CAPELLA 研究第 52 周的入口抑制剂交叉耐药性和来那卡韦耐药性。

IF 1.3 4区 医学 Q4 INFECTIOUS DISEASES
Nicolas Margot, Nina Pennetzdorfer, Vidula Naik, Martin Rhee, Christian Callebaut
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引用次数: 0

摘要

背景:来那卡韦(LEN)是第一类人类免疫缺陷病毒1型(HIV-1)衣壳功能抑制剂,用于治疗存在多药耐药性的重度治疗经验HIV感染者(PWH),并与优化背景方案(OBR)联合使用。在此,我们描述了在体外分析2/3期CAPELLA研究中72名参与者样本中入口抑制剂(EI;恩夫韦地、福斯替沙韦、伊巴利珠单抗和马拉韦罗)敏感性和LEN敏感性之间的相互作用,以及CAPELLA在52周内出现耐药性的情况:方法:使用入口检测法分析了参与者筛选样本对 EIs 的表型药敏性,并生成了对 LEN 的药敏性。对第 52 周之前出现病毒学失败的受试者的基因型和表型对 LEN 的耐药性进行了评估:总体而言,对 EIs 产生耐药性的病毒对 LEN 没有交叉耐药性,与野生型相比的平均折叠变化接近 1.0。在第 52 周耐药性分析的 22 名参与者中,9 名参与者(13%)出现了囊膜耐药性突变,其余 13 名参与者(18%)的囊膜序列没有变化:结论:耐 EI 分离物的 gag 序列不会影响 LEN 的敏感性。耐抗逆转录病毒药物的分离株对 LEN 没有交叉耐药性,这支持了在 PWH 中使用 LEN,无论其治疗史如何。在CAPELLA研究的后半年期间,LEN耐药性的产生非常罕见,总体上与功能性LEN单药治疗有关,原因是不坚持治疗或对OBR产生耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.

Background: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.

Methods: The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52.

Results: Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence.

Conclusion: The gag sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.

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来源期刊
Antiviral Therapy
Antiviral Therapy 医学-病毒学
CiteScore
2.60
自引率
8.30%
发文量
35
审稿时长
4-8 weeks
期刊介绍: Antiviral Therapy (an official publication of the International Society of Antiviral Research) is an international, peer-reviewed journal devoted to publishing articles on the clinical development and use of antiviral agents and vaccines, and the treatment of all viral diseases. Antiviral Therapy is one of the leading journals in virology and infectious diseases. The journal is comprehensive, and publishes articles concerning all clinical aspects of antiviral therapy. It features editorials, original research papers, specially commissioned review articles, letters and book reviews. The journal is aimed at physicians and specialists interested in clinical and basic research.
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