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《柳叶刀》(The Lancet)发表一项随机、开放标签的3期临床试验,旨在评估比克替拉韦-来那帕韦(bictegravir–lenacapavir)这一新型复方单片疗法在HIV-1感染者中的有效性和安全性。研究发现,对于正在采用复杂用药方案且达到病毒学抑制的HIV-1感染者,转为每日一次口服比克替拉韦-来那帕韦复方单片在维持病毒抑制方面非劣效于继续使用原有复杂用药方案,且未出现耐药情况,安全性特征相似。识别文中二维码或点击文末阅读原文,查阅原文。

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《柳叶刀》(The Lancet发表的一项3期临床试验结果显示,新型每日口服复方单片BIC/LEN将比克替拉韦(bictegravir)和来那帕韦(lenacapavir)这两种现有HIV治疗药物进行结合,或能有效替代长期存活HIV感染者目前使用的复杂多片剂治疗方案。

本项试验纳入了来自15个国家的550余名HIV感染者,结果表明新型复方单片疗法在维持HIV抑制(HIV病毒载量低于50拷贝/毫升)方面效果显著。近96%转用这种简化疗法的受试者维持了病毒抑制水平,且未报告新发耐药情况。相比之下,继续使用原有复杂多片剂用药方案的受试者显示出相似疗效,病毒抑制维持率约为94-96%。

受试者中位年龄为60岁(年龄范围在22~84岁之间),明显高于HIV药物试验通常纳入人群的年龄水平。多数受试者此前每日需服用的抗艾滋病药物剂量为2~11片,其中约40%的受试者每日需服用抗逆转录病毒药物超过一次。此外,许多受试者还报告了其他健康问题,如心血管疾病或肾脏疾病,且多数对先前的HIV治疗已产生耐药性。

在该研究期间,未发现任何重大或新发安全性问题,且多数受试者的血脂相关副作用(如胆固醇水平升高)较之前有所减少,或能为心脏病风险人群带来潜在的额外获益。

受试者反馈称,这种新的治疗方案更简便易行,有助于提升患者每日坚持用药的依从性。研究作者指出,这一点对于老年HIV感染者、既往对HIV治疗产生了耐药性的人群,以及在服用HIV药物同时还需额外用药管理年龄相关健康问题的人群而言尤为重要。

目前正在开展进一步的临床试验,以验证BIC/LEN复方单片的长期安全性和有效性。

文章摘要

从复杂HIV治疗方案转为比克替拉韦-来那帕韦单片疗法(ARTISTRY-1):一项随机、开放标签的3期临床试验

背景
复方单片(Single-tablet regimens, STRs)革新了HIV-1的治疗,提高了患者的用药依从性和治疗效果;然而,由于耐药性、禁忌症或药物间相互作用等原因,许多患者无法采用目前的复方单片治疗,只能依赖复杂的多片剂方案。因此,目前亟需研发新型复方单片治疗方案。本研究旨在评估比克替拉韦-来那帕韦这一新型复方单片疗法在HIV-1感染者中的有效性和安全性。

方法
ARTISTRY-1是一项随机、开放标签、阳性药物对照、非劣效性3期试验,在15个国家的医院和诊所中展开,研究对象为正在采用复杂用药方案且达到病毒学抑制的HIV-1感染者。受试者按地理区域分层并按照2:1的比例通过交互技术进行随机分配,转为每日一次口服比克替拉韦-来那帕韦75mg/50mg单片方案,或继续采用原有复杂用药方案。研究主要结局是在所有接受了至少一剂指定治疗的受试者中评估第48周时HIV-1 RNA病毒载量达到或超过50拷贝/毫升的受试者比例(采用美国食品药品监督管理局快照算法)。本试验(进行中;入组已完成)已在ClinicalTrials.gov注册(编号NCT05502341)。

