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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
210
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.
Cantonal Hospital Aarau
Aarau, Canton of Aargau, Switzerland
University Hospital Basel
Basel, Switzerland
Inselgruppe AG
Bern, Switzerland
University Hospital Geneva
Geneva, Switzerland
University of Lausanne Hospitals
Lausanne, Switzerland
Lugano Regional Hospital Lugano
Lugano, Switzerland
Cantonal Hospital of St. Gallen
Sankt Gallen, Switzerland
University Hospital Zürich
Zurich, Switzerland
Loss of viral suppression
Difference in the proportion of individuals with an HIV-RNA ≥50 cp/mL at 48 weeks between the treatment arms.
Time frame: Week 48
Changes in DDI score from week 0 to 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.
Time frame: Week 0 and 48
Patient report outcomes concerning changes in treatment satisfaction between baseline and 48 weeks, as determined using the HIV Treatment Satisfaction Questionnaire HIVTSQc (change version).
The investigators will assess changes in treatment satisfaction between week 0 and 48 using the validated HIV Treatment Satisfaction Questionnaire HIVTSQc (change version).
Time frame: Week 0 to 48
Proportion of patients experiencing confirmed virological failure
Proportion of patients experiencing confirmed virological failure, defined as 2 consecutive plasma HIV viral loads ≥200 copies/mL
Time frame: Week 48
Proportion of individuals detected with new drug resistance
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).
Time frame: Week 0 to 48
Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI
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).
Time frame: Week 0 to 48
Proportion of patients with DDI leading to suboptimal management of comorbidities
Proportion of patients with DDI leading to suboptimal management of comorbidities between baseline and week 48, as reported by the cohort physician.
Time frame: Week 0 and 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
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
Time frame: Week 48
Patient report outcomes concerning differences in treatment satisfaction between both groups assessed by HIV Treatment Satisfaction Questionnaires
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.
Time frame: Week 48
Proportion of individuals reporting depression assessed by Patient Health Questionnaire-9
Depression will be assessed at baseline and week 48, assessed using the Patient Health Questionnaire-9 (PHQ-9)
Time frame: Week 0 and 48
Changes in intact proviral HIV-DNA levels
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.
Time frame: Week 0 to 48
Proportion of individuals who develop a detectable HBV viral load
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.
Time frame: Weeks 24 and 48
Cumulative cost of all ART drugs used
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).
Time frame: Week 0 to 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
Perception of the trial and/or of HIV-related research in general.
Time frame: Week 0 and 48
Acceptability conditions of participation in the trial assessed by qualitative interviews in a subset of approximately 30 trial participants
Acceptability conditions, understood as all barriers and facilitators to be involved in a trial.
Time frame: Week 0 and 48
Needs regarding the booster-free regimen or regarding ART in general assessed by qualitative interviews in a subset of approximately 30 trial participants
Needs regarding the booster-free regimen or regarding ART in general for participants included in the observational cohort.
Time frame: 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
Expectations regarding the booster-free regimen or regarding ART in general for participants included in the observational cohort.
Time frame: 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
Perspectives on how the participants' current and anticipated needs can be addressed by research.
Time frame: Week 0 and 48
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