BREATHER Plus clinical trial design: A randomised non-inferiority trial evaluating the efficacy, safety and acceptability of short cycle (five days on, two days off) dolutegravir/tenofovir-based triple antiretroviral therapy (ART) compared to daily ART in virologically suppressed adolescents living with HIV aged 12 to <20 years in sub-Saharan Africa

IF 1.9 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary clinical trials Pub Date : 2025-05-29 DOI:10.1016/j.cct.2025.107963

Fredrick Katongole , Tiyara Arumugam , Angus Jennings , Constantine Mutata , Patrick Ssebunya , Charity Wamboi , Alexandra Green , Mutsa Bwakura-Dangarembizi , Cissy Kityo , Abraham Siika , Moherndran Archary , Lungile Jafta , Stella Namukwaya , Janet Seeley , Henry Mugerwa , Simon Walker , Naomi Apoto , Margaret J. Thomason , Deborah Ford , Sarah L. Pett , Eram David Williams

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引用次数: 0

Abstract

Background

Novel strategies to improve ART adherence, retention in care and quality of life among adolescents living with HIV (ALHIV) are needed. Short-Cycle Therapy (SCT) with 4/5 sequential days on ART, 2/3 days off ART per week has shown non-inferior virological outcomes and high acceptability, but most data are in adults and are very limited for dolutegravir (DTG)-based SCT.

Methods

BREATHER Plus is an ongoing 96-week non-inferiority randomised trial evaluating efficacy, safety and acceptability of SCT (5 sequential days on, 2 days off at the weekend) with DTG/tenofovir (TNV)-based triple ART versus continuous (daily) therapy (CT) in ALHIV. Participants are aged 12 to <20 years in Kenya/South Africa/Uganda/Zimbabwe, virologically suppressed (Viral Load (VL) <50copies/mL) for ≥12 months at enrollment, with no prior treatment failure. Randomisation is 1:1 to SCT versus CT. VL monitoring for clinical management is 6–12 monthly aligning with standard-of-care. The primary outcome is confirmed virological rebound ≥50 copies/mL by 96 weeks. The trial employs the Smooth Away From Expected (SAFE) non-inferiority frontier, where the non-inferiority margin depends on the observed event risk in the CT arm. Secondary outcomes include HIV resistance, toxicities, patient-reported outcomes and cost-effectiveness. Enrolment of 470 participants completed in June 2023.

Discussion

BREATHER Plus is the first randomised trial specifically evaluating DTG/TNV-triple based SCT. Rapid roll-out of DTG and a pragmatic approach to VL monitoring mean results will be generalisable to ALHIV across sub-Saharan Africa. If SCT provides non-inferior virological suppression to CT, it may offer choice for ALHIV on how they take their ART.

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BREATHER加临床试验设计：一项随机非劣效性试验，评估短周期（5天服用，2天休息）多替格雷韦/替诺福韦三线抗逆转录病毒治疗（ART）与每日抗逆转录病毒治疗在撒哈拉以南非洲12至<20 岁病毒学抑制的艾滋病毒感染者青少年中的有效性、安全性和可接受性。

背景：需要新的策略来提高艾滋病毒（ALHIV）青少年抗逆转录病毒治疗的依从性、护理坚持性和生活质量。短周期治疗（SCT），连续4/5天抗逆转录病毒治疗，每周2/3 天抗逆转录病毒治疗，显示出不差的病毒学结果和高可接受性，但大多数数据是在成人中，并且基于多替替韦（DTG）的SCT非常有限。方法：BREATHER Plus是一项持续96周的非劣效性随机试验，评估基于DTG/替诺福韦（TNV）的三联抗逆转录病毒治疗（SCT）与持续（每日）治疗（CT）的有效性、安全性和可接受性（连续5天，周末休息2天 ）。讨论：breathe Plus是第一个专门评估基于DTG/ tnv三重的SCT的随机试验。快速推广DTG和对VL监测采取务实的方法，意味着结果将推广到撒哈拉以南非洲的ALHIV。如果SCT对CT具有非劣等的病毒学抑制作用，它可能为ALHIV患者提供如何服用抗逆转录病毒药物的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Contemporary clinical trials 医学-药学

CiteScore

3.70

自引率

4.50%

发文量

281

审稿时长

44 days

期刊介绍： Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.