Bictegravir in the Elderly Living With HIV: Impact of Polypharmacy and Multimorbidity (BICEP)
Conditions: HIV-1-infection
Sponsor: State University of New York at Buffalo

 
 
Bictegravir in the Elderly Living with HIV: Impact of Polypharmacy and Multimorbidity 
 
 
 
 
 
 
 
 
 
 
 
Investigators: Qing Ma, PharmD, PhD, Allyssa Shon MD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version 1.0 
June 5, 2020

 
 
 
TEAM ROSTER 
 
 
Qing Ma, PharmD, PhD 
NYS Center of Excellence in Bioinformatics and Life Sciences 
Department of Pharmacy Practice 
University at Buffalo 
 
Allyssa Shon, MD 
Medical Director 
Evergreen Health 
Department of Medical  
School of Medicine and Biomedical Sciences 
University at Buffalo 
 
Fatai Gbadamosi, MD 
Senior Medical Director 
Evergreen Health 
 
Sibu Nair, MS 
Clinical Trials Administrator 
Evergreen Health 
 
Shih-Ping Lin, MD 
NYS Center of Excellence in Bioinformatics and Life Sciences 
Department of Pharmacy Practice 
University at Buffalo 
 
 

 
 
 
TABLE OF CONTENTS  
 
 
Page 
 
SCHEMA 
 
 
5 
1.0 INTRODUCTION  
1.1 Background 
1.2 Rationale 
1.3 Study Design 
1.4 Minimizing Risks to Subjects 
 
 
6 
7 
7 
9 
2.0 STUDY OBJECTIVES 
 
10 
3.0 SELECTION AND ENROLLMENT OF SUBJECTS 
3.1 Inclusion Criteria 
3.2 Exclusion Criteria 
10 
10 
10 
4.0 CLINICAL AND LABORATORY EVALUATIONS 
4.1 Screening and Entry Evaluations 
4.2 Evaluations During Treatment 
4.3 Premature Discontinuation 
4.4 Off-Drug Requirements 
11 
11 
13 
16 
16 
5.0 DATA COLLECTION AND ADVERSE EXPERIENCE REPORTING 
5.1 Records to be Kept 
5.2 Monitoring 
5.3 Serious Adverse Experience Reporting 
5.4 Safety Monitoring 
16 
16 
16 
17 
17 
 
6.0 STUDY TREATMENT 
6.1 Drug Regimens, Administration, and Duration 
6.2 Drug Formulations 
6.3 Drug Supply, Distribution, and Pharmacy 
6.4 Concomitant Medications 
6.5 Toxicity Management 
6.6 Criteria for Treatment Discontinuation 
17 
17 
18 
18 
18 
18 
19 
7.0 STATISTICAL CONSIDERATIONS 
7.1 General Design Issues 
7.2 Sample Size and Accrual 
7.3 Monitoring and Analysis 
 
 
 
 
 
 
 
 
19 
19 
20 
20 

 
 
TABLE OF CONTENTS (Cont.) 
 
 
Page 
 
8.0 HUMAN SUBJECTS 
8.1 Institutional Review Board (IRB) Review and Informed Consent 
8.2 Data storage and Subject Confidentiality 
8.3 Costs to the Subjects 
8.4 Compensation for Participation 
8.5 Study Discontinuation 
 
20 
20 
21 
21 
21 
21 
9.0 PUBLICATION OF RESEARCH FINDINGS 
 
21 
10.0 BIOHAZARD CONTAINMENT 
 
21 
11.0 REFERENCES 
22 
 
 
 
 
 
 

 
 
SCHEMA 
Bictegravir in the Elderly Living with HIV: Impact of Polypharmacy and Multimorbidity  
 
 
DESIGN:                       Prospective, open-label, single center switch study 
 
SAMPLE SIZE:             160 evaluable HIV-infected subjects on GenvoyaTM or StribildTM 
 
REGIMEN: 
              The project will have two phases: screening and treatment.  
 
 
 
 
   Screening:  
HIV-infected subjects will be screened and enrolled into polypharmacy (PP, 
n=80) and non-PP groups (n=80). Baseline assessment will be performed.   
 
 
 
 
   Treatment:  
   Days 1-168: Administer bictegravir/emtricitabine/tenofovir alafenamide 
(BIC/FTC/TAF), containing 50 mg BIC, 200 mg FTC and 10 mg 
TAF single-tablet regimen, PO q day 
   Day 28: Week-4 assessment 
   Day 56: Week-8 assessment 
   Day 84: Week-12 assessment    
 
 
 
   Day 168: Week-24 assessment  
 
STUDY DURATION:     24 Weeks  
 
OBJECTIVES:  
 
 
 
 
 
 
 
 
 
 
ENDPOINTS:  
. 
 
 
 
 
 
 
Primary: 
1. Describe a decrease in PDDI when switched from GenvoyaTM or 
StribildTM to BIC/FTC/TAF in polypharmacy and non-
polypharmacy subjects; 
2. Determine the impact of PDDI reduction on health-related 
quality of life. 
Secondary: 
1. Determine adherence to BIC/FTC/TAF; 
2. Determine changes in blood pressure, glucose, and lipid profiles 
after the switch.  
 
