Effects of Biktarvy on CFR in Stable HIV Patients

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.

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.