Effects of Biktarvy on CFR in Stable HIV Patients (BETTER)

Effects of Biectegravir-Emtricitabine-Tenofovir Alafenamide on Coronary Flow Reserve in Stable HIV Patients (B/F/TAF-CFR) - Pilot Study

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single pill regimen that was approved by the FDA in February 2018 for treatment of HIV. The marketed name of the drug is Biktarvy. In two phase 3 comparative clinical trials, including one with ABC/3TC/DTG, it was found to be non-inferior to dolutegravir-containing regimens in terms of virologic outcomes. B/F/TAF was also well tolerated, with few discontinuations for adverse events. As a result, B/F/TAF is an ideal non-abacavir containing regimen to assess the effect of removing ABC on coronary flow reserve.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Biktarvy

Detailed Description

Positron emission tomography (PET) imaging allows precise and reproducible quantification of myocardial blood flow, thereby providing a direct assessment of coronary vascular health. Coronary flow reserve (CFR, calculated as the ratio of peak hyperemic myocardial blood flow over that at rest) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, vessel remodeling, and microvascular dysfunction resulting from endothelial cell dysfunction on myocardial tissue perfusion across the entire coronary circulation. These processes have direct relevance to the underlying vascular pathobiology in patients with HIV infection. Consequently, quantitative CFR provides a unique opportunity to examine the potential impact of novel therapies on the biology of the disease and its association with cardiovascular outcomes. By testing the fundamental concept of whether novel ART therapies in HIV can lead to improved coronary blood flow and myocardial tissue perfusion, TAF-CFR would provide important mechanistic insights of the capabilities of TAF therapy to improve key determinants of clinical risk.

This is an open label, multicenter, uncontrolled, single arm pilot study. Patients with stable HIV currently treated with abacavir/lamivudine/dolutegravir STR regimens will be eligible for the B/F/TAF-CFR study. PET scans will be performed after enrollment while on the abacavir/lamivudine/dolutegravir STR regimen and at 24 weeks after the switch to B/F/TAF regimen. Patients will be encouraged to remain on stable medical therapy throughout the enrollment period.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with HIV on abacavir/lamivudine/dolutegravir STR regimens for at least 1 year fulfilling the following inclusion criteria:

1. age ≥ 45 years for men and ≥ 55 years for women;
2. at least one coronary risk factor including smoking, dyslipidemia, hypertension, obesity (BMI >30) or diabetes, or a calculated 10-year risk of heart attack of 7.5% or higher;
3. HIV RNA < 200 copies/mL at last clinical measurement, done within the past 12 months prior to screening, with no intervening HIV RNA > 200;
4. Screening HIV RNA < 50 copies/mL, CBC, and chemistries that, in the judgment of the investigator, do not preclude the use of Biktarvy.

Exclusion Criteria:

1. patients not fulfilling inclusion criteria;
2. unstable HIV disease or other medical condition that, in the opinion of the investigator, would interfere with the conduct of the study;
3. history of cardiomyopathy (LVEF <40%) or significant valvular heart disease;
4. cirrhosis;
5. end stage renal disease on dialysis;
6. uncontrolled hypertension (defined as SBP >200 or DBP >110);
7. pregnancy;
8. Patients requiring medications contraindicated with the components of B/F/TAF;
9. Patients on active treatment for severe asthma or severe COPD.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: HIV patients on stable therapy; HIV patients on stable therapy switching from Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF)

Drug: Biktarvy; Open-label, multicenter, single-arm study to Evaluate the Safety and Efficacy of Switching from Regimens Consisting of Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV-Infected Adult Subjects; Other Names: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global CFR	Change in global coronary flow reserve, as measured by PET imaging at baseline and 24 weeks after initiation of B/F/TAF therapy. Coronary flow reserve (CFR), the ratio of peak vasodilator stress to rest myocardial blood flow (MBF), represents the maximal ability to augment coronary flow and myocardial perfusion. Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired MBFR is defined as a ratio of <2.0, which is associated with increased cardiovascular risk.	baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Stress Global MBF	Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after initiation of B/F/TAF. Absolute MBF was computed from the rest and stress myocardial perfusion PET images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and a two-compartment tracer kinetic model. Impaired stress MBF is defined as <1.8 mL/min/g and is associated with increased cardiovascular risk.	baseline and 24 weeks
Change in Serum Biomarkers of Inflammation (Hs-CRP (in mg/L))	Change in serum biomarkers of inflammation (hs-CRP (in mg/L)) at 24 weeks after initiation of B/F/TAF. Serum biomarkers of inflammation (high sensitivity C-reactive protein) were measured. hs-CRP > 1 mg/L are considered abnormal and associated with increased cardiovascular risk.	Baseline and 24 weeks
Change in Myocyte Injury and Strain (hs Troponin (in ng/L))	Change in Myocyte Injury and Strain (hs Troponin (in ng/L)) at 24 weeks after initiation of B/F/TAF. Serum biomarkers of myocardial injury/strain (high sensitivity troponin) were measured. hs-troponin >14 ng/L are considered abnormal and associated with increased cardiovascular risk.	Baseline and 24 weeks
Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL))	Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL)) at 24 weeks after initiation of B/F/TAF. Serum biomarkers of myocardial injury/strain (NT-pro-BNP) were measured. NT-proBNP > 100 pg/mL are considered abnormal and associated with increased cardiovascular risk.	Baseline and 24 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Boston Medical Center; Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 14, 2018
• Primary Completion (ACTUAL): September 15, 2021
• Study Completion (ACTUAL): September 15, 2021

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (ACTUAL): September 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide
• Other Study ID Numbers: 2018P001579

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