Primary: 
1. Incidence of PDDI prior to and after the switch  
2. Health related quality of life assessments at baseline, week 12, 
and week 24.  
Secondary: 
1. Adherence at baseline, week 4, week 8, week 12, and week 24; 
2. Lipid panel, blood pressure and blood glucose levels at 
baseline, week 12, and week 24 

 
 
1.0 
INTRODUCTION 
 
1.1 
Background 
Antiretroviral treatment consisting of integrase strand inhibitors (INSTI) in combination 
with two nucleoside reverse transcriptase inhibitors (NRTIs) has become the standard 
of therapy for HIV-1 infected patients (2017 DHHS Guidelines)1. The development and 
advancement of such therapy have resulted in improved prognosis, allowing a larger 
proportion of patients in United States (> 50%) with HIV-1 infection to be 50 years of 
age or older, which is defined by the CDC as “older adults”2. A novel INSTI, bictegravir, 
has been recently approved by FDA, available in a fixed dose combination with 
emtricitabine (FTC) and tenofovir alafenamide (TAF) as a novel single-tablet regimen 
(STR), BIKTARVY®. Similar to other INSTI, bictegravir prevents HIV replication by 
inhibiting HIV integration into the host cell. In vitro studies have shown its selectivity 
against HIV-1 infected cells with a low cytotoxic profile3.  
  
Elvitegravir, boosted with cobicistat, is currently available as part of a single-tablet 
formulation with FTC and TAF (GenvoyaTM) or with FTC and TDF (StribildTM). Unlike 
ritonavir, cobicistat has no antiretroviral activity, but has potent inhibitory effects on 
CYP3A44. Elvitegravir is primarily metabolized by CYP3A4 and its co-administration 
with cobicistat boosts elvitegravir plasma concentration and prolongs its half-life4.  
Concurrent use of a potent CYP3A4 inhibitor, e.g., cobicistat, with medications that are 
metabolized by CYP3A4 can significantly increase the risk of drug-drug interactions.  
With an increase in the average survivability age of HIV-infected patients, chances of 
polypharmacy due to multimorbidity, a term used to define the presence of two or more 
concurrent chronic medical conditions, increases5. Two studies have demonstrated that 
older HIV+ individuals engaged in polypharmacy are more likely to experience potential 
drug-drug interactions (PDDI). Many chronic medications such as antidepressants, 
HMG-CoA reductase inhibitors (statins), and cardiovascular medications are 
metabolized by CYP3A4. Concurrent administration of these medications with 
GenvoyaTM and StribildTMcan lead to increases in PDDI. Such interactions can result in 
more adverse drug reactions, drug-related toxicity of narrow therapeutic index drugs, 
and variations in the efficacy of concurrent medications. However, unlike elvitegravir, 
bictegravir does not require a booster such as cobicistat for pharmacokinetic 
enhancement. Its use can result in reductions in PDDI caused by cobicistat in adults 
with polypharmacy. This can improve quality of life in general, adherence and can 
directly avoid DDI-related adverse effects6,7. 
 
Although antiretroviral therapy (ART), when used concurrently with certain 
medications, has an increased risk of PDDI, studies have suggested a low DDI profile 
of bictegravir3,8. In this study, such benefits of bictegravir will be assessed through the 
evaluation of polypharmacy, PDDI, health-related quality of life, and adherence9,10 of 
HIV-infected subjects. 
 
1.2 
Rationale 
The goals of the study are to 1) evaluate the probability of PDDI when switched from 
GenvoyaTM (E/C/F/TAF) or StribildTM (E/C/F/TDF) to bictegravir/emtricitabine/tenofovir 
alafenamide (BIC/FTC/TAF) in polypharmacy adults, and 2) to determine the impact of 
BIC/FTC/TAF therapy on health-related quality of life and adherence. No published 
studies have addressed the following questions: 1) Is there a reduction in PDDI in 
polypharmacy HIV-infected adults when switched from a cobicistat containing regimen 
such as GenvoyaTM to BIC/FTC/TAF? 2) What is the impact of polypharmacy on the 
health-related quality of life and on adherence in HIV-patients on BIC/FTC/TAF 
therapy? Current medical literatures have identified polypharmacy as one of the 

 
 
predictors for the occurrence of potential drug interactions. The risk of potential drug 
interaction increases from 39% to 100% when patients are on more than six 
medications compared to when they are on 2-3 medications. Through an established 
collaborative network, we will address these questions in a prospective, open-label 
treatment trial of stable HIV-infected subjects currently on GenvoyaTM or StribildTM 
switching to BIC/FTC/TAF. 
 
BIC/FTC/TAF related adverse drug events are possible in the study. Due to 
bictegravir’s recent FDA approval, a comprehensive list on the possible adverse drug 
events has become available. Common side effects reported in clinical phase II and 
phase III studies include diarrhea, nausea, and headache12. Serious adverse events, 
including lactic acidosis, severe hepatomegaly have been reported with nucleoside 
reverse transcriptase inhibitors, but are uncommon. The standard regimen of 
BIC/FTC/TAF will be used; if a regimen change occurs, participation in the study will be 
discontinued. Participants will be carefully screened and those with pre-conditions, 
such as morbid obesity, hepatitis B virus, hepatitis C virus co-infection will be 
documented in the study.  
 
1.3 
Study Design  
HIV-1 infected subjects on GenvoyaTM or StribildTM will be the study population. We will 
screen and enroll subjects. All subjects will switch from GenvoyaTM or StribildTM to 
BIC/FTC/TAF. Initial recruitment will occur after the IRB approval of this protocol.  
 