结果
在2024年1月29日至9月26日期间,共对729名受试者进行了筛选,其中557人经随机分配接受治疗(比克替拉韦-来那帕韦组371人;复杂用药方案组186人)。基线时,受试者中位年龄为60岁(年龄范围22~84岁),HIV治疗时长为28年(四分位距22~32年);受试者每日服用抗逆转录病毒药物中位数为3片(范围2~11片)。在第48周,比克替拉韦-来那帕韦组有3名(1%)受试者、复杂用药方案组有2名(1%)观察到HIV-1 RNA病毒载量达到或超过50拷贝/毫升(差值-0.3%;95.002%置信区间为-2.3~1.8),达到4%的非劣效性界值。未出现耐药情况。两组不良事件发生率相似。比克替拉韦-来那帕韦组有6名(2%)受试者、复杂用药方案组有1名(1%)受试者因不良事件中止治疗。比克替拉韦-来那帕韦组出现5例死亡,经判断均与研究药物无关。受试者转为比克替拉韦-来那帕韦方案后所报告的治疗满意度有所提高。

解释
比克替拉韦-来那帕韦复方单片在疗效上非劣效于复杂用药方案,安全性特征相似,且治疗满意度更高。比克替拉韦-来那帕韦复方单片疗法为正在采用复杂用药方案的HIV-1感染者提供了优化治疗方案的新选择。END

Funding
Gilead Sciences.

Declaration of interests

CO received grants (paid to her institution) from Gilead Sciences, MSD, and ViiV Healthcare; received consulting fees for advisory boards and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Bavarian Nordic, Gilead Sciences, GSK, MSD, and ViiV Healthcare; received support for attending meetings and/or travel from Bavarian Nordic, Gilead Sciences, and ViiV Healthcare; and is a governing council member of the International AIDS Society (unpaid). PJR received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare. MH received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and support for attending meetings and/or travel from, and participated on advisory boards for, Gilead Sciences, Merck, and ViiV Healthcare. CG received consulting fees from Gilead Sciences, Merck, and ViiV Healthcare; and received payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare. MHL received research grants (paid to his institution) from Gilead Sciences, and participated on advisory boards for Gilead Sciences and ViiV Healthcare. BT received consulting fees, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and support for attending meetings and/or travel, from Gilead Sciences and ViiV Healthcare. TL received grants or contracts from AbbVie, Charité Berlin, Deutsche Leberstiftung, Gilead Sciences, GSK/ViiV Healthcare, Immuno Therapeutics Heidelberg, Janssen, Moderna, and MSD. MO received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences; received support for attending meetings and/or travel from Gilead Sciences, Janssen, and ViiV Healthcare; participated on a data safety monitoring or advisory board for Gilead Sciences; and is an unpaid member of ASHM Board and Australian ARV Guidelines Committee. MB received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences, GSK, and ViiV Healthcare; received support for attending meetings and/or travel from Gilead Sciences and ViiV Healthcare; and participated on data safety monitoring or advisory boards for Gilead Sciences, GSK, and ViiV Healthcare. JS received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences, Merck, Thera, and ViiV Healthcare. MRa received consulting fees from Gilead Sciences, Shionogi, and ViiV Healthcare; and received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Gilead Sciences, and ViiV Healthcare. SS received research grants and support for clinical trials (paid to her institution) from Janssen, Merck, and the South African Medical Research Council; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from ViiV Healthcare; received support for attending meetings and/or travel from Merck; received a drug donation to her institution from ViiV Healthcare; and participated on an advisory board for AbbVie. KM received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from, and served on an advisory board for, Epividian, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. H-CT received honoraria for a lecture at an international congress, and travel and registration support for attending an international meeting, from Gilead Sciences. JSB received research grants or contracts from Chem Bio Diagnostics, Gilead Sciences, and Moderna; and consulting fees and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie. XZ, KA, KP, NM, JMM-R, PS, and MRh are employees of Gilead Sciences and own employee stock grants. PC received research grants and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from ViiV Healthcare; and consulting fees from Gilead Sciences, Merck, and ViiV Healthcare.



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)00307-7
题图Copyright: Westend61 via Getty Images

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