非洲病毒学抑制的成人HIV感染者改用长效卡博特韦和利匹韦林（CARES）：一项随机、多中心、开放标签、非劣效性试验的48周结果

Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial.

作者信息

Kityo Cissy, Mambule Ivan K, Musaazi Joseph, Sokhela Simiso, Mugerwa Henry, Ategeka Gilbert, Cresswell Fiona, Siika Abraham, Kosgei Josphat, Shah Reena, Naidoo Logashvari, Opiyo Kimton, Otike Caroline, Möller Karlien, Kaimal Arvind, Wambui Charity, Van Eygen Veerle, Mohammed Perry, Addo Boateng Fafa, Paton Nicholas I

机构信息

Joint Clinical Research Centre (JCRC), Kampala, Uganda.

Infectious Diseases Institute, Kampala, Uganda.

出版信息

Lancet Infect Dis. 2024 Oct;24(10):1083-1092. doi: 10.1016/S1473-3099(24)00289-5. Epub 2024 May 28.

DOI:10.1016/S1473-3099(24)00289-5

PMID:38821073

Abstract

BACKGROUND

Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa.

METHODS

CARES is a randomised, open-label, non-inferiority trial being conducted at eight sites in Uganda, Kenya, and South Africa. Participants with HIV viral load below 50 copies per mL on oral antiretroviral therapy and no history of virological failure were randomly assigned (1:1; web-based, permuted blocks) to receive cabotegravir (600 mg) and rilpivirine (900 mg) by intramuscular injection every 8 weeks, or to continue oral therapy. Viral load was monitored every 24 weeks. The primary outcome was week 48 viral load below 50 copies per mL, assessed with the Food and Drug Administration snapshot algorithm (non-inferiority margin 10 percentage points) in the intention-to-treat exposed population. This trial is registered with the Pan African Clinical Trials Registry (202104874490818) and is ongoing up to 96 weeks.

FINDINGS

Between Sept 1, 2021, and Aug 31, 2022, we enrolled 512 participants (295 [58%] female; 380 [74%] previous non-nucleoside reverse transcriptase inhibitor exposure). Week 48 viral load was below 50 copies per mL in 246 (96%) of 255 participants in the long-acting therapy group and 250 (97%) of 257 in the oral therapy group (difference -0·8 percentage points; 95% CI -3·7 to 2·3), demonstrating non-inferiority (confirmed in per-protocol analysis). Two participants had virological failure in the long-acting therapy group, both with drug resistance; none had virological failure in the oral therapy group. Adverse events of grade 3 or greater severity occurred in 24 (9%) participants on long-acting therapy and ten (4%) on oral therapy; one participant discontinued long-acting therapy (for injection-site reaction).

INTERPRETATION

Long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programmes.

FUNDING

Janssen.

摘要

背景

长效注射用卡博特韦和rilpivirine已获许可用于资源丰富地区的HIV-1感染个体化治疗。在非洲的治疗项目中，由于人口统计学因素、病毒亚型、既往治疗以及给药和监测方法不同，需要更多证据来支持其使用。本研究的目的是确定在非洲每8周注射一次的长效治疗是否不劣于每日口服治疗。

方法

CARES是一项在乌干达、肯尼亚和南非的8个地点进行的随机、开放标签、非劣效性试验。接受口服抗逆转录病毒治疗且HIV病毒载量低于每毫升50拷贝且无病毒学失败史的参与者被随机分配（1:1；基于网络的置换区组），每8周接受一次卡博特韦（600毫克）和rilpivirine（900毫克）肌肉注射，或继续口服治疗。每24周监测一次病毒载量。主要结局是第48周时病毒载量低于每毫升50拷贝，在意向性治疗暴露人群中采用美国食品药品监督管理局的快照算法进行评估（非劣效性界值为10个百分点）。该试验已在泛非临床试验注册中心注册（202104874490818），正在进行至96周。

结果

在2021年9月1日至2022年8月31日期间，我们招募了512名参与者（295名[58%]为女性；380名[74%]既往有非核苷类逆转录酶抑制剂暴露史）。长效治疗组255名参与者中有246名（96%）第48周病毒载量低于每毫升50拷贝，口服治疗组257名参与者中有250名（97%）（差异为-0.8个百分点；95%置信区间为-3.7至2.3），表明具有非劣效性（在符合方案分析中得到证实）。长效治疗组有2名参与者出现病毒学失败，均伴有耐药；口服治疗组无病毒学失败病例。长效治疗组有24名（9%）参与者发生3级或更严重的不良事件，口服治疗组有10名（4%）；1名参与者停止长效治疗（因注射部位反应）。