1.3.1 Among 1,377 HIV+ patients at Evergreen Health, 96% (n=1,323) are currently 
receiving ART.  The common regimens include protease inhibitors (n=303, 
23%), integrase inhibitors (n=779, 59%), efavirenz or daily nevirapine (n=340, 
26%).  The demographics of patients on GenvoyaTM and StribildTM are 
summarized as follows: 
 
Table 1. Demographics of patients on GenvoyaTM or StribildTM in Evergreen Health 
 
 
 
 
 
 
 
 
 
 
 
 
1.3.2 The patients with or without polypharmacy were summarized as Table 2.  
 
Table 2. Polypharmacy (PP) in patients on GenvoyaTM or StribildTM in Evergreen Health 
PP (w/HM) nPP (w/HM) PP (w/o HM) nPP (w/o HM) 
Total n=191 # (%) 
165 (86) 
26 (14) 
112 (59) 
79 (41) 
Age <50, n=107, # (%) 
84 (79) 
23 (21) 
50 (47) 
57 (53) 
Age >=50, n=84, # (%) 
81(96) 
3 (4) 
62 (74) 
22 (26) 
PP: polypharmacy; nPP: non-polypharmacy; defined as ≥5, HM: HIV medications 
 
1.3.3 Schematic outline of the protocol is below 
 
< 50 Years of 
Age  
 50 Years of 
Age 
Total 
Gender 
 
 
 
Male 
132 
94 
226 
Female 
40 
27 
67 
 
172 
121 
293 
Current Single Tablet Formulation Containing Integrase Inhibitor 
GenvoyaTM 
118 
87 
205 
StribildTM 
54 
34 
88 
Total 
172 
121 
293 

 
 
 
1.3.4 The diagnosis of multimorbidity will be based upon clinical assessments and 
documentation from the electronic medical record database. Polypharmacy 
data with a focus on the total number and category of prescriptions medications 
corresponding to each multimorbidity will be collected throughout the study. 
PDDI will be particularly evaluated between cobicistat and cardiovascular, 
dyslipidemia, diabetes, psychiatric and other comorbidity-based medications. 
The probability of polypharmacy related PDDI risk will be evaluated using a 
software program based on the Drug Interaction and Probability Scale (DIPS) 
and current evidence12. The Contraindications and Drug Interactions sections of 
GenvoyaTM, StribildTM and BIC/FTC/TAF monograph will be reviewed for PDDIs.  
PDDIs will be classified using categories defined by the University of Liverpool 
HIV Pharmacology Group6,8. “Red flags” will be combinations that are 
contraindicated or not to be coadministered. “Orange flags” include 
 
  
Screening 
BL 
Week 
4 
Week 
8 
Week 
12  
Week 
24 
Discontinuation Visit 
Time window (Day) 
-42 to -1 
0 
21-35 
49-63 
77-91 
161-
175 
  
Informed consent (including 
eligibility assessment) 
x 
 
 
 
 
 
Full assessment 
 
x 
 
 
x 
x 
x 
   HIV 20-Item Symptom Index 
 
x 
 
 
x   
x 
x 
   SF-12  
 
x 
 
 
x   
x 
x 
Study drug dispensing 
(^including adherence 
assessment) 
 
x 
x^ 
x^ 
x^ 
x^ 
 
Safety assessment (ADR) 
 
 
x 
x 
x 
x 
x 
Laboratory Assessments 
 
 
 
 
 
 
 
Blood 
  
  
  
  
  
  
 
   Resistance Testing* 
 
  
x 
x 
x 
x 
 
   HCV 
x 
  
  
  
  
  
 
   HBV 
x 
  
  
  
  
  
 
   RPR 
x 
  
  
  
  
  
 
   CD4+ 
x 
 x 
x 
  
x 
x 
 
   Hematology 
x 
  
x 
  
  
x 
 
Chemistry (incl. liver func. & 
lactate) 
x 
  
x 
  
  
x 
  
Prothrombin Time 
x 
  
x 
  
  
x 
 
Plasma HIV RNA 
x 
x 
x 
 x 
x 
x 
 
Chemistry (inc. albumin)  
  
x 
x 
  
  
x 
 
Complete blood cholesterol 
 
 
 
 
 
 
 
    HDL Levels 
 
x 
 
 
 
x 
 
    LDL Levels 
 
x 
 
 
 
x 
 
Triglycerides  
 
x 
 
 
 
x 
 
Total Cholesterol  
 
x 
 
 
 
x 
 
Blood Glucose 
 
x 
x 
 
x 
x 
 
Vitals 
x 
x 
x 
x 
 
x 
 
Urine 
  
  
  
  
  
  
 
   Urine drug screen 
  
x 
x 
  
  
x 
 
   Urinalysis 
x 
x 
x 
  
  
x 
 
   hCG* 
x 
x 
x 
 x 
 X 
x 
 
BL= Baseline; SF-12: short form health survey; *if indicated  
 
 
 

 
 
combinations that should not be coadministered, could be given with dose 
adjustment or increased monitoring, or have not been studied for safety, 
efficacy, or clinical significance. An expert pharmacist will approve the product 
monograph abstraction instructions and review any unclear PDDIs. Product 
monographs for non-ARV medications will not be reviewed, and interactions 
among non-ARVs will not be studied.  
 
1.3.5 Adherence will be assessed by pharmacy refills and pill count.  
 
1.3.6 Health-related quality of life will be evaluated primarily using the 20-question 
HIV Symptom Index (HSI) for symptom distress, originally designed by the 
AIDS Clinical Trials Group (ACTG)13,14. The HSI is strongly associated with the 
physical and mental health summary scales of the MOS-HIV measure, disease 
severity, and is independent of CD4 cell count and viral load. Short form health 
survey (SF-12) will also be used to measure the impact of HIV infection on 
subject’s health related quality of life.  
 
