Clinical trial NCT03656783
Conditions: HIV
Sponsor: Brigham and Women's Hospital
Start date: 2018-09-14; Completion date: 2021-09-15
Enrollment: 25 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: HIV patients on stable therapy switching from Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) to the Bictegravir/ Emtricitabine/Tenofovir Alafenamide (B/F/TAF)
Interventions: intervention 1: Biktarvy
Intervention descriptions: intervention 1: 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

Protocol documents:
Prot_SAP_000.pdf: 
 
1
DETAILED PROTOCOL 
 
 
EFFECTS OF BICTEGRAVIR-EMTRICITABINE-TENOFOVIR ALAFENAMIDE ON CORONARY FLOW 
RESERVE IN STABLE HIV PATIENTS (B/F/TAF-CFR) – PILOT STUDY 
 
 
 
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 
 
Investigators: 
Marcelo F. Di Carli, MD, Paul E. Sax, MD, Nina Lin, MD, Laura Kogelman, MD 
 
 
Institution: 
Brigham and Women’s Hospital, Boston, MA 
Boston Medical Center, Boston, MA 
Tufts Medical Center, Boston, MA 
Massachusetts General Hospital, Boston, MA 
 
18 JUNE 2018 
07 August 2018 
20 December 2018 
January 4, 2019 
February 5, 2019 
March 22, 2019 
April 15, 2019 
April 30, 2019 
September 12, 2019 
 
 
 
 
 
 
 


 
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1.  
BACKGROUND AND SIGNIFICANCE  
The endothelium provides a permeability barrier for the vasculature, maintains a nonthrombogenic 
surface, regulates vascular tone and tissue flow, and inhibits vascular smooth muscle cell growth. In the 
presence of inflammatory cytokines, endothelial cells are activated which facilitates leukocyte adhesion 
and migration into the vessel wall, production of prothrombotic substances, and vasoconstriction, 
thereby creating a proatherogenic and procoagulant environment. Consequently, inflammation is a key 
mediator of a constellation of abnormalities that initiate and accelerate the progression of 
atherosclerosis. 
HIV-specific immune dysregulation promotes endothelial and immune cell activation. Indeed, 
antiretroviral (ART)-naive HIV positive patients have higher levels of endothelial immune activation 
markers (e.g., IL-6, VICAM-1 and others) than non-HIV controls. ART-naïve HIV positive patients also 
show evidence of endothelial-cell dysfunction, as assessed by brachial artery reactivity. Treatment with 
ART has been shown to reduce biomarker evidence of endothelial cell activation in observational and 
randomized trials, and some of these drugs also appear to improve endothelial function. However, most 
prior evidence of the direct biologic effect of HIV viral infection and its changes with therapy on 
coronary vascular function has been indirect through the measurement of circulating biomarkers or 
brachial artery reactivity. 
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.  
 
JUSTIFICATION FOR THE USE OF CFR AS A SURROGATE MARKER OF CLINICAL RISK 
Noninvasive quantification of coronary flow reserve improves diagnosis and risk assessment in non-
HIV patients with CAD. Noninvasive quantification of coronary blood flow and flow reserve has been the 
research focus of our group for over 20 years. Our group has developed and validated methodology for 
flow quantification and disseminated this technology for broad access and use. We and others have 
demonstrated that CFR is a quantitative unique phenotyping tool to assess vascular health and pre-
clinical atherosclerosis which, in higher risk patients, can reveal flow-limiting coronary artery stenosis, 
thereby improving the accuracy of myocardial perfusion imaging in the diagnostic evaluation of known 
or suspected CAD 1-4. More recent data support the notion that coronary vascular dysfunction, as 
quantified by reduced CFR, is highly prevalent among patients with known or suspected CAD2, 5, 
increases the severity of inducible myocardial ischemia (beyond the effects of upstream coronary 
obstruction)6 and sub-clinical myocardial injury7, and identifies patients at high risk for serious cardiac 
adverse events, including cardiac death8-11. Thus, CFR is a robust measure of the integrated 
hemodynamic effects of epicardial CAD, diffuse atherosclerosis, vessel remodeling, and microvascular 
dysfunction on myocardial perfusion. In the presence of increased oxygen demand, a decreased CFR 


 
3
reflects an imbalanced supply-demand relationship that may lead to myocardial ischemia, subclinical LV 
systolic and diastolic dysfunction, clinical symptoms and, ultimately, death. There is also emerging 
evidence that a reduced global CFR may help identify patients who benefit most from 
revascularization12.  
Systemic inflammation is associated with coronary vascular dysfunction. There is increasing evidence 
that coronary vascular dysfunction is associated with systemic inflammation and may precede or coexist 
with high-risk coronary atherosclerosis. Compared to healthy subjects, patients with rheumatoid 
arthritis or systemic lupus erythematosus, without significant CAD on invasive angiography, have 
impaired CFR to a degree directly related to disease duration13. In patients with cardiac syndrome X 
(CSX) with exertional angina and ST-segment depression on exercise stress testing but normal luminal 
coronary angiography, only those with elevated high sensitivity C-reactive protein (hsCRP, >3 mg/L) have 
reduced CFR14. Among patients presenting with acute coronary syndrome and nonobstructive CAD by 
angiography, reduced CFR (assessed by invasive Doppler flow velocity monitoring) is associated with 
higher frequency of thin-cap fibroatheroma, greater plaque burden, and significantly higher levels of 
hsCRP, despite similar amounts of epicardial disease by luminal area and fractional flow reserve 
measurements15. These results reinforce previous observations16-18 that inflammation is associated with 
impaired coronary vasoreactivity and, in the appropriate patient population, may be a better marker for 
poor outcomes related to diffuse and/or microvascular CAD than are conventional ischemic 
assessments.  
Anti-inflammatory therapies can modulate CFR. There is preliminary evidence that anti-inflammatory 
therapies lead to improved CFR.  Indeed, treatment with statins in patients with dyslipidemia has been 
shown to improve CFR in a way that is modified among carriers of a specific polymorphism that reduces 
IL-1beta expression19. Short-term inhibition of IL-1 activity with the IL-1 receptor antagonist anakinra in 
rheumatoid arthritis patients without perfusion abnormalities has been shown to improve 
echocardiographic measures of LV myocardial deformation (by speckle tracking) and CFR (by Doppler 
flow velocity in the left anterior descending artery (LAD))20. Finally, treatment with methotrexate led to 
reduced clinical scores of disease severity and improved CFR (as measured by echo Doppler flow velocity 
in the LAD) in patients with early rheumatoid arthritis, with no effect on common carotid intima-medial 
thickness21.  
Coronary vascular dysfunction is a powerful predictor of clinical risk. Emerging data have consistently 
shown that CFR measurements by PET can distinguish patients at high risk for serious adverse events, 
including cardiac death8-11. We recently reported that reduced global CFR is independently associated 
with higher rates of cardiac and all-cause mortality in a large cohort of patients with and without DM8, 22. 
Relatively preserved CFR identifies patients with known or suspected CAD who have significantly lower 
risk of cardiac death, regardless of traditional semi-quantitative measures of stress-induced ischemia. 
Conversely, reduced CFR identifies patients at significantly higher risk of cardiac death, even among 
those without objective evidence of ischemia, probably due to diffuse atherosclerosis and/or 
microvascular dysfunction. PET measures of CFR improved risk stratification beyond comprehensive 
clinical assessment, LVEF and semi-quantitative measures of myocardial ischemia and scar, and led to 
clinically meaningful risk-reclassification of ~50% of intermediate risk patients8. Diabetics with impaired 
vs. preserved CFR experienced substantially higher cardiac mortality (7.6%/year vs. 1.3%/year, relative 
to 4.2%/year vs. 0.4%/year in nondiabetics, respectively, both p<0.0001)22. Importantly, diabetic 
patients without known CAD and with impaired CFR experienced a rate of cardiac death comparable to, 
and possibly higher than, that for nondiabetic patients with known CAD (Fig. 3). Measures of CFR 
integrate the hemodynamic effects of focal epicardial coronary stenosis, fluid dynamic effects of diffuse 
atherosclerosis, and the effects of coronary microvascular dysfunction, all of which are prevalent among 
diabetics23-25, and affected by systemic inflammation. These observations have implications for the 


 
4
classification of DM as a coronary disease risk equivalent26. Specifically, only among diabetics with 
impaired vascular function is prognosis comparable to nondiabetic patients with known CAD. Thus, 
differing levels of vascular health among previously studied cohorts may account for inconsistencies in 
relative mortality rates of diabetics without CAD and nondiabetics with CAD27-29.  
Quantitative CFR is a modifiable imaging biomarker of disease. There is consistent evidence supporting 
quantitative CFR as a powerful marker of vascular health and, as such, a useful marker to improve 
diagnosis and risk stratification and to monitor response to treatment, particularly in the context of 
clinical trials. The accuracy of quantitative noninvasive PET measures of myocardial blood flow and flow 
reserve by PET has been extensively validated in experimental animals30 and humans31-34. The 
reproducibility of this technique is also well-established33, 34. PET is considered the gold standard for 
quantifying coronary blood flow and flow reserve. There is extensive data supporting its use in diagnosis 
of CAD4, 35-37. The data discussed above demonstrate that the presence of abnormal CFR as measured by 
PET provides incremental risk stratification that leads to significant and meaningful risk-reclassification 
of intermediate risk patients5, 9-11, especially those with DM22. Furthermore, quantitative CFR as a 
measure of coronary vascular dysfunction is a modifiable imaging biomarker, which has been tested in 
the context of clinical trials 19, 38-46. 
 
Abacavir is a nucleoside reverse transcriptase inhibitor used as part of treatment regimens for HIV. An 
association between abacavir and increased myocardial infarction was first reported in 200847. Since 
then, most but not all studies have had similar findings48. As a result, HIV treatment guidelines state that 
ABC should be used with caution in patients with CV disease or at high CV risk. While the mechanism by 
which ABC increases CV risk is not definitively known, hypotheses include its effect on platelet 
aggregation, leukocyte adhesion, and systemic inflammation48. 
 
