to B/F/TAF.
Methods: Participants had various historical genotypic patterns including M184V/I, ≤2 thymidine analogue mutations (TAMs), and other NRTI RAMs (NAMs), and no integrase resistance. Baseline RAMs were explored by retrospective sequencing of cellular HIV-1 DNA. Participants were randomised (1:1) to switching to B/F/TAF either immediately or after 24 weeks. The primary outcome was the proportion of participants maintaining virological suppression (pure virologic response) at week-24; secondary outcomes were proportion of participants with virological suppression at week-48, pre-specified safety measures, and treatment-emergent resistance.
Results: Historically, 21/72 (29.2%) participants had M184V/I, 5 (6.9%) M184V/I + 1 NAM, 31 (43.1%) 1 TAM ± M184V/I ± 1 NAM, and 15 (20.8%) 2 TAMs ± M184V/I ± 1 NAM. At week-24, proportions maintaining virological suppression were 33/33 (100%) on B/F/TAF vs. 38/39 (97.4%) on bPI (difference 2.6%; 95% CI -2.4%, 7.5%). Drug-related adverse events (AEs) were reported in 10/33 (30.3%) vs. 1/39 (2.6%), respectively. The immediate switch arm had improved lipid parameters but increased HbA1c and weight. Virological suppression was maintained at week-48. There were six discontinuations; four on B/F/TAF were drug-related and the two on bPI were not drug-related.
Conclusions: Historical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching.
背景：除了M184V/I之外，关于历史核苷逆转录酶抑制剂（NRTI）耐药相关突变（RAMs）如何影响B/F/TAF活性的数据有限。我们评估了转换病毒学抑制（HIV-1 RNA）的结果方法：参与者具有各种历史基因型模式，包括M184V/I，≤2胸腺嘧啶类似物突变（tam）和其他NRTI RAMs (NAMs)，并且没有整合酶抗性。通过细胞HIV-1 DNA的回顾性测序来探索基线RAMs。参与者随机（1:1）立即或在24周后切换到B/F/TAF。主要结局是参与者在第24周保持病毒学抑制（纯病毒学反应）的比例；次要结局是参与者在第48周出现病毒学抑制的比例、预先指定的安全措施和治疗后出现的耐药性。结果：既往有M184V/I 21/72例（29.2%），M184V/I + 1 NAM 5例（6.9%），1 TAM±M184V/I±1 NAM 31例（43.1%），2 TAM±M184V/I±1 NAM 15例（20.8%）。第24周，B/F/TAF维持病毒学抑制的比例为33/33 (100%)，bPI为38/39(97.4%)(差异2.6%；95% ci -2.4%, 7.5%)。药物相关不良事件（ae）分别为10/33（30.3%）和1/39（2.6%）。立即切换组血脂参数改善，但HbA1c和体重增加。病毒学抑制维持在第48周。有六次停刊；B/F/TAF组4例与药物相关，bPI组2例与药物无关。结论：在病毒学抑制的成人中，NRTI的历史耐药并未影响B/F/TAF的有效性。12%的患者在转换后出现治疗限制性ae。注册号：2018-004732-30。
期刊介绍：
Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies.
The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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