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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

Phase 4
Completed
Conditions
HIV Infections
Interventions
Registration Number
NCT05602506
Lead Sponsor
Fundacion Clinic per a la Recerca Biomédica
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BETAF OD armBiktarvy 50 mg/200 mg/25 mg film-coated tabletsone tablet taken orally once daily
BETAF 2W armBiktarvy 50 mg/200 mg/25 mg film-coated tabletsone tablet taken orally 2 days per week : Mondays, and Thursdays
BETAF 1W armBiktarvy 50 mg/200 mg/25 mg film-coated tabletsone tablet taken orally 1 days per week : Mondays
BETAF 3W armBiktarvy 50 mg/200 mg/25 mg film-coated tabletsone tablet taken orally 3 days per week : Mondays, Wednesdays, and Fridays
Primary Outcome Measures
NameTimeMethod
Viral efficacy of the reduction of BETAF regimen dose per week at 12 weeks.at 12 weeks

standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL

Viral efficacy of the reduction of BETAF regimen dose per week at 48 weeks.at 48 weeks.

standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL

Secondary Outcome Measures
NameTimeMethod
Immunological safety assessed by CD4 and CD8 cellsat 0, 12 and 48 weeks

-CD4 and CD8 (cells/mL) will be combined to report CD4/CD8 ratio.

Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) assessed by Plasma levels of bictegravir, emtricitabine and tenofovirat 0, 12, and 48 weeks

- Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)

Virological efficacy assessed by Standard plasma viral loadat 4, 24, and 36 weeks.

-Standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL)

Virological efficacy assessed by Blips (VL ≥50 copies/mL followed)at 0, 4, 12, 24, 36, and 48 weeks

-Blips (VL ≥50 copies/mL followed)

Virological efficacy assessed by HIV-1 reservoir (total and integrated DNA (copies/106 PBMC)) in CD4 cellsat 0, 12, and 48 weeks.

- HIV-1 reservoir (total and integrated DNA) in CD4 cells

Immunological safety 2 assessed by hsCRP, IL-6 and adiponectin levelsat 0, 12 and 48 weeks

-Inflammation (hsCRP, IL-6, adiponectin) (µg/mL), IL-6 (pg/mL), adiponectin (µg/mL) levels

Quality of life questionnaire assessed by EuroQol Group EQ-5D™ questionnaireat 0 and 4,12,24,36, 48 weeks

- Impact on quality of life will be evaluated througth EuroQol Group EQ-5D™ (Units on a Scale)

Virological efficacy assessed by Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)at 0, 4, 12, 24, 36, and 48 weeks

-Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)

Impact on sleep quality assessed by Pittsburg Sleep Qualityat 0 and 48 weeks

- Impact on sleep quality will be evaluated througth Pittsburg Sleep Quality (visual analog score)questionaire at 0 and 48 weeks

Virological efficacy assessed by Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)at 0, 12, and 48 weeks.

-Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)

Virological efficacy assessed by ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistanceat 0, 4, 12, 24, 36 and 48 weeks

In case of virological failure, ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance

Immunological safety assessed by sCD14 and CD163 as a Immune activation markersat 0, 12 and 48 weeks

- sCD14(ng/l ) and CD163 (ng/l) plasma levels

Subclinical toxicity assessed by BMI indexat 4, 12, 24, 36, and 48

- Weight and body mass index (BMI)(kg/m2) changes

Body composition assessed by DEXA scanat 0 and 48 weeks

-Body composition (g/cm) (fat, fat-free mass, and bone by DEXA)

Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim)at 0, 12, and 48 weeks

Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)

Trial Locations

Locations (1)

Hospital Clinic i Provincial Barcelona

🇪🇸

Barcelona, Spain

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