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 outcomes49, 50. 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. 
 
2.  
SPECIFIC AIMS  
2.1 
Hypothesis and Objectives 
The primary hypothesis of the B/F/TAF-CFR study is that reducing endothelial cell activation and 
dysfunction using bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in place of 
abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) will quantitatively improve coronary flow reserve as 
measured by PET over 24 weeks, in stable higher risk asymptomatic patients with HIV.  
 
The primary objective of the B/F/TAF-CFR study is to test the hypothesis that in stable HIV patients 
treated with abacavir/lamivudine/dolutegravir STR regimens, a switch to a single tablet regimen 
(B/F/TAF) will improve coronary flow reserve and myocardial tissue perfusion, as assessed by 
quantitative PET imaging. This is a prospective, single arm study in which we will test that treatment 
B/F/TAF orally daily for 24 weeks will result in improved global coronary flow reserve in response to 
adenosine, reflecting coronary vasodilator function, as compared to baseline.  
 


 
5
2.2 
Primary Endpoint: 
Change (from baseline) in global coronary flow reserve, as measured by PET imaging at 24 weeks after 
initiation of B/F/TAF therapy. 
 
2.3 
Secondary Endpoints: 
2.3.1. Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 
weeks after initiation of B/F/TAF; 
2.3.2. Change (from baseline) in peak-stress global coronary vascular resistance (in mm 
Hg/mL/min/g) at 24 weeks after initiation of B/F/TAF; 
2.3.3. Change in serum biomarkers of inflammation (hs-CRP, IL-6, sCD163 and sCD14), myocyte 
injury and strain (hs Troponin, NT-proBNP) at 24 weeks after initiation of B/F/TAF. 
 
3.  
SUBJECT SELECTION  
3.1. 
Study Design 
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. 
 
3.2. 
Study group: HIV patients on stable therapy with abacavir/lamivudine/dolutegravir STR 
regimens. 
3.2.1. Inclusion criteria: 
We will recruit 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, HGB >10 g/dl, or Glomerular Filtration Rate (GFR) >30 
that do not preclude the use of Biktarvy. 
 
3.2.2. 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 and breast-feeding;  


 
6
(8) 
Patients requiring medications contraindicated with the components of B/F/TAF; 
(9) 
Patients on active treatment for severe asthma or severe COPD; 
(10) Hepatitis B; 
(11) Any reported use of methamphetamine, cocaine and heroin within the past 6 months; if 
such use has been reported, a negative toxicology screen will be required before entry. 
 
3.2. Source of subjects and recruitment methods 
A total of 30 evaluable patients will be required. This will be a collaborative effort between 4 sites in the 
Boston area: (1) Brigham and Women’s Hospital, BWH (PI: Paul Sax, MD), (2) Boston Medical Center (PI: 
Nina Lin, MD), (3) Tufts Medical Center (PI: Laura Kogelman, MD), and (4) Massachusetts General 
Hospital (PI: Virginia Triant, MD). All patients will be referred for PET imaging to BWH, with BWH serving 
as the Core Imaging Lab and Data Coordinating Center (PI: Marcelo Di Carli, MD).  
 
4. SUBJECT ENROLLMENT  
 
4.1.  
Procedures for obtaining informed consent  
The Principal Investigator, co-investigator, or qualified PI designee at each site will obtain consent during 
the study-related hospital visit prior to any study-related procedures.  Consent of subjects who do not 
speak English will be obtained and documented following the procedures outlined by IRB policy at each 
recruiting site. The informed consent process will also be documented and added to the research files 
for this study. 
 
4.2. 
Methods of Enrollment 
Potential study subjects will be recruited from medical clinics at BWH, MGH, BMC, and Tufts Medical 
Center. Screening procedures will include queries for potentially eligible subjects from lists of patients 
who are followed at each site.  Investigators at each site will evaluate whether a patient might be a 
candidate for the study and follow site-specific protocols for approaching patients and invite them into 
the study.  We will make every effort to mitigate any undue influence on patients to participate in this 
study, including providing the informed consent document to the patient to take home.  The patient will 
then be instructed to reach out to the study team or other healthcare providers with questions at any 
time.  The PI or PI designee at each site will review the informed consent form with the patient and 
answer any additional question the patient may have. All PET/CTs will occur at BWH.  Treatment 
assignment and monitoring will be performed by each site.  Additional procedures, particularly at the 
Baseline and End of Treatment visits may be performed at the local site or at BWH, for the convenience 
of the subjects. 
 
4.3. 
Treatment assignment 
Study subjects will all receive one tablet daily of bictegravir 50 mg/emtricitabine 200 mg/tenofovir 
alafenamide 25 mg. 
 
5. STUDY PROCEDURES 
 
 


 
7
5.1.  Study visits and parameters to be measured 
This is a collaborative, multi-center, single arm trial. After giving written informed consent to participate 
in the study and fulfilling criteria for inclusion, patients will be switched to B/F/TAF and followed up for 
24 weeks. Patients will undergo rest and vasodilator-stress PET/CT scan for measurement of coronary 
flow reserve at baseline (before the switch to B/F/TAF), and again after completion of 24 weeks of 
B/F/TAF. Safety labs will be assessed at baseline at the 45-day study visit and at the end of the study at 
the Day 168 visit. There will be follow up phone calls at day 14, day 126, and one week after the end of 
study at day 174. Follow up calls will be used to assess changes in medical history and for any adverse 
event.  
Figure 1.  Outline of Procedures    
 
Table 1.  Schedule of Assessments   
Procedure 
Screening 
(-28 to -1 
days) 
Baseline 
(day 0) 
Tel F/U 1 
(day 14) 
Study 
Visit 
(day 45) 
Tel F/U 2 
(day 126) 
End of 
Treatment 
(day 168) 
Tel F/U 3 
(day 174) 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
Medical History 
 
X 
X 
X 
X 
X 
X 
Medication History 
 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
 
X 
 
X 
 
Physical Exam 
 
X 
 
X 
 
X 
 
Pregnancy Test + 
X 
X 
 
 
 
X 
 
Lab Tests (Clinical)  
X 
X 
 
X 
 
X 
 
Lab Tests – 
Research Only (to 
store) 
 
X 
 
 
 
X 
 
ECG 
 
X 
 
 
 
X 
 
PET/CT 
 
X 
 
 
 
X 
 


 
8
Study Drug 
Dispensed 
 
X 
 
X 
 
 
 
Study Drug Pill 
Count / Diary 
Collection 
 
 
 
X 
 
X 
 
AE Monitoring 
 
X 
X 
X 
X 
X 
X 
*Telephone follow-up calls and study visits will be +/- 7 days to allow for scheduling flexibility.  
**Day 45 study visit will be +/- 14 days to allow for scheduling flexibility. 
***Day 168 study visit will be +/- 7 days to allow for scheduling flexibility and to ensure adequate 
supply of study drug.  
+Screening Pregnancy test may be urine or serum 
 
Screening (-28 to -1 days) 
• 
All screening assessments will occur within 28 days prior to start of medication switch  
• 
Obtain informed consent 
• 
Note whether subjects have fasted for 4 hours prior to the visit  
• 
Review inclusion and exclusion criteria to ensure the patient is eligible 
• 
Obtain vital signs, including weight and height, systolic and diastolic blood pressure (BP), heart 
rate (HR) 
• 
Perform laboratory tests, including pregnancy test (if WOCBP) and hepatitis B.  Laboratory tests 
(excluding pregnancy is WOCBP) are valid within one year of the screening visit).  
 
Baseline (Day 0, just prior to study medication initiation) 
• 
Verify clinical stability since screening evaluation 
• 
Confirm that subjects have withheld caffeine for 12 hours and fasted for 4 hours prior to 
imaging tests 
• 
Confirm that subjects have withheld beta blockers, calcium channel blockers and arterial 
vasodilators for 24 hours prior to the PET scan 
• 
Obtain interim medical history and concomitant medications review 
• 
Obtain vital signs, including weight and height, systolic and diastolic blood pressure (BP), heart 
rate (HR), and oxygen saturation (O2 sat) 
• 
Obtain 12-lead ECG 
• 
Complete physical exam  
• 
Perform laboratory tests, including serum pregnancy test prior to any imaging 
• 
Perform PET/CT scan 
• 
Study medication initiation must occur within 10 days of the baseline evaluation 
• 
Provide subjects with study drug and diary to take until next study visit (Day 45) 
• 
Monitor for AEs.  Educate patients on most common side effects of the new drug (Table 3).  
They are encouraged to immediately contact study investigators/staff by email and/or phone for 
any new or concerning symptoms.    
 


 
9
Day 14 (Telephone follow-up call 1) 
• 
Contact all subjects by telephone approximately 2 weeks after medication switch 
• 
Assess changes in medical history or medication changes 
• 
Monitor for AEs 
 
Day 45 (study visit) 
• 
Assess drug compliance via pill count 
• 
Verify clinical stability since screening evaluation 
• 
Confirm that subjects have fasted for 4 hours prior to imaging tests 
• 
Obtain interim medical history and concomitant medications review 
• 
Obtain vital signs, including weight and height, systolic and diastolic blood pressure (BP), heart 
rate (HR), respiratory rate (RR), and oxygen saturation (O2 sat) 
• 
Complete physical exam  
• 
Perform laboratory tests 
• 
Collect drug remaining study drug and first diary to assess compliance 
• 
Prior to leaving, patients will be supplied with study drug and a new drug diary 
• 
Monitor for AE; subjects are again educated about the most common side effects.  They are 
encouraged to immediately contact study investigators/staff by email and/or phone for any new 
or concerning symptoms.   
 
