Ogbuagu Onyema E, Avihingsanon Anchalee, Segal-Maurer Sorana, Wang Hui, Jogiraju Vamshi K, Singh Renu, Rhee Martin S, Dvory-Sobol Hadas, Sklar Peter A, Molina Jean-Michel
Yale University School of Medicine, New Haven, CT, USA.
HIV-NAT, Thai Red Cross AIDS Research Centre and Excellence Center in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
AIDS. 2025 May 1;39(6):639-648. doi: 10.1097/QAD.0000000000004142. Epub 2025 Feb 10.
To assess efficacy, safety and pharmacokinetics (PK) of oral lenacapavir (LEN) when used as oral bridging (OB) between delayed subcutaneous (SC) LEN injections.
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.
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.
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.
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.
评估口服来那卡韦（LEN）在延迟皮下注射LEN期间用作口服桥接（OB）时的疗效、安全性和药代动力学（PK）。
对两项皮下注射LEN治疗HIV-1的临床试验参与者进行事后分析，这些参与者在LEN皮下给药中断时需要OB。
在下一次预定注射的2周内开始口服LEN[每周一次（QW），300mg]（给药间隔：26周）。每10-12周评估疗效、安全性和PK。
总体而言，139名参与者接受了≥1剂口服300mg QW LEN加其他抗逆转录病毒药物。两项临床试验中OB的中位持续时间均为19周。通过缺失=排除分析，超过95%的参与者在第10、20和30周时维持病毒学抑制（HIV-1 RNA<50拷贝/mL）。治疗中出现的不良事件（TEAE）与皮下注射LEN时相似（不包括注射部位反应）。没有≥3级或严重的TEAE被认为与口服LEN有关。在整个OB期间，LEN的平均血浆浓度和90%置信区间（CI）的下限始终高于抑制商4（体外蛋白结合调整后的4倍95%有效浓度）。两项临床试验中大多数参与者的OB依从性（通过药丸计数）≥95%。
在OB期间维持了较高的病毒学抑制率。口服300mg QW LEN耐受性良好，并提供了足够的血浆浓度以桥接皮下注射LEN给药。该分析支持在皮下注射LEN治疗中断时使用300mg QW LEN进行OB。