1.4 
Minimizing Risks to Subjects  
 
Risks and reported adverse events of BIC/FTC/TAF will be clearly explained to each 
subject during the informed consent process. At each study visit, the study nurse will 
ask participants to report any symptoms they experience while taking BIC/FTC/TAF. 
Participants will be instructed to contact the Clinical Trials Unit in the event of adverse 
events by telephone 24 hours a day/7 days a week. Following a telephone interview, 
the Clinical Trials Unit will schedule a visit for an additional assessment as necessary. 
For serious adverse events, participants will be instructed to immediately discontinue 
BIC/FTC/TAF and to go the closest emergency room. Any Grade 3 or higher symptoms 
or laboratory abnormalities will result in termination of BIC/FTC/TAF. Subjects who 
experience renal function abnormalities with estimated creatinine clearance below 30 
ml/min will also have the study drug terminated and complete the evaluations listed in 
Section 4.2. Subjects will also have the study drug terminated in cases of suspected 
drug-related toxicity, taking prohibited concomitant medications (see section 6.4.2), if a 
female subject is pregnant or breast-feeding, if the subject is judged by the 
investigators to be at significant risk of failing to comply with the provisions of the 
protocol as to cause harm to self or seriously interfere with the validity of the study 
results, at the discretion of the investigator, institutional review board (IRB), FDA, 
pharmaceutical sponsor; or if the subject requests to withdraw from the study. In case 
of injury or serious adverse events, the investigators will assist the subject in obtaining 
appropriate medical treatment. 
 
 
2.0 
STUDY OBJECTIVES 
 
2.1 
Primary 
 
2.1.1 Describe a decrease in PDDI when switched from GenvoyaTM or StribildTM to 
BIC/FTC/TAF in polypharmacy and non-polypharmacy subjects. 
2.1.2 Determine the impact of PDDI reduction on health-related quality of life.  
 
2.2 
Secondary  
 
 
2.2.1 Determine adherence to BIC/FTC/TAF. 

 
 
 
2.2.2 Determine changes in blood pressure, glucose and lipid profiles after the switch 
 
3.0 
SELECTION AND ENROLLMENT OF SUBJECTS  
 
Recruitment of Subjects  
 
HIV-1 infected subjects will be recruited via IRB-approved posters and flyers and 
advertisements in local publications. IRB-approved flyers will also be posted in 
approved areas of the Evergreen Health. All necessary precautions will be taken to 
ensure participants confidentiality. Participants will be informed in the informed consent 
document that their participation shall be confidential and their information shall be 
protected. 
 
 
3.1 
Inclusion Criteria 
 
 
 
3.1.1 Adult individuals > 18 years of age.  
 
3.1.2 Able and willing to provide informed/signed consent. 
 
3.1.3 Presence of HIV-1 infection as documented by a licensed ELISA test kit and 
confirmed by Western blot or HIV RNA. 
 
3.1.4 Current antiretroviral therapy, GenvoyaTM or StribildTM for HIV-1 infection. 
 
3.1.5 At least 1 or more concurrent prescription medication. 
 
3.1.6 HIV VL < 50 for over 6 months, no current OI, no cancers 
 
3.2 Exclusion Criteria  
 
3.2.1 Use of drugs of abuse or alcohol which would interfere with adherence or 
completion of this study.  
 
3.2.2 Current antiretroviral therapy other than GenvoyaTM or StribildTM for HIV-1 
infection.  
 
3.2.3 Pregnancy or breast-feeding. Women of childbearing potential must have a 
negative serum or urine pregnancy test within 14 days prior to study entry and 
day of entry. 
 
3.2.4 Chronic, severe, or other medical conditions that, in the opinion of the 
investigator, would interfere with the subject’s ability to participate in the 
protocol. 
 
3.2.5 Use of prohibited protocol-specified drugs, prescription or over-the-counter 
medication (see Section 6.4.2) within 14 days prior to study entry. 
 
3.2.6 Moderate or severe cognitive impairment by history that, in the opinion of the 
investigator, would interfere with the subject’s ability to participate in the 
protocol 
 
3.2.7 Laboratory parameters documented within 21 days prior to study entry that 
would increase the risk for adverse events: 

 
 
a. Hemoglobin < 12.5 g/dL for men; < 11.5 g/dL for women; 
b. Platelet count < 100,000 platelets/mm 3; 
c. AST (SGOT) or ALT (SGPT) > 1.5 x the upper limit of normal (ULN); 
d. Estimated GFR < 30 ml/min 
 
 
4.0 
CLINICAL AND LABOATORY EVALUATIONS 
 
Signs and symptoms, laboratory results, and toxicities ≥ Grade 3 will be recorded on the 
appropriate case report forms (CRFs).  
 
4.1 
Screening and Entry Evaluations  
 
4.1.1 Screening evaluations will occur within 42 days of study entry  
 
4.1.1.1 
Details of the study will be carefully discussed with subjects during 
screening and the subject will be asked to read and sign an informed 
consent approved by the IRB at Evergreen Health.  
 
4.1.1.2 
Demographic information will be collected including age, sex, 
ethnicity, substance use, education, and employment.   
 
4.1.1.3 
Documentation of HIV infection, as specified in Section 3.1.2 prior to 
study entry. 
 
4.1.1.4 
Brief medical history will be obtained and will include:  
 
4.1.1.4.1 Previous diagnosis including liver disease, renal disease, 
fracture, osteoporosis, allergies, drug reactions, and most 
recent menses.  
 
4.1.1.4.2 Current prescription and non-prescription medications taken 
within 14 days prior to entry.   
 
4.1.1.4.3 Antiretroviral drug exposure within 1 month prior to entry. 
 
4.1.1.4.4 Recent use of drugs of abuse or unprotected sexual 
contacts. Past use of needles.  
 
4.1.1.4.5 A signs-and-symptoms assessment, including: vital signs, 
height, and weight. Vital signs will include temperature, blood 
pressure, and pulse rate.  
 