Day 126 (Telephone follow-up call 2) 
• 
Contact all subjects by telephone approximately 18 weeks after medication switch 
• 
Assess changes in medical history or medication changes 
• 
Monitor for AEs 
 
Day 168 (End of Treatment) 
• 
Assess drug compliance via pill count 
• 
Verify clinical stability since screening evaluation; including specific inquiry regarding common 
dose-related side effects associated with B/F/TAF 
• 
Confirm that subjects have withheld caffeine for 12 hours and fasted for 4 hours prior to 
imaging tests 
• 
Confirm that subjects have withheld beta blockers, calcium channel blockers and arterial 
vasodilators for 24 hours prior to the PET scan 
• 
Obtain interim medical history and concomitant medications review 
• 
Obtain vital signs, including weight and height, systolic and diastolic blood pressure (BP), heart 
rate (HR), and oxygen saturation (O2 sat) 
• 
Obtain 12-lead ECG 
• 
Complete physical exam  
• 
Perform laboratory tests, including serum pregnancy test prior to any imaging 
• 
Collect remaining study drug and second drug diary to assess compliance 
• 
Perform PET/CT scan 


 
10
• 
Monitor for AEs 
 
Day 174 (Telephone follow-up call 3) 
• 
All patients will be contacted by telephone at approximately 7 days following administration of 
the last dose of study drug for AE monitoring. 
 
5.2. Drug to be used 
B/F/TAF is indicated for treatment of people with HIV-AIDS.  Patients enrolled in the study will be 
switched from a HIV regimen containing abacavir/lamivudine/dolutegravir to B/F/TAF for 24 weeks. In a 
comparative clinical trial, B/F/TAF was non-inferior to ABC/3TC/DTG in virologic outcomes and showed a 
significantly lower rate of patient-reported nausea. In Study GS-US-380-1489, a double-blind, 
multicenter, active-controlled, randomized controlled non-inferiority trial of ABC/3TC/DTG vs B/F/TAF in 
treatment naïve adults, both regimens were well tolerated. Adverse events leading to study 
discontinuation were noted in no participants in the bictegravir, emtricitabine, and tenofovir 
alafenamide group and 1% of participants in the dolutegravir, abacavir, and lamivudine group. Adverse 
events related to study drug were less common with bictegravir, emtricitabine, and tenofovir 
alafenamide than with dolutegravir, abacavir, and lamivudine (26% [n=82] vs 40% [n=127]), the 
difference being driven by a higher incidence of drug related nausea in the dolutegravir, abacavir, and 
lamivudine group (5% [n=17] vs 17% [n=55]; p<0.0001). 
 
5.3. Concomitant medications 
Only patients on stable HIV therapies will be included in the study. Because concurrent medications can 
potentially affect coronary blood flow and flow reserve (e.g., antihypertensive and oral hypoglycemic 
agents, statins), only patients on stable treatment for hypertension, diabetes and/or dyslipidemia will be 
included in the study. The following medications will be allowed provided they are neither initiated nor 
discontinued during the study period:  
• 
Aspirin; 
• 
Angiotensin-converting enzyme inhibitors and/or Angiotensin Receptor Blockers; 
• 
-blockers; 
• 
HMG –CoA Reductase Inhibitors (statins); 
• 
Nitroglycerin and long-acting nitrates; 
• 
Oral anti-diabetic medications and Insulin; 
• 
Stable hormone replacement therapy 
 
5.4. Procedures 
Positron Emission Tomography (PET): Regional and global myocardial blood flow will be assessed using 
PET imaging.  Clinical and research cardiac PET studies are routinely performed at BWH. The PET imaging 
team at BWH under Dr. Di Carli’s leadership consist of experienced imaging specialists and have a track 
record in research studies using PET. Di Carli has extensive experience in performing these procedures, 
quantifying myocardial blood flow and flow reserve, has published extensively on this topic, and runs an 
active core laboratory with experience in multi-center trials using imaging endpoints. PET scans will be 
performed using a whole body PET/CT scanner. Study participants will be asked to refrain from drinking 
caffeine-containing beverages and taking theophylline-containing medications for 12 hours before the 
PET study.  Calcium channel blockers, beta blockers, and arterial vasodilators will be withheld for 24 
hours prior to the PET scan.  Studies will be performed after 4 hours of fasting. 


 
11
Assessment of myocardial blood flow and coronary flow reserve: Regional myocardial blood flow (MBF) 
will be measured at rest and during vasodilator-stress with adenosine using 13N-ammonia as the flow 
tracer. 13N-ammonia is used in clinical and research studies and has been validated for the 
quantification of myocardial blood flow and coronary flow reserve. After transmission imaging and 
beginning with the intravenous bolus administration of 13N-ammonia (~20 mCi), list mode images will be 
acquired for 19 minutes. The patient will then undergo a standard infusion of adenosine (140 
mcg/kg/min) for 4 mins or regadenoson bolus injection (0.4 mg). Two mins into the adenosine infusion 
or one minute after the regadenoson bolus, a second dose of 13N-ammonia will be administered, and 
PET imaging collected in the same manner. Heart rate, blood pressure, and 12-lead electrocardiogram 
will be recorded at baseline, every minute during the infusion, and during 5 minutes after completion of 
the adenosine infusion or regadenoson injection.  
Analysis of PET data: Absolute MBF (in ml/g/min) will be computed from the dynamic rest and stress 
images using commercially available software (Corridor4DM; Ann Arbor, Michigan) and previously 
validated methods 33, 34. Automated factor analysis will be used to generate blood pool (arterial input 
function) and tissue time-activity curves. Regional and global rest and vasodilator-stress MBF will be 
calculated by fitting the 13N-ammonia time-activity curves to a two-compartment tracer kinetic model as 
described previously 33, 34. Per-patient global coronary flow reserve (CFR) will be calculated as the ratio 
of MBF at peak vasodilator-stress over that at rest for the entire left ventricle. This method for 
quantitation of MBF is highly reproducible. In the PET core laboratory at BWH, the intra-class correlation 
coefficient for CFR among four readers is 0.94 (95%CI 0.88-0.98), indicating excellent reproducibility5. 
 
Coordination of ancillary study and central imaging analyses. BWH will serve as the coordinating center 
and central imaging core laboratory for the proposed PET scans in the pilot study. Dr. Di Carli runs a very 
active core laboratory and, as mentioned above, has extensive experience in managing multi-site 
imaging trials. In this investigator-initiated study, BWH will sub-contract all clinical centers in the 
ancillary study.  
For the central analysis of the PET images, all imaging data will be stripped of patient identifiers and 
assigned a trial-specific identifier to maintain compliance with US regulatory requirements regarding 
protection of patient privacy. Drs. Di Carli and Sax will organize a bi-monthly teleconference including 
investigators and research coordinators from each clinical site to monitor, discuss, and troubleshoot 
recruitment and other issues that may arise during the conduct of the clinical trial.  
 
5.5. Data to be collected and timing of data collection 
At each of the study visits, a medical history with symptom assessment, medication review, vital signs, 
physical exam, and blood samples will be obtained. As described above, additional data from the PET/CT 
scan as well as EKG assessment will be obtained at baseline and at the end of treatment period. One 
week after completion of the trial, telephone follow-up will be conducted to assess for any adverse 
events.  
 
Laboratory analysis:  Clinical labs will be collected at the Screening, Baseline, Day 45, and End of 
Treatment visits as follows: 
• 
Screening:  Comprehensive metabolic panel, lipid panel, hs-CRP, HbA1c, CBC, HIV RNA, D-Dimer, 
Hepatitis B Surface Antigen 
• 
Baseline:  hs-troponin and NT-proBNP 
• 
Day 45:  Comprehensive metabolic panel, lipid panel, hs-CRP, HbA1c, CBC, HIV RNA, D-Dimer 


 
12
• 
End of Treatment:  Comprehensive metabolic panel, lipid panel, hs-CRP, HbA1c, CBC, HIV RNA, 
D-Dimer, hs-troponin, NT-proBNP 
• 
In addition, pregnancy tests will be performed (for women of child-bearing potential) at 
Screening and before each PET scan. 
 
6. BIOSTATISTICAL ANALYSIS  
 
6.1.  Identification of clinical sites participating in the proposed ancillary study. BWH, MGH, Boston 
Medical Center and Tufts Medical Center will participate in this pilot study.  
Based on the power calculations above and assuming a 20% effect size, the study will need to recruit 
approximately 30 patients, approximately 10 patients per site.  BWH may recruit up to 20 patients.  We 
believe that the proposed  study is reasonable and attainable. Dr. Sax is an experienced clinical 
investigator with a successful track record in HIV clinical trials. Di Carli is a recognized expert in 
quantitative PET and nuclear cardiology imaging, has published widely on these topics, and has 
extensive experience in conducting clinical trials using imaging endpoints51-54.  
 
6.2.  Power Analysis:  
The table below shows the sample size needed to reach 85% power for an effect size of 20-30% relative 
improvement in coronary flow reserve from baseline using a standard deviation of 0.7 at baseline and 
follow-up and a correlation of 0.7 between baseline and follow-up measurements. Effect sizes were 
calculated from a baseline mean CFR of 1.74, which is a conservative value derived from our previous 
measurement of CFR in patients with HIV referred for myocardial perfusion imaging with PET: 
 
Table 2. Power calculation 
Effect Size Mean CFR difference 
(TAF – Baseline) 
SD 
Total Sample Size 
(80% power) 
Total Sample Size 
(85% power) 
Total Sample Size 
(90% power) 
20% 
0.35 
0.7 23 
26 
30 
25% 
0.43 
0.7 16 
18 
21 
30% 
0.51 
0.7 12 
14 
15 
 
Using a total sample size of 30 evaluable patients and a two-tailed alpha of 0.05, there will be 85% 
power to detect an effect size of 20% relative improvement in coronary flow reserve from baseline, 
estimating a ~15% attrition rate between time of baseline and final PET. The 20% relative improvement 
in CFR is the effect size previously demonstrated in statin trials. 
 
