HIV
Conditions
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.
Interventions
DRUGBiktarvy
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
Sponsors
Tufts Medical Center
Boston Medical Center
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global CFR | baseline and week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Stress Global MBF | baseline and 24 weeks | 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. |
| Change in Serum Biomarkers of Inflammation (Hs-CRP (in mg/L)) | Baseline and 24 weeks | 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. |
| Change in Myocyte Injury and Strain (hs Troponin (in ng/L)) | Baseline and 24 weeks | 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. |
| Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL)) | Baseline and 24 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | HIV Patients on Stable Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 56.44 years STANDARD_DEVIATION 6.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 2 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
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.
Time frame: baseline and week 24
Population: We enrolled men 45 years and over and women 55 years and over with HIV who were stable on a DTG/3TC/ABC regimen with virologic suppression for at least one year, and with at least one coronary risk factor (current smoking, dyslipidemia, hypertension, diabetes, obesity, or a calculated 10-year predicted risk of cardiovascular events of 7.5 percent or over) but without overt cardiovascular disease.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HIV Patients on Stable Therapy | Change in Global CFR | -.05 ratio |
Secondary
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.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HIV Patients on Stable Therapy | Change in Myocyte Injury and Strain (hs Troponin (in ng/L)) | -0.04 ng/L |
Secondary
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.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HIV Patients on Stable Therapy | Change in Myocyte Injury and Strain (NT-proBNP (in pg/mL)) | -14.2 pg/mL |
Secondary
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.
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HIV Patients on Stable Therapy | Change in Peak Stress Global MBF | 0.09 mL/min/g |
Secondary
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.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HIV Patients on Stable Therapy | Change in Serum Biomarkers of Inflammation (Hs-CRP (in mg/L)) | -0.40 mg/L |