 
4.1.1.5 
The following laboratory tests must be performed within 42 days 
prior to study entry, unless otherwise noted: (This is for the times 
when there is no recent blood work done.)  
 
4.1.1.5.1 Hematology: hemoglobin, hematocrit, mean corpuscular 
volume (MCV), white blood cell count, differential white blood 
cell count, and platelet count.  
 

 
 
4.1.1.5.2 Blood chemistries: electrolyte, blood urea nitrogen (BUN), 
creatinine, creatine kinase, glucose, phosphorus, amylase, 
lactate, and calcium.  
 
4.1.1.5.3 Liver function tests: total bilirubin, AST, ALT, alkaline 
phosphatase, and albumin.  
 
4.1.1.5.4 Coagulation: prothrombin time, international normalized ratio, 
partial thromboplastin time.  
 
4.1.1.5.5 Urinalysis, including urine glucose and protein.  
 
4.1.1.5.6 Estimated glomerular filtration rate (eGFR)  
 
4.1.1.5.7 For women of childbearing potential: Serum or urine 
pregnancy test.  
 
4.1.1.5.8 HIV RNA in blood plasma.  
 
4.1.1.5.9 Lymphocytes subset in blood (including CD4+ and CD8+ T-
cell absolute counts and percent).  
 
4.1.1.5.10 Hepatitis C and hepatitis B serological testing  
 
4.1.1.5.11 Rapid plasmin reagent (PRP)  
 
4.1.1.5.12 Drug resistance mutation genotyping in blood. If available, 
records documenting same can be obtained from Primary 
Care Physician in place of performing the drug resistance 
mutation genotyping.  
 
 
4.1.2 Baseline (Entry) Evaluation: Within 42 days of the screening evaluation, eligible 
and consenting subjects will enter the study. Additional assessments will be 
performed and study drug will be dispensed.  
 
4.1.2.1 
A complete medical history and physical examination will be 
performed:  
 
4.1.2.1.1 Prior diagnoses including liver disease, renal disease, 
fracture osteoporosis, allergies, drug reactions, and most 
recent menses.  
 
4.1.2.1.2 Current symptoms including those of an active systemic 
illness (e.g., fever) and bleeding or easy bruising. 
 
4.1.2.1.3 Prescription and non-prescription medication taken within 14 
days prior to entry.  
 
4.1.2.1.4 Antiretroviral drug exposure within 1 month prior to entry. 
 
4.1.2.1.5 Weight, and vital signs, including temperature, blood 
pressure, and pulse rate.   

 
 
 
4.1.2.1.6 20-question HIV Symptom Index and SF-12 Questionnaires 
 
 
4.1.2.2 
The following laboratory tests will be performed: 
 
4.1.2.2.1 Complete blood cholesterol test: Total cholesterol, LDL, HDL, 
and triglycerides.  
 
4.1.2.2.2 Metabolic Panel 
 
4.1.2.2.3 Urinalysis 
 
4.1.2.2.4 HIV RNA in blood plasma.  
 
4.1.2.2.5 Lymphocytes subset in blood (CD4+ and CD8+ T-cell 
absolute counts and percent) including CD4+ T-cell peak and 
nadir levels.  
 
4.1.2.2.6 For women of childbearing potential: Serum and urine 
pregnancy test.  
 
4.1.2.2.7 A urine drug screen will be performed.  
 
4.1.3 A four week supply of BIC/FTC/TAF will be dispensed. 
 
4.2 
On -Treatment Evaluations 
 
4.2.1 Four-Week Assessment: Subject will return at day 28 (one-week window) for 
safety assessments that will include:  
 
4.2.1.1 
Brief safety-focused clinical assessment:  
 
4.2.1.1.1 Weight, and vital signs including temperature, blood 
pressure, and pulse rate.  
 
4.2.1.1.2 A medical history assessment including symptoms and signs 
of adverse reactions.  
 
4.2.1.1.3 Study drug adherence assessment.   
 
4.2.1.2 
The following laboratory evaluations will be performed:  
 
4.2.1.2.1 Hematology: hemoglobin, hematocrit, mean corpuscular 
volume (MCV), white blood cell count, differential white blood 
cell count, and platelet count.  
 
4.2.1.2.2 Blood chemistries: electrolytes, blood urea nitrogen (BUN), 
creatinine, creatinine kinase, glucose, phosphorus, amylase, 
lactate, and calcium.  
 
4.2.1.2.3 Liver function tests: total bilirubin, AST, ALT, alkaline 
phosphatase, and albumin.  

 
 
 
4.2.1.2.4 Coagulation: prothrombin time, international normalized ratio, 
partial thromboplastic time.  
 
4.2.1.2.5 Estimated glomerular filtration rate (eGFR)  
 
4.2.1.2.6 Complete blood cholesterol test: Total cholesterol, LDL, HSL, 
and triglycerides.  
 
4.2.1.2.7 For women of childbearing potential: urine pregnancy tests.  
 
4.2.1.2.8 HIV RNA in blood plasma. 
 
4.2.1.2.9 Lymphocytes subset in blood (CD4+ and CD8+ T-cell 
absolute counts and percent) including CD4+ T-cell peak and 
nadir levels.  
 
4.2.1.3 
Drug dispensing: four additional weeks of study drug will be 
dispensed from the research pharmacy.  
 
4.2.2 Events Between Week 4 and Week 24 Visits 
 
4.2.2.1 
The study coordinator will inquire about signs or symptoms of 
adverse effects as well as medication adherence at the drug 
dispensing visits on week 8 and week 16 if subject is willing. Results 
will be recorded on CRF. If any symptoms are reported, the subject 
will be evaluated by the study nurse and investigator (see Section 
6.6).  
 