6.3. Study endpoints 
Primary Endpoint: Change (from baseline) in coronary flow reserve, as measured by PET imaging at 24 
weeks post medication switch. 
Secondary Endpoints: 
(1) Change (from baseline) in peak-stress global myocardial blood flow (in mL/min/g) at 24 weeks after 
initiation of B/FTAF; 


 
13
(2) Change (from baseline) in peak-stress global coronary vascular resistance (in mm Hg/mL/min/g) at 
24 weeks after initiation of B/FTAF; 
(3) Change in serum biomarkers of inflammation (hs-CRP, IL-6, sCD163 and sCD14), myocyte injury and 
strain (hs Troponin, NT-proBNP) at 24 weeks after initiation of B/F/TAF. 
  
 
6.4. Statistical methods 
To test the central hypothesis, that reducing endothelial cell activation and dysfunction by substituting 
B/F/TAF for ABC/3TC/DTG will quantitatively improve coronary flow reserve as measured by PET over 24 
weeks, we will perform a paired t-test to assess the ∆CFR between baseline and follow-up for each 
subject.   
If a significant change in CFR after the switch is observed, we will perform secondary analyses of 
association between other markers of inflammation also implicated in atherosclerosis (hs-CRP, IL-6, 
sCD163 and sCD14) with ∆CFR.  Significance of associations with other inflammatory markers and ∆CFR 
will be adjusted using the Bonferroni correction.  
 
 
7. RISKS AND DISCOMFORTS  
7.1.  Blood sampling and intravenous catheter 
The risks and discomforts of drawing blood from a vein include the possibility of discomfort, pain, 
redness, bruising, or bleeding at the site of the blood draw, occasional feeling of lightheadedness, and 
rarely, infection or fainting. 
 
There are minor risks and discomforts associated with placement of an intravenous line for the PET scan, 
including the possibility of bleeding, pain, inflammation (redness and swelling), and leaking of contrast 
agent outside of the vein at the site of the IV. These problems are usually self-limited or require only 
minor treatments, such as application of an ice-pack or slight pressure for a few minutes. 
 
7.2.  Vasodilator stress 
Vasodilator-stress with regadenoson and adenosine, as will be performed in this study, has been used 
routinely for many years for evaluation of known or suspected coronary artery disease in conjunction 
with myocardial perfusion imaging. During the infusion of the vasodilator stress agent, the patient may 
experience flushing, chest pain/pressure, nausea, or lightheadedness. If significant symptoms are 
present, patients will be given aminophylline (reversal agent) IV to relieve these symptoms. There will 
be continuous monitoring of heart rate, blood pressure, and 12-lead ECG throughout the infusion and 
recovery. These procedures are routinely performed in patients with CAD, as those in the CIRT trial, and 
are considered safe. 
Regadenoson stress as performed in this study has been used routinely for many years for evaluating 
patients with known or suspected CAD. The most common side effects associated with the regadenoson 
bolus include: flushing, chest pain/pressure, shortness of breath, palpitations, headache, mild 
hypotension and heart block. These side effects are usually mild and self-limiting. If they are severe in 
intensity, aminophylline IV (1 mg/kg) will be given as per standard protocol. 


 
14
Subjects with a history of seizures may receive adenosine. The side effects associated with this product 
include: facial flushing, headache, sweating, palpitations, chest pain, hypotension, shortness of 
breath/dyspnea, chest pressure, hyperventilation, head pressure, lightheadedness, dizziness, tingling in 
arms, numbness, apprehension, blurred vision, burning sensation, heaviness in arms, neck and back 
pain, nausea, metallic taste, tightness in throat, and pressure in groin. Adenosine is administered as a 
continuous infusion over 4 minutes and administered in a dose of 0.14mg/kg/min.  The half-life of 
adenosine is less than 10 seconds.  If the patient is having symptoms the infusion can be stopped, no 
further medication is administered, and the symptoms would stop within seconds because the 
medication would already be cleared from the heart. Therefore, no reversal medication is needed.   
Rarely, an aminophylline IV injection may be used to reverse side effects of regadenoson infusion. 
Aminophylline is generally well tolerated; possible side effects of aminophylline may include nausea, 
headache, restlessness, convulsions, rapid breathing, a rapid heart rate, and allergic reactions such as 
rash. 
7.3.  Radiation risk 
The estimated whole body effective radiation dose from each of the 13N-ammonia PET scan is ~3-4 
mSv55, comparable to the annual radiation dose from background radiation sources in North America. 
Each subject will undergo 2 PET studies during the trial for a total dose of ~6-7 mSv, significantly lower 
than the average radiation exposure associated with a single conventional myocardial perfusion imaging 
study using single-photon emission computed tomography (SPECT)55. 
 
7.4.  Drug side effects and toxicities 
The most common side effects with the use of B/F/TAF are nausea, diarrhea, and headache, as 
described in Table 3 which is based on the results of the phase III trials49, 50.   
 
Table 3. Drug side effects 
 
B/F/TAF group 
(n=314) 
DTF/ABC/3TC group 
(n=315) 
Any adverse event (AE) 
265 (84%) 
283 (90%) 
Grade 3 or 4 AE 
19 (7%) 
25 (8%) 
Drug-related AE 
82 (26%) 
127 (40%) 
Drug-related serious AE 
0 
4 (<1%) 
Any AE leading to study drug 
discontinuation 
0 
4 (1%)* 
AE occurring with 5% incidence in either group 
Nausea 
32 (10%) 
72 (23%) 
Diarrhea 
40 (13%) 
41 (13%) 
Headache 
36 (11%) 
43 (14%) 
Upper respiratory tract infection 
20 (6%) 
34 (11%) 
Nasopharyngitis 
23 (7%) 
29 (9%) 
Fatigue 
19 (6%) 
27 (9%) 
Syphilis 
12 (4%) 
25 (8%) 


 
15
Insomnia 
14 (4%) 
20 (6%) 
Arthralgia 
11 (4%) 
19 (6%) 
Vomiting 
12 (4%) 
17 (5%) 
Cough  
20 (^%) 
8 (3%) 
Bronchitis 
10 (3%) 
16 (5%) 
Abdominal pain 
9 (3%) 
16 (5%) 
Data are in n (%). B/F/TAF=bictegravir, emtricitabine, and tenofovir alafenamide. DTG/ABC/3TC= dolutegravir, 
abacavir, and lamiduvine. *Chronic pancreatitis and steatorrhea (n=1), nausea and generalized rash (n=1), 
depression (n=1), and thrombocytopenia (n=1).49, 50 
 
7.5.  Reproductive risks 
Pregnant or breastfeeding patients will be excluded from this study.   
 
A female is considered of child-bearing potential unless: 
• 
Permanently sterile (includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) 
• 
Medically documented ovarian failure 
• 
Post-menopausal, defined as ≥ 60 years of age with cessation of menses for ≥ 12 months. 
7.6.  Unknown Risks: 
There may be other risks and side effects that are not known at this time. 
 
8. POTENTIAL BENEFITS  
8.1.  Potential benefits to participating individuals 
There are no direct benefits for the patient from taking part in this study. The proposed study will test 
the important question of whether reducing endothelial cell activation and dysfunction using B/F/TAF 
will quantitatively improve coronary flow reserve, a sensitive measure of myocardial ischemia. Thus, this 
pilot study will provide important and unique mechanistic insights of the capabilities of novel HIV 
therapies to improve key determinants of clinical risk (improve coronary blood flow and reduce 
ischemia) and, in so doing, improve patient symptoms and quality of life, as well as outcomes.  
 
8.2. Potential benefits to society 
Data collected in this pilot trial may provide important mechanistic insights into presumed 
cardiovascular benefits from novel HIV therapies, as well as into the pathophysiology of microvascular 
dysfunction in HIV-AIDS. 
 
9.  MONITORING AND QUALITY ASSURANCE  
 
9.1.  Safety monitoring 
The PI of the study will monitor the overall safety of the study and will report any adverse events to the 
IRB, per local institutional guidelines.  The PI will also monitor this study to ensure that subjects’ human 
rights, safety, and well-being are protected, that the study is properly conducted in adherence to the 
current protocol, and study data reported by the investigator/subinvestigator are accurate, complete 
and verifiable with study-related records such as source documents. 


 
16
Safety data will be obtained at each study visit from the spontaneous reports by patients of adverse 
events, vital sign monitoring, physical examinations, 12-lead ECGs and clinical laboratory tests. In 
addition, telephone follow-up will be conducted to assess for any adverse events. All safety data will be 
reviewed by an HIV physician investigator (Dr. Paul Sax). 
Patients with unexpected abnormalities on the baseline PET scan will be discussed with the patient’s 
PCP/ID physician to decide whether the patient should participate in this pilot trial. The findings will be 
discussed with the patient and the patient’s primary physician in order to facilitate an appropriate 
management plan. If a patient is excluded on safety grounds, we do not think that this will affect our 
ability to determine the effect of B/F/TAF on myocardial blood flow. 
The safety of B/F/TAF will be assessed with respect to the following end points: (1) death from any 
cause, (2) the composite of death from any cause or any cardiovascular hospitalization, (3) frequency of 
symptomatic documented arrhythmia, (4) serious adverse events related to the study drug and clinically 
significant laboratory abnormalities.  
 
9.2. Treatment Compliance 
Subject compliance to treatment regimen will be assessed at each study visit by a count of remaining 
medication in each bottle.  Subjects will be asked to complete a medication diary for additional 
compliance assessment.  The diary will be compared to the drug count.  A threshold of ≥80% will be 
used to define compliance with treatment assignment. Subjects determined to be noncompliant (<80% 
compliance) will be counseled regarding the importance of following dosing instructions but not 
withdrawn from the study.  
 
