B-free Multistage Trial
- Conditions
- HIVDrug ResistanceDrug Drug Interaction
- Interventions
- Drug: DOR/DTG/3TC
- Registration Number
- NCT06037564
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention DOR/DTG/3TC 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.
- Primary Outcome Measures
Name Time Method Loss of viral suppression Week 48 Difference in the proportion of individuals with an HIV-RNA ≥50 cp/mL at 48 weeks between the treatment arms.
- Secondary Outcome Measures
Name Time Method 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 The investigators will assess changes in treatment satisfaction between week 0 and 48 using the validated HIV Treatment Satisfaction Questionnaire HIVTSQc (change version).
Proportion of patients experiencing confirmed virological failure Week 48 Proportion of patients experiencing confirmed virological failure, defined as 2 consecutive plasma HIV viral loads ≥200 copies/mL
Proportion of individuals detected with new drug resistance Week 0 to 48 Proportion of individuals experiencing impairment / loss of future drug options throughout the study period, defined as new detection of resistance-associated mutations against DOR, DTG, 3TC (intervention-arm) or against the components of the ART regimen that the virus was considered to be sensitive to at randomization (based on historic resistance testing or treatment history; control-arm).
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 Differences in quality of life between both groups at week 48, assessed using the World Health Organization Quality-of-Life- HIV Bref (WHOQOL-HIV BREF) questionnaire
Changes in intact proviral HIV-DNA levels Week 0 to 48 Changes in intact proviral HIV-DNA levels in peripheral blood mononuclear cells (PBMCs) between baseline and week 48. Stored PBMC samples will be used to determine HIV-DNA levels by a digital droplet PCR (ddPCR) assay using the RAINDANCE system.
Changes in DDI score from week 0 to 48 Week 0 and 48 Using the University of Liverpool Drug Database (https://www.hiv-druginteractions.org/), the prescribed ART and co-medications will be categorized as red flag (3 points) for severe DDIs when co-administration is contraindicated, amber flag (2 points) for potential clinically significant DDIs manageable by dose adjustment or clinical monitoring, yellow flag (1 point) for DDIs of weak clinical relevance with no need of a priori dosage adjustment or monitoring, and a green flag (0 points) for no interactions. Amber flag DDIs will be downgraded to 1 point if there is evidence that the DDI was managed correctly (i.e. DTG administered 2 hours before or 6 hours after taking divalent cations). The sum of all points at visit 6, week 48 will be compared to baseline.
Proportion of individuals reporting depression assessed by Patient Health Questionnaire-9 Week 0 and 48 Depression will be assessed at baseline and week 48, assessed using the Patient Health Questionnaire-9 (PHQ-9)
Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI Week 0 to 48 Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI at any study visit between baseline and week 48, based on the results from the Liverpool drug interaction database (www.hiv-druginteractions.org).
Patient report outcomes concerning differences in treatment satisfaction between both groups assessed by HIV Treatment Satisfaction Questionnaires Week 48 The investigators will assess the differences in treatment satisfaction between both groups at week 48, as determined using the validated HIV Treatment Satisfaction Questionnaires HIVTSQ.
Proportion of individuals who develop a detectable HBV viral load Weeks 24 and 48 Proportion of individuals with a positive anti-HBc and negative anti-HBs ("anti-HBc alone") who develop a detectable HBV viral load (\>50 IU/mL) at weeks 24 and 48.
Cumulative cost of all ART drugs used Week 0 to 48 The 48-weeks cumulative cost of the received ART regimen will be calculated using prices published by the Federal Office of Public Health (https://www.spezialitaetenliste.ch/ShowPreparations.aspx).
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 Needs regarding the booster-free regimen or regarding ART in general for participants included in the observational cohort.
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 Expectations regarding the booster-free regimen or regarding ART in general for participants included in the observational cohort.
Proportion of patients with DDI leading to suboptimal management of comorbidities Week 0 and 48 Proportion of patients with DDI leading to suboptimal management of comorbidities between baseline and week 48, as reported by the cohort physician.
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 Perception of the trial and/or of HIV-related research in general.
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 Perspectives on how the participants' current and anticipated needs can be addressed by research.
Acceptability conditions of participation in the trial assessed by qualitative interviews in a subset of approximately 30 trial participants Week 0 and 48 Acceptability conditions, understood as all barriers and facilitators to be involved in a trial.
Trial Locations
- Locations (8)
Inselgruppe AG
🇨🇭Bern, Switzerland
University Hospital Geneva
🇨🇭Geneva, Switzerland
University of Lausanne Hospitals
🇨🇭Lausanne, Switzerland
Lugano Regional Hospital Lugano
🇨🇭Lugano, Switzerland
Cantonal Hospital Aarau
🇨🇭Aarau, Aargau, Switzerland
University Hospital Basel
🇨🇭Basel, Switzerland
Cantonal Hospital of St. Gallen
🇨🇭St. Gallen, Switzerland
University Hospital Zürich
🇨🇭Zürich, Switzerland