Booster-free Antiretroviral Therapy for Persons Living With HIV and Multidrug Resistance: A Multicentre Multi-stage Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 210
- 试验地点
- 8
- 主要终点
- Loss of viral suppression
研究概览
简要总结
The primary objective of the study is to evaluate the efficacy of a booster-free regimen including DOR/DTG/3TC among HIV-suppressed PLWH with previous virological failure. The key secondary objectives are i) to determine whether switching to DOR / DTG / 3TC leads to lower burden of DDI compared to continuing a booster-containing regimen, and ii) to assess changes in patient perception on treatment acceptability and satisfaction, as well as health-related quality of life after a switch to booster-free ART.
Qualitative sub-study:
Qualitative objectives will be met using semi-structured interviews. Thirty people (15 from the intervention arm, 15 from the control arm) will be interviewed twice, at week 0 and week 48. Additional 15 individuals from the observational cohort will be interviewed once. Interviews will take place following study visits and performed using semi-structured guides. The guide for the interviews at week 48 will be based on results from analyses of the interviews conducted at week 0.
详细描述
Life expectancy of persons living with HIV on antiretroviral therapy (ART) is increasing and drug-drug interactions (DDI) with co-medications are becoming a major concern. Individuals who previously experienced virological failure are at risk of DDI as they are generally treated with ritonavir- or cobicistat-boosted ART. The high potency as well as the favorable safety and pharmacokinetic profile of new antiretroviral drugs, including dolutegravir (DTG) and doravirine (DOR), support their evaluation as part of un-boosted therapy for individuals with a history of virological failure. In this adaptive trial within the Swiss HIV Cohort Study (SHCS) and partner clinics in the Netherlands, the investigators aim to evaluate the efficacy and acceptability of the booster-free regimen DOR/DTG/3TC for treatment-experienced individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Intervention
Doravirine 100 mg (Pifeltro®) will be administered once daily in combination with co-formulated dolutegravir/lamivudine 50/300 mg (Dovato®) for a duration of 48 weeks.
干预措施: DOR/DTG/3TC (Drug)
结局指标
主要结局
Loss of viral suppression
时间窗: Week 48
Difference in the proportion of individuals with an HIV-RNA ≥50 cp/mL at 48 weeks between the treatment arms.
次要结局
- Patient report outcomes concerning changes in treatment satisfaction between baseline and 48 weeks, as determined using the HIV Treatment Satisfaction Questionnaire HIVTSQc (change version).(Week 0 to 48)
- Proportion of patients experiencing confirmed virological failure(Week 48)
- Proportion of individuals detected with new drug resistance(Week 0 to 48)
- Patient report outcomes concerning differences in quality of life between both groups at week 48 assessed by the World Health Organization Quality-of-Life- HIV Bref (WHOQOL-HIV BREF) questionnaire(Week 48)
- Changes in intact proviral HIV-DNA levels(Week 0 to 48)
- Changes in DDI score from week 0 to 48(Week 0 and 48)
- Proportion of individuals reporting depression assessed by Patient Health Questionnaire-9(Week 0 and 48)
- Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI(Week 0 to 48)
- Patient report outcomes concerning differences in treatment satisfaction between both groups assessed by HIV Treatment Satisfaction Questionnaires(Week 48)
- Proportion of individuals who develop a detectable HBV viral load(Weeks 24 and 48)
- Cumulative cost of all ART drugs used(Week 0 to 48)
- Needs regarding the booster-free regimen or regarding ART in general assessed by qualitative interviews in a subset of approximately 30 trial participants(Week 0 and 48)
- Expectations regarding the booster-free regimen or regarding ART in general assessed by qualitative interviews in a subset of approximately 30 trial participants(Week 0 and 48)
- Proportion of patients with DDI leading to suboptimal management of comorbidities(Week 0 and 48)
- Perception of the trial and/or of HIV-related research in general assessed by qualitative interviews in a subset of approximately 30 trial participants(Week 0 and 48)
- Perspectives on how the participants' current and anticipated needs can be assessed by qualitative interviews in a subset of approximately 30 trial participants(Week 0 and 48)
- Acceptability conditions of participation in the trial assessed by qualitative interviews in a subset of approximately 30 trial participants(Week 0 and 48)