4.2.2.2 
Drug dispensing: Four weeks of study drug will be dispensed at 
Weeks 8 and 12.  
 
 
4.2.3 Week 24 Assessments  
 
4.2.3.1 
A complete medical history and physical examination will be 
performed:  
 
4.2.3.1.1 Prior diagnoses including liver disease, renal disease, 
fracture, osteoporosis, allergies, drug reactions, and most 
recent menses.  
 
4.2.3.1.2 Current symptoms including those of an active systemic 
illness (e.g., fever) and bleeding or easy bruising.  
 
4.2.3.1.3 Height, weight and vital signs, including temperature, blood 
pressure, and pulse rate.  
 
4.2.3.2 
20-question HIV Symptom Index and SF-12 Questionnaire.  
 
 
4.2.3.3 
The following laboratory tests will be performed: 
 

 
 
4.2.3.3.1 Hematology: hemoglobin, hematocrit, mean corpuscular 
volume (MCV), white blood cell count, differential white blood 
cell count, and platelet count. 
 
4.2.3.3.2 Blood chemistries: electrolytes, blood urea nitrogen (BUN), 
creatinine, creatinine kinase, glucose, phosphorus, amylase, 
lactate and calcium. 
 
4.2.3.3.3 Liver function tests: total bilirubin, AST, ALT, alkaline 
phosphatase, and albumin. 
 
4.2.3.3.4 Coagulation: prothrombin time, international normalized ratio, 
partial thromboplastin time. 
 
4.2.3.3.5 Complete blood cholesterol test: Total cholesterol, LDL, HSL, 
and triglycerides.  
 
4.2.3.3.6 Urinalysis, including urine glucose and protein. A Urine drug 
screen will also be performed. 
 
4.2.3.3.7 Estimated glomerular filtration rate (eGFR). 
 
4.2.3.3.8 For women of childbearing potential: Serum or urine 
pregnancy test. 
 
4.2.3.3.9 HIV RNA in blood plasma. 
 
4.2.3.3.10 Lymphocytes subset in blood (CD4+ and CD8+ T-cell 
absolute counts and percent) including CD4+ T-cell peak and 
nadir levels.  
 
4.2.3.4 
Subjects will be strongly encouraged to have an appointment with a 
primary care provider scheduled within a week prior to the final study 
visit to obtain a prescription and allow for clinical dispensing of 
continuing antiretroviral therapy. 
 
 
 
4.3 
Premature Discontinuation  
 
Subjects who prematurely discontinue study treatment will undergo an assessment 
similar to the one detailed for Week 24 with the following exceptions.  
 
4.3.1 Following up with a primary care provider will be discussed with the study 
subject.  
 
4.4 
Off-Drug Requirements  
 
Additional safety monitoring and reporting of Serious Adverse Events (SAEs) continues 
to be required upon completion or discontinuation of study treatment regardless of 
whether a protocol follow-up period is scheduled to occur. Adverse experiences 
occurring during the immediate 8-week period after the last dose of study treatment 
which meet SAE Reporting Requirements must be reported to the sponsor and the 

 
 
Institutional Review Board (IRB). If the study subject discontinues study treatment, 
after 8 weeks OFF study treatment, there are 4 types of events which must be reported 
to the sponsor and the IRB if the relationship to the study treatment is assessed by the 
site physician as definitely, possibly, or unable to judge: DEATHS, NEW ONSET 
CANCERS, CONGENITAL ANOMALIES, PERMANENT DISABILITIES. The study 
nurse will call the study subject eight weeks after the last study visit to determine if an 
SAE has occurred. 
 
5.0 
DATA COLLECTION AND MONITORING AND ADVERSE EVENTS REPORTING  
 
5.1 
Records to Be Kept 
 
Case report forms (CRF) will be provided for each subject. Subjects must not be 
identified by name on any study documents. Subjects will be identified by the Patient 
Identification Number (PID) and Study Identification Number (SID). 
 
All data on the CRF must be legibly recorded in black ink or typed. A correction should 
be made by striking through the incorrect entry with a single line and entering the 
correct information adjacent to it. The correction must be initialed and dated by the 
investigator or a designated qualified individual. Any requested information that is not 
obtained as specified in the protocol should have an explanation noted on the CRF as 
to why the required information was not obtained.  
 
5.2 
Monitoring  
 
5.2.1 The investigators will review the research records for accuracy, completeness, 
and legibility. The investigators will also regularly inspect regulatory files to 
ensure that regulatory requirements are being followed.  
 
5.2.2 The investigator will make study documents (e.g., consent forms, drug 
distribution forms, and case report forms) and pertinent hospital or clinic 
records readily available for inspection by the FDA for confirmation of the study 
data.  
 
5.3 
Serious Adverse Events (SAE) Reporting  
 
SAE will be documented on the SAE Reporting Form and submitted to the sponsor and 
the IRB within 24 hours of the investigator becoming aware of the event.  
 
Stopping Guidelines 
BIC/FTC/TAF has recently received US Food and Drug Administration approval. The 
safety in this small, investigator-initiated study is expected to reflect those in larger 
phase II and phase III clinical trials. In the event that an unexpected and serious safety 
signal emerges, such as more than 33% of subject having SAEs requiring treatment 
discontinuation, the investigators will strongly consider temporarily suspending or 
prematurely ending the trial.  If the participant is discontinued because of SAE, the end 
study laboratory tests will be included as a measure of safety. 
 
