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

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

Detailed Description
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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.

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

Conditions
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Hiv

Intervention / Treatment
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* Drug: Dolutegravir / Lamivudine Pill


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DTG/3TC<br>HIVRNA suppressed HIV patients who switched to DTG/3TC | Drug: Dolutegravir / Lamivudine Pill<br>* 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<br>|
| Triple drug cART<br>Matched HIVRNA suppressed patients who remained on triple drug cART | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy 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 OT population | 1 year | 
| Efficacy 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 ITT 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 |