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美国阿拉巴马大学伯明翰分校Edgar T Overton团队比较了Cabotegravir和Rilpivirine每2月与每月给药一次治疗HIV患者的疗效和安全性。2020年12月9日，该研究发表在《柳叶刀》杂志上。

3期临床研究显示每4周肌肉注射Cabotegravir和Rilpivirine的长效疗法不逊于口服抗逆转录病毒治疗。2期临床结果以及支持性建模表明每8周给药一次可能为患者提供更大的便利。

为了比较每8周一次和每4周一次肌注Cabotegravir和Rilpivirine，治疗48周后的疗效，研究组在澳大利亚、阿根廷、加拿大、法国、德国、意大利、墨西哥、俄罗斯、南非、韩国、西班牙、瑞典和美国等13个国家进行了一项随机、多中心、开放标签临床3b期试验。

2017年10月27日至2018年5月31日，研究组招募了1149例先前接受过标准口服治疗的HIV成人患者，将1045例随机分组，其中522例接受每8周肌肉注射一次cabotegravir 600 mg + rilpivirine 900 mg，523例接受每4周肌肉注射一次cabotegravir 400 mg + rilpivirine 600 mg，均治疗52周。第48周的主要终点是HIV-1 RNA≥50拷贝/ mL。

参与者的中位年龄为42岁，女性占27％，73％为白人。每8周长效给药组主要终点发生率为2%，不逊于每4周长效给药组（1%）。每8周长效给药组中有8例患者治疗后病毒学失败（两次连续测量结果≥200拷贝/ mL），每4周长效给药组中有2例。

在每8周长效给药组中，基线检查时8例非核苷逆转录酶抑制剂耐药患者中有5例（63%）发现与rilpivirine相关的突变。各给药组之间的安全性相似，在1045名参与者中有844名（81％）出现不良事件（不包括注射部位反应），未发生与治疗相关的死亡。

总之，Cabotegravir和Rilpivirine每8周一次和每4周一次给药治疗HIV患者的疗效和安全性相差不大。

附：英文原文

Title: Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study

Author: Edgar T Overton, Gary Richmond, Giuliano Rizzardini, Hans Jaeger, Catherine Orrell, Firaya Nagimova, Fritz Bredeek, Miguel García Deltoro, Susan Swindells, Jaime Federico Andrade-Villanueva, Alexander Wong, Marie-Aude Khuong-Josses, Rodica Van Solingen-Ristea, Veerle van Eygen, Herta Crauwels, Susan Ford, Christine Talarico, Paul Benn, Yuanyuan Wang, Krischan J Hudson, Vasiliki Chounta, Amy Cutrell, Parul Patel, Mark Shaefer, David A Margolis, Kimberly Y Smith, Simon Vanveggel, William Spreen

Issue&Volume: 2020-12-09

Abstract:

Background

Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing.

Methods

ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing.

Findings

Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34–50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI 0·6–2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred.

Interpretation

The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1.

DOI: 10.1016/S0140-6736(20)32666-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32666-0/fulltext

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