Effects of Biktarvy on CFR in Stable HIV Patients

NCT ID: NCT03656783

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-14
• Study Completion Date: 2021-09-15

Brief Summary

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.

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.

Conditions

HIV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: OTHER

Biktarvy

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Marcelo F. Di Carli, MD, FACC

Chief of Nuclear Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marcelo Di Carli, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Huck DM, Weber B, Parks S, Divakaran S, Brown JM, Bibbo CF, Barrett L, Hainer J, Bay C, Martell L, Kogelman L, Triant VA, Chu J, Lin NH, Melbourne K, Sax PE, Di Carli MF. Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy. J Am Heart Assoc. 2023 Nov 21;12(22):e029541. doi: 10.1161/JAHA.123.029541. Epub 2023 Nov 10.

Reference Type: DERIVED

PMID: 37947105 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2018P001579

Identifier Type: -

Identifier Source: org_study_id