9.3. Discontinuation criteria for individual subjects  
Discontinued subjects are those who are enrolled in the study and for whom study treatment is 
terminated prematurely for any reason. The subject is free to withdraw from the study treatment 
and/or study for any reason and at any time without giving reason for doing so and without penalty or 
prejudice.  The investigator is also free to terminate a subject’s involvement in the study at any time if 
the subject’s clinical condition warrants it.  
Subjects will be discontinued if: 
• 
Subject experiences a serious or intolerable adverse event 
• 
Subject has severe disease and has to be intervened upon based on the imaging tests 
• 
In the Investigator’s opinion, the subject is non-compliant with the protocol requirements 
• 
Subject’s health would be jeopardized by continued participation 
• 
Subject wishes to withdraw consent 
• 
Investigator elects to end the study 
 
 
9.4. Adverse event reporting guidelines 
 
   9.4.1    Definition of Adverse Events (AEs) 
An adverse event (AE) is defined as any untoward medical occurrence in a subject administered a 
study drug, and which does not necessarily have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 


 
17
symptom, or disease temporally associated with the use of a study drug, whether or not related to 
the study drug. 
An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, 
physical exam) should be defined as an AE only if the abnormality meets one or more of the 
following criteria: 
• Induces clinical signs or symptoms 
• Requires active intervention 
• Requires interruption or discontinuation of study medication 
• The abnormality or investigational value is clinically significant in the opinion of the 
investigator 
 
   9.4.2    Definition of Serious Adverse Events (SAEs) 
A serious AE is any untoward medical occurrence that, at any dose: 
• Results in death, 
• Is life threatening (an event in which the subject is at risk of death at the time of the event; 
it does not refer to an event which hypothetically might have caused death if it was more 
severe), 
• Results in persistent or significant disability/incapacity, 
• Results in congenital anomaly, or birth defect, 
• Requires inpatient hospitalization or leads to prolongation of hospitalization 
(hospitalization for treatment/observation/examination caused by AE is to be considered 
as serious) 
• Other medically important events 
 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above. These events, 
including those that may result in disability, should also usually be considered serious.  
 
   9.4.3    Criteria for Causal Relationship to the Study Drug 
Adverse events that fall under either "Possible" or "Probable" should be defined as "adverse 
events whose relationship to the study drugs could not be ruled out." 
 
Causal relationship 
to the study drug 
Criteria for causal relationship 
 
Not Related 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship 
improbable, and/or in which other drugs, chemicals or underlying 
disease provide plausible explanations. 
Possible 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, but which 


 
18
could also be explained by concurrent disease or other drugs or 
chemicals.  Information on drug withdrawal may be lacking or unclear. 
Probable 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the drug, unlikely to be 
attributed to concurrent disease or other drugs or chemicals, and 
which follows a clinically reasonable response on re-administration (re-
challenge) or withdrawal (de-challenge). 
 
   9.4.4    Criteria for Defining the Severity of an Adverse Event 
The following standard with 3 grades is to be used to measure the severity of adverse events, 
including abnormal clinical laboratory values. 
• Mild: No disruption of normal daily activities 
• Moderate: Affect normal daily activities 
• Severe: Inability to perform daily activities 
 
   9.4.5    Reporting of Serious Adverse Events (SAEs) 
In the case of a serious adverse event (SAE), the investigator should submit a report to the IRB per 
local institutional guidelines of the date the investigator first becomes aware of the problem as 
per Partners policy.  
 
   9.4.6    Follow-up to Adverse Events 
All adverse events occurring during the study are to be followed up until resolved or judged to be 
no longer clinically significant, or until they become chronic to the extent that they can be fully 
characterized. 
If during adverse event follow-up, the adverse event progresses to an "SAE," or if a subject 
experience a new SAE, the investigator must immediately report the information to the sponsor. 
 
   9.4.7    Procedure in Case of Pregnancy 
If a woman becomes pregnant during the study dosing period or within 30 days from the 
discontinuation of dosing, the investigator will report the information to the IRB as if it is an SAE. 
The expected date of delivery or expected date of the end of the pregnancy, last menstruation, 
estimated fertility date, pregnancy result and neonatal data etc., should be included in this 
information. 
The investigator will follow the medical status of the mother, as well as the fetus, as if the 
pregnancy is an SAE.  
When the outcome of the pregnancy falls under the criteria for SAEs [spontaneous abortion, 
induced abortion, stillbirth, death of newborn, congenital anomaly (including anomaly in a 
miscarried fetus)], the investigator should respond in accordance with the report procedure for 
SAEs. Additional information regarding the outcome of a pregnancy (which is categorized as an 
SAE) is mentioned below: 
• "Spontaneous abortion" includes abortion and missed abortion. 
• Death of an infant within 1 month after birth should be reported as an SAE regardless of 
its relationship with the study drug. 


 
19
• If an infant dies more than 1 month after the birth, it should be reported if a 
relationship between the death and intrauterine exposure to the study drug is judged as 
"possible" by the investigator. 
• In the case of a delivery of a living newborn, the "normality" of the infant is evaluated at 
the birth. "Normality" of the miscarried fetus is evaluated by visual examination unless 
test results which indicate a congenital anomaly are obtained prior to miscarriage. 
 
 
 


 
20
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Hutchins GD, Schwaiger M, Rosenspire KC, Krivokapich J, Schelbert H and Kuhl DE. Noninvasive 
quantification of regional blood flow in the human heart using N-13 ammonia and dynamic 
positron emission tomographic imaging. J Am Coll Cardiol. 1990;15:1032-42. 
33. 
El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, Lahoud Y, Fischman A, Coughlan M, Yasuda 
T and Di Carli MF. Reproducibility and accuracy of quantitative myocardial blood flow assessment 
with (82)Rb PET: comparison with (13)N-ammonia PET. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine. 2009;50:1062-71. 
34. 
El Fakhri G, Sitek A, Guerin B, Kijewski MF, Di Carli MF and Moore SC. Quantitative dynamic cardiac 
82Rb PET using generalized factor and compartment analyses. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine. 2005;46:1264-71. 
35. 
Fiechter M, Ghadri JR, Gebhard C, Fuchs TA, Pazhenkottil AP, Nkoulou RN, Herzog BA, Wyss CA, 
Gaemperli O and Kaufmann PA. Diagnostic value of 13N-ammonia myocardial perfusion PET: 
added value of myocardial flow reserve. Journal of nuclear medicine : official publication, Society 
of Nuclear Medicine. 2012;53:1230-4. 
36. 
Murthy VL and Di Carli MF. Non-invasive quantification of coronary vascular dysfunction for 
diagnosis and management of coronary artery disease. J Nucl Cardiol. 2012;19:1060-72; quiz 1075. 
37. 
Parkash R, deKemp RA, Ruddy Td T, Kitsikis A, Hart R, Beauschene L, Williams K, Davies RA, Labinaz 
M and Beanlands RS. Potential utility of rubidium 82 PET quantification in patients with 3-vessel 
coronary artery disease. J Nucl Cardiol. 2004;11:440-9. 
38. 
Alexanderson E, Garcia-Rojas L, Jimenez M, Jacome R, Calleja R, Martinez A, Ochoa JM, Meave A 
and Alexanderson G. Effect of ezetimibe-simvastatine over endothelial dysfunction in dyslipidemic 
patients: assessment by 13N-ammonia positron emission tomography. J Nucl Cardiol. 
2010;17:1015-22. 
39. 
Baller D, Notohamiprodjo G, Gleichmann U, Holzinger J, Weise R and Lehmann J. Improvement in 
coronary flow reserve determined by positron emission tomography after 6 months of 
cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. Circulation. 
1999;99:2871-5. 
40. 
Guethlin M, Kasel AM, Coppenrath K, Ziegler S, Delius W and Schwaiger M. Delayed response of 
myocardial flow reserve to lipid-lowering therapy with fluvastatin. Circulation. 1999;99:475-81. 
41. 
Ilveskoski E, Lehtimaki T, Laaksonen R, Janatuinen T, Vesalainen R, Nuutila P, Laippala P, Karhunen 
PJ and Knuuti J. Improvement of myocardial blood flow by lipid-lowering therapy with pravastatin 
is modulated by apolipoprotein E genotype. Scand J Clin Lab Invest. 2007;67:723-34. 
42. 
Ling MC, Ruddy TD, deKemp RA, Ukkonen H, Duchesne L, Higginson L, Williams KA, McPherson R 
and Beanlands R. Early effects of statin therapy on endothelial function and microvascular 
reactivity in patients with coronary artery disease. Am Heart J. 2005;149:1137. 
43. 
McMahon GT, Plutzky J, Daher E, Bhattacharyya T, Grunberger G and DiCarli MF. Effect of a 
peroxisome proliferator-activated receptor-gamma agonist on myocardial blood flow in type 2 
diabetes. Diabetes Care. 2005;28:1145-50. 
44. 
Schelbert HR, Hassan A, Garner J and Di Carli MF. Effects of ACAT inhibition by positron emission 
tomography measured myocardial blood flow: A double-blind, randomized, multicenter trial. J Am 
Coll Cardiol (Abstract). 2003;41:460A. 


