Switch From Dual Regimens Based on Dolutegravir Plus a Reverse Transcriptase Inhibitor to E/C/F/TAF in Virologically Suppressed, HIV-1 Infected Patients (Be-OnE)

Study Overview
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Brief Summary
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Research hypothesis: Switching from dual regimens based on dolutegravir plus a RTI to a single tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), lowers the exposure to Residual Viremia (and hence the risk of viral rebound), without increasing treatment toxicity.

Detailed Description
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Study design Randomized, single-center, open-label, 96-week superiority study. Patients with HIV-RNA <50 copies/mL while receiving DTG plus one RTI will be randomized 1:1 to continue the ongoing treatment or to switch to E/C/F/TAF. Randomization list will be a computer-generated list (with equal block sizes) and will be incorporated within an electronic clinical report form (eCRF). Patients will be evaluated at screening, baseline, week 4, 8, 16, 24, 32, 40, 48, 60, 72, 84, 96 or premature discontinuation. At each visit the following evaluations will be performed: clinical assessment. routine laboratory tests (hematological tests and clinical chemistry). Additional blood samples will be collected at specified visits for storage and further determinations (e.g. RV by a single-copy assay). During follow-up, at different timepoints, patients will additionally undergo HIV-DNA quantification in PBMCs (BL, 48 and 96 weeks) and quality of life (QOL) and adherence assessement (BL, 48 and 96 weeks). Viral load will be assessed by Abbott Real time PCR (Abbott RealTime HIV-1) Residual viremia (RV) will be defined as any detectable HIV-RNA value below 50 copies/mL Virologic failure will be defined as a confirmed rebound in plasma HIV-RNA levels ≥ 50 copies/mL Subjects who meet a protocol-defined virologic failure during follow-up will be discontinued from the study. At virologic failure subjects will perform genotypic HIV resistance testing and a determination in plasma of elvitegravir or DTG Cthrough. HIV-DNA will be extracted from 1x106 peripheral blood mononuclear cells (PBMCs) by using Qiagen DNA extraction kit and quantified by Real Time PCR (ABI Prism 7900).

Official Title
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Open Label, Randomized (1:1) Clinical Trial to Evaluate Switching From Dual Regimens Based on Dolutegravir Plus a Reverse Transcriptase Inhibitor to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed, HIV-1 Infected Patients (Be-OnE Study).

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet
* Drug: Dolutegravir 50 mg plus one RTI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Willing and able to provide informed consent On a stable (at least 3 months) antiretroviral therapy with DTG 50 mg QD plus one RTI HIV-RNA <50 copies/mL since at least 6 months Exclusion Criteria: Active AIDS-defining condition (except Kaposi's sarcoma non requiring systemic chemotherapy) Serious illness requiring systemic treatment and/or hospitalization Current use of immunomodulant or immunosuppressive drugs Need (or will likely need) of treatment with antacids Use of drugs contraindicated with study drugs, according to technical sheets Previous suboptimal therapies with NRTIs or presence of TAMs (type 1 or 2) in previous resistance tests (patients with the 184I/V mutation alone are allowed to enter the study) Resistance or previous virological failure to InSTIs Detectable HCV-RNA Documented allergy to COBI or EVG or FTC or tenofovir. Absolute neutrophil count (ANC) <500/µL Haemoglobin <8.0 g/dL Platelet count <50,000/µL eGFR <30 mL/min/1.73m2 by CKD-EPI equation Alanine aminotransferase (ALT) more than 5 times the upper limit of normal (ULN) Presence of Child Pugh Class B or C liver cirrhosis. Pregnancy or breastfeeding Woman of childbearing potential who does not agree to adopt highly effective contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatments Genvoya 150Mg-150Mg-200Mg-10Mg Tablet ( 1 pill every 24 hours) Dolutegravir 50 mg (1 pill every 24 hours) plus one Reverse Trascriptase Inhibitor (at label dose)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genvoya 150Mg-150Mg-200Mg-10Mg Table<br>switch to the treatment Genvoya 150Mg-150Mg-200Mg-10Mg Table (1 pill every 24 hour) | Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet<br>* switch to Genvoya 150Mg-150Mg-200Mg-10Mg Tablet in patients virologically suppressed HIV-1 infected patients.<br>|
| Active Comparator: Dolutegravir 50 mg plus one RTI (at label dose)<br>Continuing Dolutegravir 50 mg (1 pill every 24 hours) plus one RTI (at label dose) | Drug: Dolutegravir 50 mg plus one RTI<br>* Continuing Dolutegravir 50 mg (1 pill every 24 hours) plus one RTI (at label dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual Viremia | To investigate RV through 48 weeks in virologically suppressed patients randomized to continue treatment with DTG plus a single RTI or to switch to E/C/F/TAF. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| virological rebound | To investigate the occurrence of virological rebound above 50 HIV-RNA copies/mL; | 48 weeks | 
| viral reservoir | To investigate changes in viral reservoir (HIV-DNA) | 48 weeks | 
| QOL | To investigate changes in the quality of life (administration of questionnaire ISSQoL uses five- point Likert scales 1 never 2 rarely 3 sometimes 4 often 5 always) | 48 weeks | 
| Adherence | To investigate changes in adherence (administration of questionnaire uses scale ranges from 0 to 100) | 48 weeks | 
| Virological failure | proportion of patient in virological rebound | 96 weeks | 
| viral reservoir | change in viral reservoir (HIV-DNA extracted from peripheral blood mononuclear cells by using Qiagen DNA extraction kit and quantified by Real Time PCR) | 96 weeks | 
| QOL | To investigate changes in the quality of life (administration of questionnaire To investigate changes in the quality of life (administration of questionnaire ISSQoL uses five- point Likert scales 1 never 2 rarely 3 sometimes 4 often 5 always)) | 96 weeks | 
| Adherence. | To investigate changes in adherence (administration of questionnaire uses scale ranges from 0 to 100 ) | 96 weeks |