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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Biktarvy 50 mg/200 mg/25 mg film-coated tablets

Detailed Description

The Primary objectives are:

1. To assess viral efficacy of the reductions of BETAF regimen dose at 12 weeks (on-treatment and intent-to-treat populations).
2. To asess viral efficacy of the reduction of BETAF regimen dose at 48 weeks (on-treatment and intent-to-treat populations).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial Barcelona

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): June 5, 2024

Study Registration Dates

• First Submitted: October 19, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections
• Other Study ID Numbers: BETAF-RED

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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