 
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45. 
Sdringola S, Gould KL, Zamarka LG, McLain R and Garner J. A 6 month randomized, double blind, 
placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion 
abnormalities by positron emission tomography in coronary artery disease. Am Heart J. 
2008;155:245-53. 
46. 
Garg R, Rao AD, Baimas-George M, Hurwitz S, Foster C, Shah RV, Jerosch-Herold M, Kwong RY, Di 
Carli MF and Adler GK. Mineralocorticoid receptor blockade improves coronary microvascular 
function in individuals with type 2 diabetes. Diabetes. 2015;64:236-42. 
47. 
Group DADS, Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, 
D'Arminio Monforte A, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN and Lundgren JD. Use 
of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected 
patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;371:1417-26. 
48. 
Alvarez A, Orden S, Andujar I, Collado-Diaz V, Nunez-Delgado S, Galindo MJ, Estrada V, Apostolova 
N and Esplugues JV. Cardiovascular toxicity of abacavir: a clinical controversy in need of a 
pharmacological explanation. AIDS. 2017;31:1781-1795. 
49. 
Sax PE, Pozniak A, Arribas J, Koenig E, Dejesus E, Stellbrink HJ, Antinori A, K. W, Slim J, Reynes J, 
Garner W, Sengupta D, Martin H, Quirk E and Cheng A. Phase 3 randomized, controlled clinical 
trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination (B/F/TAF) vs 
dolutegravir (DTG) + F/TAF in treatment-naïve HIV-1 positive adults: week 48 results. 
http://programmeias2017org/Abstract/Abstract/5793. 2017. 
50. 
Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar E, Wohl D, 
Rockstroh J, Wei X, White K, Martin H, Quirk E and Cheng A. A phase 3 randomized controlled 
clinical trial of bictegravir in a fixed dose combination, B/F/TAF, vs ABC/DTG/3TC in treatment-
naïve adults at week 48. http://programmeias2017org/Abstract/Abstract/5783. 2017. 
51. 
Di Carli MF, Charytan D, McMahon GT, Ganz P, Dorbala S and Schelbert HR. Coronary circulatory 
function in patients with the metabolic syndrome. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine. 2011;52:1369-77. 
52. 
Hachamovitch R, Johnson JR, Hlatky MA, Cantagallo L, Johnson BH, Coughlan M, Hainer J, 
Gierbolini J and Di Carli MF. The study of myocardial perfusion and coronary anatomy imaging 
roles in CAD (SPARC): design, rationale, and baseline patient characteristics of a prospective, 
multicenter observational registry comparing PET, SPECT, and CTA for resource utilization and 
clinical outcomes. J Nucl Cardiol. 2009;16:935-48. 
53. 
Hachamovitch R, Nutter B, Hlatky MA, Shaw LJ, Ridner ML, Dorbala S, Beanlands RS, Chow BJ, 
Branscomb E, Chareonthaitawee P, Weigold WG, Voros S, Abbara S, Yasuda T, Jacobs JE, Lesser J, 
Berman DS, Thomson LE, Raman S, Heller GV, Schussheim A, Brunken R, Williams KA, Farkas S, 
Delbeke D, Schoepf UJ, Reichek N, Rabinowitz S, Sigman SR, Patterson R, Corn CR, White R, 
Kazerooni E, Corbett J, Bokhari S, Machac J, Guarneri E, Borges-Neto S, Millstine JW, Caldwell J, 
Arrighi J, Hoffmann U, Budoff M, Lima J, Johnson JR, Johnson B, Gaber M, Williams JA, Foster C, 
Hainer J and Di Carli MF. Patient management after noninvasive cardiac imaging results from 
SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery 
disease). J Am Coll Cardiol. 2012;59:462-74. 
54. 
Dib N, Michler RE, Pagani FD, Wright S, Kereiakes DJ, Lengerich R, Binkley P, Buchele D, Anand I, 
Swingen C, Di Carli MF, Thomas JD, Jaber WA, Opie SR, Campbell A, McCarthy P, Yeager M, 
Dilsizian V, Griffith BP, Korn R, Kreuger SK, Ghazoul M, MacLellan WR, Fonarow G, Eisen HJ, 
Dinsmore J and Diethrich E. Safety and feasibility of autologous myoblast transplantation in 
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63. 


 
24
 

ICF_001.pdf: 
Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
Page 1 of 18 
 
Subject Identification 
Protocol Title: Effects of Bictegravir-Emtricitabine-Tenofovir Alafenamide on 
Coronary Flow Reserve in Stable HIV Patients (B/F/TAF-CFR) - Pilot Study 
 
Principal Investigator: Marcelo Di Carli, MD 
 
Site Principal Investigator: Virginia Triant, MD 
 
Description of Subject Population: Patients with Stable HIV 
 
About this consent form 
 
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form. 
 
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.” 
 
If you have any questions about the research or about this form, please ask us.  Taking part in 
this research study is up to you.  If you decide to take part in this research study, you must sign 
this form to show that you want to take part.  We will give you a signed copy of this form to 
keep. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
Why is this research study being done? 
 
We are doing this research study to find out if the drug called Biktarvy 
(Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)) can help improve the blood flow to 
the heart in people with HIV.  We think this is because Biktarvy reduces the inflammation in the 
heart arteries.  
 
Biktarvy is approved by the U.S. Food and Drug Administration (FDA) for treatment of HIV.  
BIKTARVY contains the medicines bictegravir, emtricitabine, and tenofovir alafenamide. 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 2 of 18 
 
Subject Identification 
This research study will compare the blood flow to your heart before starting Biktarvy and after 
24 weeks of taking the drug.  Biktarvy comes in tablet form and you will take it by mouth once a 
day.  
 
The gold standard for measuring blood flow to the heart with imaging is known as Positron 
Emission Tomography (PET).  A PET scan is a test that uses a radioactive tracer (dye) called 
N13 Ammonia.  PET scans allow doctors to see the blood flow to the muscle of the heart. It also 
lets us calculate the blood flow using a measure called Coronary Flow Reserve (CFR).  CFR 
adds information to help doctors diagnose heart disease.  The use of N13 for PET scans is  FDA-
approved and these scans are routinely performed at Brigham and Women’s Hospital. 
 
We are asking you to take part in this study because you have HIV and are currently taking 
abacavir/lamivudine/dolutegravir (Triumeq).  As part of your participation in this study, we will 
ask you to stop taking Triumeq for 24 weeks.  During this time, you will take Biktarvy, which 
will be provided by the study.  We believe that imaging studies such as PET will help doctors see 
if the Biktarvy has less effects on the heart than other HIV treatments.  
 
About 30 subjects will take part in this study. Subjects will be recruited from Brigham and 
Women’s Hospital as well as Massachusetts General Hospital, Tufts Medical Center, and Boston 
Medical Center. All research activities will be done at Brigham and Women’s Hospital.  
 
Gilead Sciences, Inc. is paying for this research to be done. 
 
 
How long will I take part in this research study? 
 
It will take you about 6 months to complete this research study.  During this time, we will ask 
you to make up to 4 study visits to the Brigham and Women’s Hospital. We will also call you 3 
times to remind you of your visits and see how you are feeling.  
 
 
What will happen in this research study? 
 
If you choose to take part in this study, we will ask you to sign this consent form before we do 
any study procedures. 
 
Any woman who is seeking to become pregnant or suspects she may be pregnant will not be 
enrolled in the study.  We will draw a blood sample to test for pregnancy at the screening visit 
and before each administration of radiopharmaceutical in this study, if you are a woman able to 
become pregnant.  


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 3 of 18 
 
Subject Identification 
 
 
 
Screening Visit (up to 4 weeks before the baseline visit) 
 
The screening visit will take about 1 hour.  During this visit, we will do some tests and 
procedures to see if you qualify for the study.  The study doctor will review the results of these 
tests and procedures.  At this visit we will: 
 
• Ask you questions about yourself to make sure you qualify for the study 
• Check your “vital signs” (blood pressure and heart rate, and oxygen saturation).  Oxygen 
saturation is how much oxygen is in your blood.  It is measured by a small device that is 
placed on your finger.  
• Let the study team know whether you have had any food for 4 hours prior to this visit. 
• Draw blood from you for testing. The blood test will include a pregnancy test if you are a 
woman who is able to become pregnant.  Pregnant and breast-feeding women cannot take 
part in this study.  We will also draw blood to make sure you do not have hepatitis B.  We 
will draw a total of about 26mL (approximately 5 teaspoons) of blood at this visit for 
clinical purposes.  If you have already had any of these tests done within the past year, 
we will use those results.  
• Possibly collect urine for a drug screen, which will test for the presence of recreational 
drugs.  The test results will be available to the study investigator and may be available to 
your doctor.  The results will not be entered in to your medical record, though positive 
results will disqualify you from participation. 
 
 
Baseline Visit (Day 0) 
 
 
This visit will take about 4 hours and will happen at the PET Imaging Center at BWH.  At this 
visit, we will: 
 
• Make sure that there have been no changes to your health since the screening visit. 
• Ask you about your medical history and any current medications you are taking. 
• Give you a physical exam, including height, weight and “vital signs” (blood pressure and 
heart rate, and oxygen saturation).  Oxygen saturation is how much oxygen is in your 
blood.  It is measured by a small device that is placed on your finger.  
• Do a 12-lead electrocardiogram (ECG).  An ECG is a test that checks the electrical 
activity of your heart.  We will place several small, sticky pads on your chest, arms, and 
legs.  Each pad has a wire attached.  The wires connect to a machine that makes a 
recording of your heart rhythm.  This painless test takes about 15 minutes.  


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 4 of 18 
 
Subject Identification 
• Draw blood from you for testing. The blood test will include a pregnancy test if you are a 
woman who is able to become pregnant.  Pregnant and breast-feeding women cannot take 
part in this study.  We will draw a total of about 9mL (approximately 2 teaspoons) of 
blood at this visit for clinical purposes and 29mL for research purposes if you agree, for a 
total of 38mL (approximately 8 teaspoons) at this visit. 
 
• Perform PET/CT scan 
 
PET/CT scan: 
• You must not have caffeine within 12 hours prior to this test and you must also not eat 
any food for 4 hours prior to this visit. 
 
• You will be instructed to not take your beta blockers, calcium channel blockers and 
arterial vasodilators for 24 hours prior to the PET scan.  We will help you identify any 
medications that fit one of these categories.  
 
• We will place an intravenous (IV) catheter, which is a thin, flexible plastic tube. 
 
• Adhesive patches will be placed on your chest to monitor your heart during the test. 
 