 
6.0 
STUDY TREATMENT  
 
6.1 
Drug Regimens, Administration, and Duration  
  

 
 
   Days 1-28: Give BIC/FTC/TAF (50 mg BIC, po q day).  
   Day 28: Assess therapy adherence.  
   Day 29-168: Continue BIC/FTC/TAF (50 mg BIC, po q day).   
 
 
 
   Day 168: Assess health related quality of life and therapy adherence.  
 
BIC/FTC/TAF (50 mg BIC, po q day) can be administered as a single dose with 
or without food.  
 
 
6.2 
Drug Formulations 
 
BIKTARVY tablets are purplish brown, capsule-shaped, and film-coated with “GSI” 
debossed on one side and “9883” on the other side. Each bottle contains 30 tablets 
(NDC 61958-2501-1), a silica gel desiccant, polyester coil, and is closed with a 
childresistant closure. Each BIKTARVY tablet contains 50 mg of bictegravir (BIC), 200 
mg of emtricitabine (FTC), and 25 mg of tenofovir alafenamide (TAF).  
Store below 30 °C (86 °F).  
• Keep container tightly closed.  
• Dispense only in original container.   
 
6.3 
Drug Supply, Distribution, and Pharmacy  
 
6.3.1 Dispensing and monitoring drug-taking behavior 
 
Subjects will be asked to bring medication bottles with any remaining 
medication to each visit. Adherence will be assessed through pill count and 
documented by project staff on appropriate CRFs.  
 
6.3.2 Study supply acquisition  
 
The study treatment will be supplied by Gilead Sciences to the study site and 
will then be dispensed by the research pharmacy.  
 
6.3.3 Accountability  
 
The study pharmacist will maintain complete records of all study medications 
received and subsequently dispensed in an accountability log.   
 
All unused study medication will be returned to the study pharmacy and 
discarded following standard operating procedure.  
 
6.4 
Concomitant Medications  
 
6.4.1 Precautions  
 
Bictegravir has been recently approved by the FDA. A comprehensive list on 
precautionary medications has become available in the package insert15. 
Pharmacokinetic studies have shown bictegravir is metabolized primarily by 
CYP3A4 and UGT1A1. BIC/FTC/TAF should NOT be recommended with 
strong CYP3A4 and UGT1A1 inducers such as rifampin that can significantly 
decrease bictegravir plasma concentration. Co-administration of BIC/FTC/TAF 
should also be NOT recommended with potent inhibitors of both CYP3A4 and 
UGT1A1 that can result in elevated bictegravir plasma concentrations. 

 
 
 
6.4.2 Contraindications  
 
BIKTARVY is contraindicated to be co-administered with:  dofetilide due to 
the potential for increased dofetilide plasma concentrations and associated 
serious and/or life-threatening events;  rifampin due to decreased BIC plasma 
concentrations, which may result in the loss of therapeutic effect and 
development of resistance to BIKTARVY.  Specific case-by-case exemptions 
may be considered by the study investigators.  
 
6.5 
Management of Selected Toxicities   
 
6.5.1 New Onset or Worsening Renal Impairment  
 
Renal impairment, including acute renal failure and Fanconi syndrome, has 
been reported with prodrugs of tenofovir. A tenofovir prodrug, tenofovir 
alafenamide is a component of BIC/FTC/TAF. If renal impairment occurs as 
indicated by a decrease of estimated creatinine clearance below 30 mL/min, 
study treatment will be discontinued and subjects will complete the evaluations 
listed in Section 4.2.  
 
6.5.2 Lactic Acidosis/ Severe Hepatomegaly  
 
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, 
have been reported with the use of nucleoside reverse transcriptase inhibitors 
(NRTI). Treatment with BIC/FTC/TAF should be suspended in any subject who 
develops clinical or laboratory findings suggestive of lactic acidosis or 
pronounced hepatotoxicity. 
 
6.5.3 Fat Redistribution and Immune Reconstitution Syndrome  
 
Redistribution/accumulation of body fat and immune reconstitution syndrome 
have been reported in patients treated with antiretroviral therapy such as NRTI 
and possibly INSTI, which may necessitate further evaluation and treatments.  
 
Any grade 3 or higher symptoms or laboratory abnormalities will result in 
termination of the subject from the study (see Section 4.2 for post-treatment 
evaluations).  
 
6.6 
Criteria for Treatment Discontinuation  
 
6.6.1 The Subject or legal guardian refuses further treatment and/or follow-up 
evaluations.  
 
6.6.2 The investigator determines that further participation would be detrimental to 
the subject’s health.  
 
6.6.3 The subject fails to comply with the study requirements so as to cause harm to 
self or seriously interfere with the validity of the study results.  
 
6.6.4 The subject requires treatment with medications that are disallowed while on 
this study (Section 6.4.2).  
 

 
 
6.6.5 Drug toxicities as defined in Section 6.5.  
 
6.6.6 Pregnancy.  
 
 
7.0 
STATISTICAL CONSIDERATIONS 
 
7.1 
General Design Issues  
 
The first objective of this study is to evaluate PDDI when switched from GenvoyaTM or 
StribildTM to bictegravir/F/TAF. This will be accomplished by selecting subjects who are 
currently on GenvoyaTM or StribildTM. More than one provider prescribing medications 
can cause discrepancy in polypharmacy related data collection. In this study, all 
prescribed medication as well as non-prescription medication in each subject’s regimen 
will be collected prior to (4-8 weeks) and after switch and analyzed. For the other first 
and secondary objectives, which is to evaluate health related quality of life and 
adherence, we will consider response biases in these measures.  We will include all 
participants >50 years old for overall analysis followed by post hoc analyses of 
medication type and number related to the changes in the outcomes. 
 
