Katongole Fredrick, Arumugam Tiyara, Jennings Angus, Mutata Constantine, Ssebunya Patrick, Wamboi Charity, Green Alexandra, Bwakura-Dangarembizi Mutsa, Kityo Cissy, Siika Abraham, Archary Moherndran, Jafta Lungile, Namukwaya Stella, Seeley Janet, Mugerwa Henry, Walker Simon, Apoto Naomi, Thomason Margaret J, Ford Deborah, Pett Sarah L, Kekitiinwa Adeodata R
Baylor College of Medicine Children's Foundation, Kampala, Uganda.
Department of Paediatrics and Children Health, King Edward VIII Hospital, Enhancing Care Foundation, University of KwaZulu-Natal, Durban, South Africa.
Contemp Clin Trials. 2025 Aug;155:107963. doi: 10.1016/j.cct.2025.107963. Epub 2025 May 29.
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.
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.
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.
需要新的策略来提高感染艾滋病毒青少年（ALHIV）的抗逆转录病毒治疗（ART）依从性、治疗留存率和生活质量。短周期疗法（SCT），即每周连续4/5天进行ART治疗，2/3天不进行ART治疗，已显示出非劣效的病毒学结果和较高的可接受性，但大多数数据来自成人，基于多替拉韦（DTG）的SCT数据非常有限。
BREATHER Plus是一项正在进行的为期96周的非劣效性随机试验，评估基于DTG/替诺福韦（TNV）的三联ART短周期疗法（周末连续5天治疗，2天休息）与持续（每日）疗法（CT）在ALHIV中的疗效、安全性和可接受性。参与者年龄在12至<20岁之间，来自肯尼亚/南非/乌干达/津巴布韦，入组时病毒学抑制（病毒载量（VL）<50拷贝/mL）≥12个月，且既往无治疗失败史。随机分为SCT组和CT组，比例为1:1。为进行临床管理，VL监测每6 - 12个月进行一次，与标准治疗一致。主要结局是在96周时确认病毒学反弹≥50拷贝/mL。该试验采用远离预期的平滑（SAFE）非劣效前沿，其中非劣效界值取决于CT组观察到的事件风险。次要结局包括HIV耐药性、毒性、患者报告的结局和成本效益。470名参与者的入组工作于2023年6月完成。
BREATHER Plus是首个专门评估基于DTG/TNV三联疗法的SCT的随机试验。DTG的快速推广以及VL监测的务实方法意味着研究结果将适用于撒哈拉以南非洲的ALHIV。如果SCT提供与CT非劣效的病毒学抑制效果，那么它可能为ALHIV提供关于如何接受ART治疗的选择。