• You will be positioned in the PET/CT scanner.  You will lie on a table and will be moved 
through the circular opening of the donut shaped PET/CT scanner. The table will move 
forward and backward as the scan is done.  You will be asked to keep still during the 
scan.  We will inject you with the radioactive tracer through the IV to take pictures of 
your heart at rest.  These pictures take about 20 minutes.  
 
• We will take you out of the scanner and you will have about a 20-minute break.  
 
• You will be repositioned in the PET/CT camera again.  One of the doctors will give you a 
medication to dilate the vessels in the heart.  This injection will also be given through the 
IV.  You will then be injected with a second dose of the radioactive tracer to take pictures 
of your heart at stress.  These pictures will also take about 20 minutes. 
 
Before you leave the hospital, we will provide you with enough study drug to last you until your 
next visit (Study Visit, Day 45). 
 
How to take the study drug: 
1. The study drug comes in the form of a tablet.  You will take one (1) tablet a day. 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 5 of 18 
 
Subject Identification 
2. Please take note of the potential side effects of the study drug as listed on page 8.  
Immediately contact study investigators or staff by email and/or phone for any of these 
symptoms or any other new or concerning symptoms. 
3. Take the study drug by mouth, with or without food. 
4. Swallow the study drug tablet whole.  Do not crush, break, or chew the study drug tablets 
before swallowing. 
5. If you miss a dose of the study drug, wait to take the next dose of the study drug at your 
regular time.  Do not make up for the missed dose.  Record the date and the dose you 
miss on the medication diary provided by study staff.  
6. Do not take more than 1 dose at a time. 
7. If you take too much the study drug, call your doctor, or go to the nearest emergency 
room right away. 
 
We will give you a diary to record your daily intake of the study medication.  
 
Day 14 (Telephone follow-up call 1) 
 
This call will take less than 5 minutes.   
 
During this phone call we will: 
• Ask if you have made any changes to the medications you are taking.  
• Remind you to immediately contact study investigators or staff by email and/or phone for 
any of the symptoms list on page 8 or any other new or concerning symptoms. 
• Remind you to record your daily intake of the study medication on the diary.  
 
 
Day 45 (study visit) 
 
This visit will take about 2 hours and will happen at the PET Imaging Center at BWH.  At this 
visit, we will: 
 
• Ask you if you have been taking study drug as instructed by the study doctor. The study 
doctor or a member of the study staff will do a pill count from your drug bottle.  
• Ask you if you have experienced any side effects listed in this consent form. 
• Ask you about your medical history and any current medications you are taking. 
• Give you a physical exam, including height, weight and “vital signs” (blood pressure and 
heart rate, and oxygen saturation).  Oxygen saturation is how much oxygen is in your 
blood.  It is measured by a small device that is placed on your finger.  
• Confirm that you have not had any food for 4 hours prior to this visit. 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 6 of 18 
 
Subject Identification 
• Draw blood from you for testing.  We will draw a total of about 22mL of blood 
(approximately 4 teaspoons) at this visit for clinical purposes.   
• Before you leave the hospital, we will provide you with enough study drug to last you 
until your next visit (Study Visit, Day 168). 
 
We will give you a diary to record your daily intake of the study medication.  
 
Day 126 (Telephone follow-up call 2) 
 
This call will take less than 5 minutes.   
 
During this phone call we will: 
• Ask if you have made any changes to the medications you are taking.  
• Remind you to immediately contact study investigators or staff by email and/or phone for 
any of the symptoms list on page 8 or any other new or concerning symptoms. 
• Remind you to record your daily intake of the study medication on the diary.  
 
Day 168 (End of Treatment) 
 
This visit will take about 4 hours and will happen at the PET Imaging Center at BWH.  At this 
visit, we will: 
 
• Make sure that there have been no changes to your health since the Day 45 visit. 
• Ask you if you have been taking study drug as instructed by the study doctor. The study 
doctor or a member of the study staff will do a pill count from your drug bottle.  
• Ask you if you have experienced any side effects listed in this consent form. 
• Collect the diary 
• Ask you about your medical history and any current medications you are taking. 
• Give you a physical exam, including height, weight and “vital signs” (blood pressure and 
heart rate, and oxygen saturation).  Oxygen saturation is how much oxygen is in your 
blood.  It is measured by a small device that is placed on your finger.  
• Do a 12-lead electrocardiogram (ECG).  An ECG is a test that checks the electrical 
activity of your heart.  We will place several small, sticky pads on your chest, arms, and 
legs.  Each pad has a wire attached.  The wires connect to a machine that makes a 
recording of your heart rhythm.  This painless test takes about 15 minutes.  
• Draw blood from you for testing. The blood test will include a pregnancy test if you are a 
woman who is able to become pregnant.  Pregnant and breast-feeding women cannot take 
part in this study.  We will draw a total of about 26mL of blood (approximately 5 
teaspoons) at this visit for clinical purposes and 29mL (approximately 3 teaspoons) for 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 7 of 18 
 
Subject Identification 
research purposes if you agree, for a total of 55mL (approximately 8 teaspoons) at this 
visit. 
 
• Perform PET/CT scan 
 
 
 
PET/CT scan: 
• You must not have caffeine within 12 hours prior to this test and you must also not eat 
any food for 4 hours prior to this visit. 
 
• You will be instructed to not take your beta blockers, calcium channel blockers and 
arterial vasodilators for 24 hours prior to the PET scan.  We will help you identify any 
medications that fit one of these categories.  
• We will place an intravenous (IV) catheter, which is a thin, flexible plastic tube. 
 
• Adhesive patches will be placed on your chest to monitor your heart during the test. 
 
• You will be positioned in the PET/CT scanner.  You will lie on a table and will be moved 
through the circular opening of the donut shaped PET/CT scanner. The table will move 
forward and backward as the scan is done.  You will be asked to keep still during the 
scan.  We will inject you with the radioactive tracer through the IV to take pictures of 
your heart at rest.  These pictures take about 20 minutes.  
 
• We will take you out of the scanner and you will have about a 20-minute break.  
 
• You will be repositioned in the PET/CT camera again.  One of the doctors will give you a 
medication to dilate the vessels in the heart.  This injection will also be given through the 
IV.  You will then be injected with a second dose of the radioactive tracer to take pictures 
of your heart at stress.  These pictures will also take about 20 minutes. 
 
Day 174 (Telephone follow-up call 3) 
 
This call will take less than 5 minutes. We will call you by telephone at about 1 week (5 to 7 
days) after your last visit to see how you are feeling. 
 
 
What are the risks and possible discomforts from being in this research 
study? 
 
13N-Ammonia PET/CT Scan: 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 8 of 18 
 
Subject Identification 
 
As a result of your participation in this study you will be exposed to radiation from Nuclear 
Medicine scans of your heart. Please note that this radiation is not necessary for your medical 
care and is for research purposes only. The radiation you will receive from participation in this 
study is estimated to be 6 milliSieverts (mSv). A mSv is a unit of radiation dose. For comparison, 
everyone receives radiation exposure from natural background sources from the earth and the 
sky. The dose that you receive from participation in this research study is about the same as you 
would normally receive in 2 years from these natural sources.  
 
Scientists disagree on whether radiation doses at these levels pose significant health risks.  A 
possible effect that could occur at doses associated with this study is a slight increase in the risk 
of developing cancer later in life. 
 
If you have taken part in other research studies in the past 12 months that include tests with 
radiation, please tell us before you enroll in the study.  If your past radiation exposure is more 
than our current guidelines allow, you may not be able to take part in this study.  If you take part 
in a similar study involving radioactivity in the next 12 months, you should tell the doctor 
ordering the scans that you took part in this study. 
 
Please indicate below if you have taken part in research studies that have involved radiation 
exposure. 
 
 
___ YES, I have taken part in research studies that have involved radiation exposure within the 
last 12 months.  
 
INITIALS: _______ 
 
___ NO, I have not taken part in research studies that have involved radiation exposure within the 
last 12 months.   
 
INITIALS: _______ 
 
Biktarvy: 
 
Biktarvy, the study drug for this research study, is FDA-approved and is prescribed for the 
treatment of HIV.  
 
Very common side effects (more than 10 in 100): 
• Diarrhea 
• Headache  
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 9 of 18 
 
Subject Identification 
Common side effects (between 1 and 10 in 100): 
• Nausea  
• Vomiting 
• Stomach pain 
• Indigestion 
• Passing gas 
• Tiredness 
• Rash  
 
If you are infected with hepatitis B virus (HBV), there is a possibility of an unexpected worsening 
of hepatitis B if you stop taking Biktarvy. 
 
Do not take the following medications while you are in the study.  Taking these drugs and 
Biktarvy together may cause serious side effects: 
 
• Dofetilide 
• Rifampin 
• Any other medicines to treat HIV
For your safety during this study, call your study doctor BEFORE you take any: 
• new medications prescribed by your own doctor 
• other medications sold over-the-counter without a prescription 
• dietary or herbal supplements, antacids, laxatives, or vitamins  
 
Pregnancy: 
 
Radiation may cause physical or genetic damage to a fetus, so you should not participate in this 
study if there is a chance you may be pregnant or if you are breastfeeding.  
 
