Safety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults

Study Overview
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Brief Summary
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This is a phase IV, unicentric, open, pilot, randomized, controlled trial to evaluate Bictegravir/FTC/TAF. The study will be developed at a single clinical care centre:Hospital Clínic de Barcelona, Barcelona, Spain. The aim of this study is to assess the feasibility of dose redutions of Bictegravir/FTC/TAF in virologically suppressed HIV-infected adults on BETAF once daily. The reduction of drug exposure will have a significant positive impact on parameters reflecting potential toxicities associated with bictegravir or tenofovir.

Detailed Description
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The Primary objectives are: To assess viral efficacy of the reductions of BETAF regimen dose at 12 weeks (on-treatment and intent-to-treat populations). To asess viral efficacy of the reduction of BETAF regimen dose at 48 weeks (on-treatment and intent-to-treat populations).

Official Title
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Safety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable and asymptomatic HIV-infected adults (≥18 years) on BETAF once daily for at least the previous 6 months. Plasma HIV-1 RNA less than 50 copies/mL for at least the previous 6 months. CD4 cell counts greater than 350 cells/mL at the time of consideration for the study. Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods. Patients agreed to participate. Exclusion Criteria: Prior virological failure to any antiretroviral regimen or documented. Any diagnosis of psychiatric illness. Alcohol abuse or illicit drug consumption (based on their past medical history and specific questions at the time of recruitment). Patients co-infected with HIV and active hepatitis B or C virus. Any other condition at the doctor's discretion that did not allow ensuring a correct adherence.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BETAF OD arm<br>one tablet taken orally once daily | Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets<br>* The duration of the study treatment will be 48 weeks.<br>|
| Experimental: BETAF 3W arm<br>one tablet taken orally 3 days per week : Mondays, Wednesdays, and Fridays | Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets<br>* The duration of the study treatment will be 48 weeks.<br>|
| Experimental: BETAF 2W arm<br>one tablet taken orally 2 days per week : Mondays, and Thursdays | Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets<br>* The duration of the study treatment will be 48 weeks.<br>|
| Experimental: BETAF 1W arm<br>one tablet taken orally 1 days per week : Mondays | Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets<br>* The duration of the study treatment will be 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral efficacy of the reduction of BETAF regimen dose per week at 12 weeks. | standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL | at 12 weeks | 
| Viral efficacy of the reduction of BETAF regimen dose per week at 48 weeks. | standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL | at 48 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological efficacy assessed by Standard plasma viral load | -Standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL) | at 4, 24, and 36 weeks. | 
| Virological efficacy assessed by Blips (VL ≥50 copies/mL followed) | -Blips (VL ≥50 copies/mL followed) | at 0, 4, 12, 24, 36, and 48 weeks | 
| Virological efficacy assessed by Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL) | -Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL) | at 0, 4, 12, 24, 36, and 48 weeks | 
| Virological efficacy assessed by Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL) | -Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL) | at 0, 12, and 48 weeks. | 
| Virological efficacy assessed by HIV-1 reservoir (total and integrated DNA (copies/106 PBMC)) in CD4 cells | - HIV-1 reservoir (total and integrated DNA) in CD4 cells | at 0, 12, and 48 weeks. | 
| Virological efficacy assessed by ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance | In case of virological failure, ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance | at 0, 4, 12, 24, 36 and 48 weeks | 
| Immunological safety assessed by CD4 and CD8 cells | -CD4 and CD8 (cells/mL) will be combined to report CD4/CD8 ratio. | at 0, 12 and 48 weeks | 
| Immunological safety 2 assessed by hsCRP, IL-6 and adiponectin levels | -Inflammation (hsCRP, IL-6, adiponectin) (µg/mL), IL-6 (pg/mL), adiponectin (µg/mL) levels | at 0, 12 and 48 weeks | 
| Immunological safety assessed by sCD14 and CD163 as a Immune activation markers | - sCD14(ng/l ) and CD163 (ng/l) plasma levels | at 0, 12 and 48 weeks | 
| Subclinical toxicity assessed by BMI index | - Weight and body mass index (BMI)(kg/m2) changes | at 4, 12, 24, 36, and 48 | 
| Body composition assessed by DEXA scan | -Body composition (g/cm) (fat, fat-free mass, and bone by DEXA) | at 0 and 48 weeks | 
| Impact on sleep quality assessed by Pittsburg Sleep Quality | - Impact on sleep quality will be evaluated througth Pittsburg Sleep Quality (visual analog score)questionaire at 0 and 48 weeks | at 0 and 48 weeks | 
| Quality of life questionnaire assessed by EuroQol Group EQ-5D™ questionnaire | - Impact on quality of life will be evaluated througth EuroQol Group EQ-5D™ (Units on a Scale) | at 0 and 4,12,24,36, 48 weeks | 
| Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) assessed by Plasma levels of bictegravir, emtricitabine and tenofovir | - Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L) | at 0, 12, and 48 weeks | 
| Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim) | Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L) | at 0, 12, and 48 weeks |