Efficacy, safety, and pharmacokinetics of lenacapavir oral bridging when subcutaneous lenacapavir cannot be administered.

IF 3.4 2区 医学 Q3 IMMUNOLOGY
AIDS Pub Date : 2025-05-01 Epub Date: 2025-02-10 DOI:10.1097/QAD.0000000000004142
Onyema E Ogbuagu, Anchalee Avihingsanon, Sorana Segal-Maurer, Hui Wang, Vamshi K Jogiraju, Renu Singh, Martin S Rhee, Hadas Dvory-Sobol, Peter A Sklar, Jean-Michel Molina
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引用次数: 0

Abstract

Objective: To assess efficacy, safety and pharmacokinetics (PK) of oral lenacapavir (LEN) when used as oral bridging (OB) between delayed subcutaneous (SC) LEN injections.

Design: Post-hoc analysis of participants in two clinical trials of SC LEN for HIV-1 treatment who required OB when LEN SC dosing was interrupted.

Methods: Oral LEN [300 mg once weekly (QW)] was initiated within 2 weeks of the next scheduled injection (dosing interval: 26 weeks). Efficacy, safety, and PK were assessed every 10-12 weeks.

Results: Overall, 139 participants received ≥1 dose of oral 300 mg QW LEN plus other antiretrovirals. Median duration of OB was 19 weeks in both clinical trials. By missing = excluded analysis, over 95% of participants maintained virologic suppression (HIV-1 RNA <50 copies/mL) at Weeks 10, 20, and 30. Treatment-emergent AEs (TEAEs) were similar to those with SC LEN (excluding injection site reactions). No Grade ≥3 or serious TEAEs were considered related to oral LEN. Throughout OB, mean LEN plasma concentrations and lower bound of 90% confidence intervals (CIs) were consistently above inhibitory quotient 4 (4-fold in-vitro protein binding-adjusted 95% effective concentration). OB adherence (by pill count) was ≥95% in the majority of participants in both clinical trials.

Conclusions: High rates of virological suppression were maintained during OB. Oral 300 mg QW LEN was well tolerated and provided adequate plasma concentrations to bridge SC LEN dosing. This analysis supports using 300 mg QW LEN for OB when SC LEN treatment is interrupted.

当不能皮下给药时,来那卡韦口服桥接的有效性、安全性和药代动力学。
目的:评价口服来那卡帕韦(lenacapavir, LEN)作为延迟皮下注射lenacapavir之间的口服桥接(OB)的有效性、安全性和药代动力学(PK)。设计:对两项临床试验中使用SC LEN治疗HIV-1的参与者进行事后分析,这些参与者在LEN SC剂量中断时需要OB。方法:口服LEN [300 mg,每周一次(QW)]在下一次预定注射后2周内开始(给药间隔:26周)。每10-12周评估一次疗效、安全性和PK。结果:总体而言,139名参与者接受了≥1剂量的口服300 mg QW LEN和其他抗逆转录病毒药物。在两项临床试验中,OB的中位持续时间为19周。通过缺失=排除分析,超过95%的参与者维持了病毒学抑制(HIV-1 RNA)。结论:OB期间维持了高病毒学抑制率。口服300 mg QW LEN耐受性良好,并提供足够的血浆浓度来桥接SC LEN剂量。该分析支持在SC LEN治疗中断时使用300 mg QW LEN治疗OB。
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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来源期刊
AIDS
AIDS 医学-病毒学
CiteScore
5.90
自引率
5.30%
发文量
478
审稿时长
3 months
期刊介绍: ​​​​​​​​​​​​​​​​​Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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