7.1.1 Endpoints  
 
7.1.1.1 
Primary endpoints 
 
 
7.1.1.1.1 Probability of PDDI particularly with cobicistat and concurrent 
medications will be assessed throughout the study.  
 
7.1.1.1.2 Health related quality of life assessments at baseline, week 
12 and week 24. 
 
 
7.1.1.2 
Secondary endpoints  
 
 
7.1.1.2.1 Adherence assessment at baseline, week 4, week 8, week 
12 and week 24.  
 
7.1.1.2.2 Lipid panel, blood pressure and blood glucose levels at 
baseline, week 12 and week 24. 
 
7.2 
Sample Size and Accrual  
 
Sample size of 160, consisting of 80 subjects who are engaged in polypharmacy (⩾5 
meds) and 80 subjects who are not, will be sufficient for the primary objective to 
determine the impact of polypharmacy and the reduced probability of PDDI on the 
quality of life.  Among 160 subjects, 80 (50%) will be the elderly (⩾50 years old) evenly 
distributed in the two groups.  The impact of aging will be evaluated in two ways: (1) 
age as a continuous variable and (2) old (⩾50 years old) vs. young (<50 years old).  
The basic study design proposed is a parallel, open-label approach that will permit 
adequate power to determine the effect of polypharmacy and reduced PDDI, mainly 
related to cardiovascular and neurological medications, on the quality of life after the 
regimen switch.  Our power analysis indicates that a sample size of 80 in each group 

 
 
(polypharmacy vs. non-polypharmacy) will be sufficient for the comparisons we need to 
make. Previous studies on polypharmacy in HIV+ elderly (⩾50) indicate that the 
incidence of polypharmacy will be approximately 40-50% (16-18). We have also 
assumed that a 15-20% difference or greater in quality of life or levels of well-being 
would be of clinical importance (19, 20).  The component of this study comprising the 
comparative evaluation of quality of life and PDDI in polypharmacy and non-
polypharmacy patients is a parallel design. A sample size of 160 (80 in each group) will 
be needed to detect a 20% difference at a power of between 0.75 and 0.80. This will 
accommodate the relatively high incidence of polypharmacy and PDDI among the 
elderly living with HIV and permit an analysis for the effect of switch from GenvoyaTM or 
StribildTM to bictegravir on quality of life. 
 
Any subject who prematurely discontinues study participation prior to completing at 
least one on-treatment assessment including health related quality of life questioners 
and data collection will be replaced by another subject.  The alternative approach is to 
allow subjects currently receiving HIV care from the Erie County Medical Center to 
participate in the study. 
 
7.3 
Monitoring and Analysis  
 
The safety and tolerability of the study medications will also be monitored closely by 
the protocol team comprising an HIV pharmacist with experience in clinical trials, an 
expert in HIV clinical trials, and an expert in clinical research. Reports and responses 
will be prepared by the protocol team.  
 
 
8.0 
HUMAN SUBJECTS  
 
8.1 
Institutional Review Board (IRB) Review and Informed Consent  
 
This protocol and the informed consent document and any subsequent modifications 
will be reviewed and approved by the Institutional Review Board at each participating 
institution. Written informed consent will be obtained from the subject. Subjects who 
are unable to provide consent due to neurocognitive impairment or other causes will 
not be enrolled. The informed consent will describe the purpose of the study, the 
procedures to be followed, and the risks and benefits of participation. A copy of the 
consent form will be given to the subject (or legal guardian). 
 
 
8.2 
Data Storage and Subject Confidentiality  
 
All laboratory specimens, evaluation forms, reports, and other records will be identified 
by a coded number only to maintain subject confidentiality. All records will be kept in a 
locked file cabinet. All computer entry and networking programs will be done with 
coded numbers only. Clinical information will not be released without written 
permission of the subject, except as necessary for monitoring by the FDA or the 
pharmaceutical sponsor. 
 
8.3 
Costs to the Subjects  
 
All study costs will be covered by the study sponsor as specified in the existing 
contract. There will be no costs to the subject associated with participation in the study. 
 

 
 
8.4 
Compensation for Participation  
 
Subjects will be reimbursed $10 for phlebotomy (no more than once per visit) and $10 
for completion of forms. Subjects who completes all assessments will be compensated 
a total of $70. By visit, subjects who complete all assessments will receive $10 at 
screening, $20 at entry at weeks 2 and 24. 
 
8.5 
Study Discontinuation  
 
The study may be discontinued at any time by the investigators, the pharmaceutical 
sponsors, or the FDA. Discontinuation by the pharmaceutical sponsor must follow 
guidelines set forth in the contract with the award recipient institution, the University at 
Buffalo. 
 
9.0 
PUBLICATION OF RESEARCH FINDINGS  
 
Any presentation, abstract, or manuscript will be made available for review by the 
pharmaceutical sponsors prior to submission. The investigators will retain the right of final 
revision of all presentations, abstracts, and manuscripts. 
 
 
10.0 BIOHAZARD CONTAINMENT  
 
As the transmission of blood-borne pathogens can occur through contact with contaminated 
needles, blood, and blood products, appropriate blood and secretion precautions will be 
employed by all personnel in the drawing of blood and shipping and handling of all specimens 
for this study, as currently recommended by the Centers for Disease Control. 
 
All infectious specimens will be sent using the ISS-1 SAF-T- PAK mandated by the 
International Air Transport Association Dangerous Goods Regulations-Packing Instruction 
602. Please refer to individual carrier guidelines (e.g., FedEx, Airborne) for specific 
instructions. 
 
 
 
 

 
 
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