Regadenoson: 
 
 
Regadenoson stress as performed in this study has been used routinely for many years for 
evaluating patients with known or suspected CAD.  It is FDA approved.  The most common side 
effects associated with the regadenoson bolus include:  
 
Very common – more than 1 out of 10: 
• Flushing  
• Shortness of breath 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 10 of 18 
 
Subject Identification 
Common – between 1 and 10 out of 100: 
• Chest pain/pressure  
• Palpitations  
• Headache  
• Mild low blood pressure  
Uncommon - between 1 and 10 out of 1,000: 
• Heart block 
 
Adenosine: 
 
As part of the PET scan, you will receive a medicine called adenosine if you have a history of 
seizures. The side effects associated with adenosine include: 
 
Very common – more than 1 out of 10: 
• Facial flushing 
• Shortness of breath/dyspnea 
• Head pressure 
 
Common – between 1 and 10 out of 100: 
• Headache 
• Palpitations 
• Chest pain 
• Chest pressure 
• Hyperventilation 
• Nausea 
 
Uncommon - between 1 and 10 out of 1,000: 
• Sweating 
• Hypotension 
• Lightheadedness/ dizziness 
• Tingling in arms 
• Numbness 
• Apprehension 
• Blurred vision 
• Burning sensation 
• Heaviness in arms 
• Neck and back pain 
• Metallic taste 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 11 of 18 
 
Subject Identification 
 
Aminophyline: 
 
The study doctor may determine it is necessary to give you aminophyline if the regadenoson makes 
it harder for you to breath.  Aminophyline is FDA-approved to treat shortness of breath and other 
symptoms associated with breathing difficulties.  The most common side effects associated with 
aminophyline include:  
 
 
Uncommon - between 1 and 10 out of 1,000: 
• Nausea 
• Vomiting  
• Headache 
• Insomnia 
• High heart rate  
 
 
Blood Draws and Intravenous Catheter Risks 
 
You may have pain, bleeding, bruising, or infection at the place where we take blood samples or 
where we place the IV catheter. In the rare case that you develop a reaction, we will treat it 
immediately. 
 
We would like to store some of your samples and health information for future research related 
to heart disease and HIV.  We will label your samples and health information with a code instead 
of your name.  The key to the code connects your name to your samples and health information.  
The study doctor will keep the key to the code in a password protected database.  
 
Do you agree to let us store your samples and health information for future research 
related to heart disease and HIV? 
 
 Yes 
 No 
Initials___________ 
 
If later you change your mind and want your samples destroyed, contact the study doctor.  
 
 
Unknown Risks: 
 
There may be additional risks that are not known yet. 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 12 of 18 
 
Subject Identification 
What are the possible benefits from being in this research study? 
 
You may not benefit from taking part in this research study.  However, we believe that Biktarvy 
will have less side effects than abacavir/lamivudine/dolutegravir. 
 
Information learned from this study may help doctors diagnose heart disease in patients with 
HIV more accurately.  
 
 
What other treatments or procedures are available for my condition? 
 
Your Study Doctor will discuss appropriate treatment options and the risks and benefits with 
you. 
 
You can discuss if you want to have any treatment or if you want to choose other antiretroviral 
medications (ARVs) to treat your disease, which may include those that are already approved 
and sold.  
Instead of being in this study you have the choice of: 
• 
Treatment with other prescription drugs available to you such as Triumeq, 
(Abacavir/lamivudine, dolutegravir), Prezcobix (Darunavir/Cobicistat), Edurant 
(Rilpivirine), Raltegravir, Genvoya (Elvitegravir/cobicistat/tenofovir/emtricitabine). 
• 
Treatment with experimental drugs, if you qualify  
• 
No treatment 
 
 
Can I still get medical care within Partners if I don’t take part in this 
research study, or if I stop taking part?  
 
Yes.  Your decision won’t change the medical care you get within Partners now or in the future.  
There will be no penalty, and you won’t lose any benefits you receive now or have a right to 
receive. 
 
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  We will tell you if we learn new 
information that could make you change your mind about taking part in this research study. 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 13 of 18 
 
Subject Identification 
What should I do if I want to stop taking part in the study? 
 
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed. 
 
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed. 
 
 
Will I be paid to take part in this research study? 
 
We will pay you up to $500 including meals and parking vouchers if you complete the study.  If 
you do not complete the study, we will pay you as follows: 
 
Screening Visit: 
 
$50 
Baseline Visit: 
 
$200 
Day 45 Visit:  
 
$50 
End of Treatment Visit: 
$200 
 
TOTAL 
 
 
$500 
 
We will also give you a 6 to 24-hour parking voucher for all visits.  
 
 
What will I have to pay for if I take part in this research study? 
 
Study funds will cover the cost of all research-related study visits and for all procedures done for 
study purposes only. 
 
Although study funds will pay for certain study-related items and services, we may bill your 
health insurer for, among other things, routine items and services you would have received even 
if you did not take part in the research.  You will be responsible for payment of any deductibles 
and co-payments required by your insurer for this routine care or other billed care. 
 
If you have any questions about costs to you that may result from taking part in the research, 
please speak with the study doctors and study staff. 
 
 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 14 of 18 
 
Subject Identification 
 
 
 
What happens if I am injured as a result of taking part in this research 
study?
 
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer. 
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form. 
 
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the next section of this consent form. 
 
 
If I have questions or concerns about this research study, whom can I 
call? 
 
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.  
 
 
Marcelo Di Carli, MD is the person in charge of this research study.  You can call him at 617-
732-6291 M-F 9-5.  You can call Dr. Di Carli 24-hours a day/7 days a week by calling the BWH 
page operator at 617-732-5656 and asking to page Dr. Di Carli at pager #32505. 
 
If you have questions about the scheduling of appointments or study visits, call Laurel Campbell 
at 617-732-4237. 
 
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 857-282-1900. 
 
You can talk to them about: 
▪ Your rights as a research subject 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 15 of 18 
 
Subject Identification 
▪ Your concerns about the research 
▪ A complaint about the research 
 
Also, if you feel pressured to take part in this research study, or to continue with it, they want to 
know and can help. 
 
 
If I take part in this research study, how will you protect my privacy? 
 
During this research, identifiable information about your health will be collected.  In the rest of 
this section, we refer to this information simply as “health information.”  In general, under 
federal law, health information is private.  However, there are exceptions to this rule, and you 
should know who may be able to see, use, and share your health information for research and 
why they may need to do so.    
 
In this study, we may collect health information about you from: 
• Past, present, and future medical records 
• Research procedures, including research office visits, tests, interviews, and 
questionnaires 
 
Who may see, use, and share your identifiable health information and why they may 
need to do so: 
• Partners research staff involved in this study 
• The sponsor(s) of this study, and the people or groups it hires to help perform this 
research 
• Other researchers and medical centers that are part of this study and their ethics boards 
• A group that oversees the data (study information) and safety of this research 
• Non-research staff within Partners who need this information to do their jobs (such as for 
treatment, payment (billing), or health care operations) 
• The Partners ethics board that oversees the research and the Partners research quality 
improvement programs. 
• People from organizations that provide independent accreditation and oversight of 
hospitals and research 
• People or groups that we hire to do work for us, such as data storage companies, insurers, 
and lawyers 
• Federal and state agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health, and other US or foreign 
government bodies that oversee or review research)  


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 16 of 18 
 
Subject Identification 
• Public health and safety authorities (for example, if we learn information that could mean 
harm to you or others, we may need to report this, as required by law) 
• Other:        
 
Some people or groups who get your health information might not have to follow the same 
privacy rules that we follow and might use or share your health information without your 
permission in ways that are not described in this form.  For example, we understand that the 
sponsor of this study may use your health information to perform additional research on various 
products or conditions, to obtain regulatory approval of its products, to propose new products, 
and to oversee and improve its products’ performance.  We share your health information only 
when we must, and we ask anyone who receives it from us to take measures to protect your 
privacy.  The sponsor has agreed that it will not contact you without your permission and will not 
use or share your information for any mailing or marketing list.  However, once your information 
is shared outside Partners, we cannot control all the ways that others use or share it and cannot 
promise that it will remain private. 
 
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your health information. 
 
The results of this research study may be published in a medical book or journal, or used to teach 
others.  However, your name or other identifying information will not be used for these purposes 
without your specific permission. 
 
Your Privacy Rights 
 
You have the right not to sign this form that allows us to use and share your health information 
for research; however, if you don’t sign it, you can’t take part in this research study.    
 
You have the right to withdraw your permission for us to use or share your health information 
for this research study.  If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing.  Once permission is withdrawn, you cannot continue to 
take part in the study. 
 
If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others. 
 
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment.  To ask for this information, please contact the person in charge of this 
research study.  You may only get such information after the research is finished.  
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 17 of 18 
 
Subject Identification 
Informed Consent and Authorization 
 
Statement of Person Giving Informed Consent and Authorization 
 
▪ I have read this consent form. 
▪ This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study. 
▪ I have had the opportunity to ask questions. 
▪ I understand the information given to me. 
 
 
 
Signature of Subject: 
 
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above. 
 
 
 
 
 
 
 
 
Subject 
Date 
Time (optional) 
 
 
Signature of Study Doctor or Person Obtaining Consent: 
 
Statement of Study Doctor or Person Obtaining Consent 
 
▪ I have explained the research to the study subject. 
▪ I have answered all questions about this research study to the best of my ability. 
 
 
 
 
 
 
 
 
Study Doctor or Person Obtaining Consent 
Date 
Time (optional) 
 
 
 
 
 
 


Partners HealthCare System 
Research Consent Form 
 
 
 
General Template 
Version Date:  August 2016 
 
 
 
 
Page 18 of 18 
 
Subject Identification 
 
 
Consent of Non-English Speaking Subjects Using the “Short Form” in the 
Subject’s Spoken Language 
 
Statement of Hospital Medical Interpreter 
 
As someone who understands both English and the language spoken by the subject, I interpreted, 
in the subject's language, the researcher's presentation of the English consent form.  The subject 
was given the opportunity to ask questions. 
 
 
 
 
 
 
 
 
Hospital Medical Interpreter 
Date 
Time (optional) 
 
OR 
 
Statement of Other Individual (Non-Interpreter) 
 
As someone who understands both English and the language spoken by the subject, I represent 
that the English version of the consent form was presented orally to the subject in the subject’s 
own language, and that the subject was given the opportunity to ask questions. 
 
 
 
 
 
 
 
 
Name 
Date 
Time (optional) 
Consent Form Version:  08/23/2019