长效注射用卡替拉韦+利匹韦林用于 HIV 维持治疗：第 3 阶段 ATLAS 和 FLAIR 试验的第 48 周汇总分析。

Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials.

机构信息

Department of Infectious Diseases, Fatebenefratelli Sacco Hospital, Milan, Italy.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

出版信息

J Acquir Immune Defic Syndr. 2020 Dec 1;85(4):498-506. doi: 10.1097/QAI.0000000000002466.

DOI:10.1097/QAI.0000000000002466

PMID:33136751

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7592884/

Abstract

BACKGROUND

Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1.

SETTING

ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies.

METHODS

Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints.

RESULTS

The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm.

CONCLUSION

This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

摘要

背景

长效（LA）注射方案是治疗 HIV-1 感染者的一种潜在治疗选择。

设定

ATLAS（NCT02951052）和 FLAIR（NCT02938520）是两项随机、开放标签、多中心、多国的 3 期研究。

方法

病毒学抑制（血浆 HIV-1 RNA<50 拷贝/mL）的成年参与者被随机（1:1）分配继续接受当前的抗逆转录病毒治疗方案（CAR）或转为长效（LA）卡替拉韦（CAB）和利匹韦林（RPV）方案。在 LA 组，参与者最初接受每日一次的口服 CAB+RPV 治疗 4 周，以评估个体安全性和耐受性，然后开始每月注射治疗。这项联合分析的主要终点是第 48 周的抗病毒疗效（FDA 快照算法：HIV-1 RNA≥50 拷贝/mL 的非劣效性边界为 4%）。次要终点包括安全性、耐受性和确认的病毒学失败（连续 2 次血浆 HIV-1 RNA≥200 拷贝/mL）。

结果

意向治疗暴露人群中每组各有 591 名参与者[28%（出生时性别）为女性，19%年龄≥50 岁]。第 48 周时，主要（HIV-1 RNA≥50 拷贝/mL）和关键次要（HIV-1 RNA<50 拷贝/mL）疗效终点均达到非劣效性标准。每组各有 7 例（1.2%）发生确认的病毒学失败；LA 组有 6/7（6/7）例和 CAR 组有 3/7（3/7）例出现耐药相关突变。大多数 LA 受者（83%）出现注射部位反应，随着时间的推移，其发生率逐渐降低。注射部位反应导致 6 例（1%）参与者退出。每组的严重不良事件发生率为 4%。