Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study
Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study
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DOI：
10.1016/s2352-3018(20)30340-4
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发表时间：
2021-04-01
期刊：
影响因子：
16.1
通讯作者：
Spreen, William R.
中科院分区：
文献类型：
--
作者：
Orkin, Chloe;Oka, Shinichi;Spreen, William R.
需要更方便、更少频率的治疗来帮助解决与艾滋病毒感染者每日口服艾滋病毒治疗相关的挑战，包括耻辱、药丸负担、药物-食物相互作用和依从性。3期ATLAS和FLAIR研究显示，每4周给药一次的长效卡替拉韦和利匹韦林与标准口服治疗相比，在维持HIV-1成人病毒抑制超过48周方面具有非劣效性。我们提出了96周的findings.Methods FLAIR是一个randoinised，3期，开放标签，多中心的研究在11个国家进行调查是否切换到长效cabotegravir和利匹韦林是非劣效于每日度鲁特韦，阿巴卡韦，拉米夫定在病毒学抑制的成人艾滋病毒感染者-1。未接受过抗逆转录病毒治疗（ART）的受试者接受诱导治疗，每日口服dolutegravir（50 mg），abacavir（600 mg）和lamivudine（300 mg），持续20周。16周后，HIV-1 RNA拷贝数低于50/mL的受试者被随机分配（1：1）继续接受标准治疗方案（标准治疗组），或改为每日口服卡替拉韦30 mg和利匹韦林25 mg，持续至少4周，然后接受长效卡替拉韦400 mg和利匹韦林600 mg，以两次2 inL肌内注射给药，每4周一次，持续至少96周（长效组）。按基线（诱导前）HIV-1 RNA（≥ 100000拷贝/mL）和出生时性别对随机化进行分层，并使用葛兰素史克验证的随机化软件（RandAll NG，版本1.3.3）进行治疗分配。主要终点是根据美国食品药品监督管理局（FDA）快照算法评估的第48周血浆HIV-1 RNA ≥ 50拷贝/mL的受试者比例，之前已报告。在此，我们报告了第96周时使用FDA快照算法检测HIV-1 RNA拷贝数≥ 50/mL的受试者比例（意向治疗人群;非劣效性界值6%）。该试验注册于ClinicalTrials.gov，NCT 02938520。结果在2016年10月27日至2017年3月24日期间，筛选了809名参与者。631名（78%）参与者进入诱导阶段，566名（70%）被随机分配到标准治疗组（283名[50%]参与者）或长效组（283名[50%]）。中位年龄为34岁（IQR 29 - 43），62例（11%）为50岁或以上，127例（22%）为女性（出生时性别），419例（74%）为白色。第96周时，每组中有9例（3%）受试者的HIV-1 RNA拷贝数为50或以上/mL，校正差异为0.0（9S%CI-2.9至2.9），与第48周时确定的非劣效性一致。在两个治疗组中，导致退出的不良事件很少发生（长效组有14名[5%]参与者，标准治疗组有4名[1%]参与者）。注射部位反应是最常见的不良事件，长效组有245名（88%）参与者报告;其频率随着时间的推移而下降。中位注射部位反应持续时间为3天（IQR 2 - 4），3100例反应中有3082例（99%）为1级或2级。解释96周的结果再次证实了48周的结果，表明长效cabotegravir和利匹韦林在维持HIV-1成人患者的病毒抑制方面与继续标准治疗方案相比仍然具有非劣效性。这些结果支持长效cabotegravir和利匹韦林在近2年的时间内作为病毒抑制的HIV-1成人治疗选择的持久性。版权所有（C）2021爱思唯尔有限公司保留所有权利。
Background There is a need for more convenient, less frequent treatment to help address challenges associated with daily oral HIV treatment in people living with HIV, including stigma, pill burden, drug-food interactions, and adherence. The phase 3 ATLAS and FLAIR studies showed non-inferiority of long-acting cabotegravir and rilpivirine dosed every 4 weeks compared with standard oral therapy for the maintenance of virological suppression in adults with HIV-1 over 48 weeks. We present the 96-week findings.Methods FLAIR is a randoinised, phase 3, open-label, multicentre study done in 11 countries investigating whether switching to long-acting cabotegravir and rilpivirine is non-inferior to daily dolutegravir, abacavir, and lamivudine in virologically suppressed adults living with HIV-1. Antiretroviral therapy (ART)-naive participants received induction therapy with daily oral dolutegravir (50 mg), abacavir (600 mg), and lamivudine (300 mg) for 20 weeks. After 16 weeks, participants with less than 50 HIV-1 RNA copies per mL were randomly assigned (1:1) to continue the standard of care regimen (standard care group) or switch to receive daily oral cabotegravir 30 mg and rilpivirine 25 mg for at least 4 weeks followed by long-acting cabotegravir 400 mg and rilpivirine 600 mg, administered as two 2 inL intramuscular injections, every 4 weeks for at least 96 weeks (long-acting group). Randomisation was stratified by baseline (preinduction) HIV-1 RNA (= 100000 copies per mL) and sex at birth and used GlaxoSmithKline-verified randomisation software (RandAll NG, version 1.3.3) for treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per tnL or more assessed as per the US Food and Drug Adininistration (FDA) Snapshot algorithm at week 48, which has been reported previously. Here, we report the proportion of participants with 50 or more HIV-1 RNA copies per mL using the FDA Snapshot algorithm at week 96 (intention-to-treat population; non-inferiority margin 6%). The trial is registered with ClinicalTrials.gov, NCT02938520.Findings Between Oct 27, 2016, and March 24, 2017, 809 participants were screened. 631 (78%) participants entered the induction phase and 566 (70%) were randomly assigned to either the standard care group (283 [50%] participants) or the long-acting group (283 [50%]). Median age was 34 years (IQR 29 to 43), 62 (11%) were 50 years or older, 127 (22%) were women (sex at birth), and 419 (74%) were white. At week 96, nine (3%) participants in each arm had 50 or more HIV-1 RNA copies per mL, with an adjusted difference of 0.0 (9S% CI -2.9 to 2.9), consistent with non-inferiority established at week 48. Across both treatment groups, adverse events leading to withdrawal were infrequent (14[5%] participants in the long-acting group and four [1%] in the standard care group). Injection site reactions were the most common adverse event, reported by 245 (88%) participants in the long-acting group; their frequency decreased over time. Median injection site reaction duration was 3 days (IQR 2 to 4), and 3082 (99%) of 3100 reactions were grade 1 or 2. No deaths occurred during the maintenance phase.Interpretation The 96-week results reaffirm the 48-week results, showing long-acting cabotegravir and rilpivirine continued to be non-inferior compared with continuing a standard care regimen in adults with HIV-1 for the maintenance of viral suppression. These results support the durability of long-acting cabotegravir and rilpivirine, over an almost 2-year-long period, as a therapeutic option for virally suppressed adults with HIV-1. Copyright (C) 2021 Elsevier Ltd. All rights reserved.