Defining the Potency of DTG/3TC for Suppressed HIV Patients in Real-life: the DUALING Study (DUALING)

Defining the Potency of DTG/3TC for Suppressed HIV Patients in Real-life: the DUALING Study.

This study aims to determine real-life clinical efficacy of virally suppressed patienst switching to DTG/3TC compared to DTG triple drug cART controls

Study Overview

• Status: Active, not recruiting
• Conditions: Hiv
• Intervention / Treatment: Drug: Dolutegravir / Lamivudine Pill

Detailed Description

Dolutegravir (DTG) based dual antiretroviral therapy constitutes a paradigm shift from triple drug based therapy. Data outside clinical trials are scarce. This study evaluates the value of DTG/3TC in real life.

• Study Type: Observational
• Enrollment (Actual): 2040

Contacts and Locations

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Goes, Netherlands
    • Admiraal De Ruyter Ziekenhuis
  • Haarlem, Netherlands
    • Spaarne Gasthuis
  • Rotterdam, Netherlands
    • Maasstad Hospital
  • Rotterdam, Netherlands, 3015 CN
    • Erasmus MC
  • Rotterdam, Netherlands, 3015 CN
    • MC Haaglanden
  • Tilburg, Netherlands
    • Elisabeth Tweesteden Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

To be eligible as case in the study, plasma HIVRNA must be <50c/mL on triple drug cART containing 2NRTI at switch to DTG/3TC and no key mutations associated with major 3TC (i.e. M184V/I only) or DTG resistance of at least low level according to the Stanford HIV drug resistance database should be present. Patients with no genotyping results available at baseline will be eligible for inclusion in this study. Cases should not have documented inadherence in the preceding 3 months or HepB coinfections. These data on adherence and HepB is routinely collected at switching to DTG/3TC. Controls are matched on predefined criteria.

Description

Inclusion Criteria:

Plasma HIVRNA <50c/mL on triple drug cART regimen including 2NRTI In care in a HIV treatment center in the Netherlands Consented to ATHENA participation

Exclusion Criteria:

Documented mutations associated with 3TC or DTG resistance of at least low level Documented inadherence by the treating physician or HepB coinfection (cases only)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DTG based switchers to DTG/3TC; HIVRNA suppressed HIV patients who switched to DTG/3TC
DTG based triple drug cART; Matched HIVRNA suppressed patients who remained on triple drug DTG based cART
non-DTG based switchers to DTG/3TC	Drug: Dolutegravir / Lamivudine Pill; HIVRNA suppressed patients without documented M184V mutation in HIV RT and who are hepatitis B immune or have no risk factors for acquiring hepatitis B
non-DTG based triple drug cART; Matched HIVRNA suppressed patients who remained on triple drug non-DTG based cART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy On Treatment (OT)	Proportion of subjects with treatment failure in the DTG/3TC versus 3-drug DTG containing cART group up to 1 year of follow up in the on treatment population	1 year
Efficacy Intention to Treat (ITT)	Proportion of subjects with treatment failure in the DTG/3TC versus 3-drug DTG containing cART group up to 1 year of follow up in the intention to treat population.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term efficacy	Proportion of subjects with treatment failure in the DTG/3TC versus 3-drug DTG containing cART group after 2 and 5 year of follow up in the OT and ITT population.	5 year
Long term efficacy subgroups	Proportion of subjects with treatment failure in the DTG/3TC versus 3-drug cART overall, and according to INSTI/PI/NNRTI (non-DTG) subgroups, after 1, 2 and 5 year of follow up in the OT and ITT population.	5 years
Time to event analysis	Time to treatment failure in the DTG/3TC versus 3-drug DTG containing cART group and 3drug cART overall (including according to INSTI/PI/NNRTI (non-DTG) subgroups) according to the ITT and the OT population during 1, 2 and 5 years of follow up.	5 years
Plasma viral load	Proportion of plasma viral load measurements above the limit of detection of the PCR but <50 (between 20 and 50 c/mL), proportion of viral blips of HIVRNA >50 once with plasma HIVRNA measured <=50 c/mL before and after, proportion of plasma HIVRNA >200 and >1000c/mL on DTG/3TC versus 3-drug DTG containing cART group and 3drug cART overall and according to INSTI/PI/NNRTI (non-DTG) subgroups.	5 years
Drug associated resistance	Proportion of patients with emergent mutations associated with resistance to DTG, 3TC or the third antiviral agent in cases versus controls.	5 years
Treatment failure predictors	Predictor variables for treatment failure in the DTG/3TC, 3-drug (non) DTG containing cART group and 3drug cART overall at the 1, 2, and 5 years of follow up in the OT and ITT population according to 1) sex, 2) ethnicity (Caucasian, African, other), 3) CD4+Tcell nadir, 4) HIVRNA zenith, duration of suppressive cART (</>1year and </>5 year), 5) presence of mutations, 6) CD4/CD8 ratio nadir 7) documented history in ATHENA database of virological failure (without selection of M184VI or major DTG related RAMs) or inadherence.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interim analysis	Analysis of endpoints at 3 and 4 years of follow up	3 and 4 years
Side effects	Proportion of subjects with switches due to side effects in the DTG/3TC versus 3-drug (non) DTG containing cART group and 3drug cART overall after 1, 2, 3, 4 and 5 years of follow up	5 years
Cost-effectiveness	Cost-effectiveness analysis of the switch from triple cART to DTG/3TC.	5 years

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Catharina Ziekenhuis Eindhoven; Elisabeth-TweeSteden Ziekenhuis; Rijnstate Hospital; Maasstad Hospital; Spaarne Gasthuis; Medisch Spectrum Twente; Admiraal de Ruyter Hospital; Haaglanden Medical Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): November 1, 2023
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir; Lamivudine
• Other Study ID Numbers: DUALING

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Other research groups can contact the PI with a research question to obtain IPD.
• IPD Sharing Time Frame: Up to 15 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No