柳叶刀 | 从“每日一次”到“每周一次”，HIV治疗或迎来新选择

发布时间：2026-08-18来源：柳叶刀TheLancet

《柳叶刀》（The Lancet）发表一项多中心III期非劣效性试验，旨在评估病毒学抑制状态的HIV-1成年感染者，由每日口服标准治疗转换为每周一次口服islatravir–lenacapavir后的有效性和安全性。结果表明，在第48周时，每周一次方案的疗效非劣效于每日标准治疗，且总体耐受性良好。研究提示，该方案有望成为首个用于HIV-1治疗的每周一次完整口服单片治疗方案。识别文中二维码或点击文末阅读原文，查阅原文。

文章摘要

HIV-1感染者由每日标准治疗转换为每周一次单片islatravir–lenacapavir治疗（ISLEND-2）：一项多中心、随机、开放标签、阳性对照、Ⅲ期非劣效性试验

背景

长间隔给药的抗逆转录病毒治疗方案，有望改善HIV-1感染者的病毒学结局和治疗满意度。本文报告ISLEND-2试验第48周时的主要终点结果。ISLEND-2是一项Ⅲ期试验，旨在评估病毒学抑制状态的HIV-1成年感染者由每日口服标准治疗转换为每周一次口服islatravir–lenacapavir后的有效性和安全性。

方法

本研究是一项随机、开放标签、阳性对照、Ⅲ期非劣效性试验，在14个国家和地区的100个研究中心开展。符合条件的受试者为18岁及以上成年HIV-1感染者，已接受每日口服标准治疗至少6个月并维持病毒学抑制，且既往无病毒学失败史。受试者采用交互式应答技术（interactive response technology, IRT）以1:1的比例随机分组，并按地理区域、抗逆转录病毒药物类别和CD4+ T细胞计数进行分层，转换为每周一次口服单片islatravir（2 mg）–lenacapavir（300 mg）方案，或继续每日口服标准治疗至少96周。主要终点为第48周HIV-1 RNA病毒载量≥50 copies/mL的受试者比例，根据美国食品药品监督管理局定义的Snapshot算法评估，非劣效性界值为4%；在所有经随机分组且至少接受1剂所分配治疗的受试者中进行分析。本试验已在ClinicalTrials.gov注册，注册号为NCT06630299，目前研究仍在进行中，但已停止招募新受试者。

结果

2024年10月8日至2025年4月30日期间，共筛查727名受试者，其中647名符合入组条件，634名完成随机分组，626名接受治疗：314名接受islatravir–lenacapavir治疗，312名接受标准治疗。在626名受试者中，211名（34%）为女性，193名（31%）为黑人，119名（19%）为亚洲人，123名（20%）为西班牙裔或拉丁裔，89名（14%）年龄为65岁及以上。基线时，552名（88%）受试者正在接受单片抗逆转录病毒治疗方案，478名（76%）正在接受含整合酶链转移抑制剂（INSTI）的治疗方案。第48周时，islatravir–lenacapavir组314名受试者中有1名（0.3%）HIV-1 RNA病毒载量≥50 copies/mL，标准治疗组312名受试者中有4名（1.3%）达到该水平（组间差异为-1.0%［95.002% CI −3.0至1.1］），满足非劣效性判定标准。islatravir–lenacapavir组和标准治疗组分别有58名（58/314，18%）和1名（1/312，<1%）受试者发生治疗相关不良事件。islatravir–lenacapavir组314名受试者中有2名（1%）因不良事件退出研究，标准治疗组312名受试者中有1名（<1%）因不良事件退出研究。islatravir–lenacapavir组和标准治疗组分别有24名（8%）和28名（9%）受试者发生3级及以上不良事件，分别有22名（7%）和27名（9%）受试者发生严重不良事件。islatravir–lenacapavir组和标准治疗组分别有1例和2例死亡，经评估均认为与治疗无关。

解释

每周一次islatravir–lenacapavir方案的疗效非劣效于每日标准治疗，且总体耐受性良好。更长期的安全性数据将有助于进一步评估第48周以后该方案的安全性。Islatravir–lenacapavir有望成为首个用于HIV-1治疗的每周一次完整口服单片治疗方案。END

Funding

Gilead Sciences and Merck Sharp & Dohme.

Declaration of interests

AEC received honoraria for speakers bureaus and support for attending meetings and/or travel from Gilead Sciences, and payments (paid to their institution) for industry-sponsored clinical trials from Gilead Sciences and Merck. PNK participated on data safety monitoring boards or advisory boards for Gilead Sciences, Merck, and ViiV Healthcare; received grants or contracts (paid to their institution) from Gilead Sciences, Merck, Theratechnologies, and ViiV Healthcare; received payments (paid to their institution) for industry-sponsored clinical trials from Merck; and holds stock or stock options in Gilead Sciences, Johnson & Johnson, Merck, Moderna, Pfizer, Theratechnologies, and ViiV Healthcare. PJR received honoraria for speakers bureaus from Gilead Sciences and ViiV Healthcare. AL received payments (paid to their institution) for industry-sponsored clinical trials from GSK and MSD. RGN received payments (paid to their institution) for industry sponsored clinical trials from GSK, Merck, and ViiV Healthcare; and is President of the Infectious Diseases Society of America. AA-P received payment for advisory board participation from ViiV Healthcare. FAP received support for attending meetings and/or travel from Gilead Sciences and MSD; and payments (paid to their institution) for industry sponsored clinical trials from Gilead Sciences, Immunocore, Merck, and ViiV Healthcare. DAB received payment (paid to their institution) for industry-sponsored clinical trials and honoraria for presentations from ViiV Healthcare. PCa received research grants (paid to their institution) from ViiV Healthcare; consulting fees from Gilead Sciences, Merck, and ViiV Healthcare; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ViiV Healthcare. EH received payments (paid to their institution) for attending meetings and/or travel from AstraZeneca and Gilead Sciences. DW received grants for clinical trials (paid to their institution) from AbbVie, CMIC, Gilead Sciences, GSK, MSD, and ViiV Healthcare; and honoraria for lectures, presentations, speakers bureaus, or educational events from Gilead Sciences, MSD, Shionogi, and ViiV Healthcare. P-LL received payments for presentations and support for attending meetings from Gilead Sciences and GSK. AHER received payment (paid to their institution) for industry-sponsored clinical trials from Gilead Sciences. MP received honoraria for presentations from AbbVie, Gilead Sciences, Janssen, MSD, Pfizer, and ViiV Healthcare. HW, FS, HD-S, and MR are employees and shareholders of Gilead Sciences, Foster City, CA, USA. KC, MS, and CL are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA, and shareholders of Merck & Co, Rahway, NJ, USA. DS is an employee and shareholder of Gilead Sciences, Foster City, CA, USA; and is also co-chair of the International AIDS Society’s Towards an HIV Cure: Industry Collaborative Group, a board member of the San Francisco AIDS Foundation, and an advisory council member of the California HIV/AIDS Research Program. OO received consulting fees from Gilead Sciences, Merck, and ViiV Healthcare; and honoraria for lectures and support to attend meetings and/or travel from Gilead Sciences. PCh and WR declare no competing interests.

中文翻译仅供参考，所有内容以英文原文为准。

DOI: 10.1016/S0140-6736(26)01442-X