SymITA: Switch to DRV/COB/FTC/TAF From Integrase Containing Regimens to Evaluate Changes in Tolerability/Adherence
Phase: PHASE4
Conditions: Human Immunodeficiency Virus
Sponsor: Midland Research Group, Inc.

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
CONFIDENTIAL 
Page 1 of 38 
SymITA:  
Switch to DRV/COB/FTC/TAF from Integrase 
containing regimens to evaluate changes in 
Tolerability/Adherence  
 
 
Protocol Number: 
TMC114FDZHTX4005 
 
Version:  
 
1.1 
 
Date:   
 
October 10, 2019 
 
IRB Approval Date: 
December 17, 2019 
 
Sponsor:  
 
Midland Research Group 
 
 
 
1421 East Oakland Park BLVD, Suite 200 
 
 
 
Oakland Park, FL 33334 
 
 
 
954-565-0875 
 
 
 
 
Principal Investigator: Erik Lowman, DO 
 
Sub-Investigators:  
Noah Lee, DO 
 
 
 
Sarah Long, DNP, FNP-BC 
 
Study Contact:  
Anthony Ciesielski, MD 
 
 
 
1421 East Oakland Park BLVD, Suite 200 
 
 
 
Oakland Park, FL 33334 
 
 
 
954-375-1275 
 
 
 
TonyC@midlandresearchgroup.com 
 
Janssen Scientific Affairs, LLC is providing funding and study drug Symtuza 
 
Reviewing Investigational Review Board (IRB): 
CIRBI/Advarra 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 USA 
Main Telephone Number: (410) 884-2900 
CIRBI Help Desk Telephone Number: 1 (866) 992-4724 
Email: cirbi@advarra.com 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
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Table of Contents 
1. 
Introduction        
 
 
 
 
 
 
 
4                                                           
2. 
Rationale for the Study 
 
 
 
 
 
 
 
4 
 
3. 
Study Objectives  
 
 
 
 
 
 
 
5 
4. 
Study Endpoints  
 
 
 
 
 
 
 
5 
5. 
Study Drug 
 
 
 
 
 
 
 
 
6 
6. 
Study Design 
 
 
 
 
 
 
 
 
7 
6.1. 
Part 1 
 
 
 
 
 
 
 
 
7 
6.1.1. 
Methodology  
 
 
 
 
 
 
7 
6.1.2. 
Sample  
 
 
 
 
 
 
7 
6.1.3. 
Eligibility criteria  
 
 
 
 
 
7 
6.1.4. 
Study Procedure                                                                                  
7 
6.2. 
Part 2 
 
 
 
 
 
 
 
 
8 
6.2.1. 
Methodology  
 
 
 
 
 
 
8 
6.2.2. 
Sample  
 
 
 
 
 
 
8 
6.2.3. 
Eligibility Criteria  
 
 
 
 
 
8 
6.2.4. 
Study Procedure  
 
 
 
 
 
10 
6.2.4.1. Overview 
 
 
 
 
 
10 
6.2.4.2. Positive Screen 
 
 
 
 
 
10 
 
6.2.4.3. Screening Visit 
 
 
 
 
 
10 
6.2.4.4. Baseline Visit 
 
 
 
 
 
11 
6.2.4.5. Week 4 Visit 
 
 
 
 
 
11 
6.2.4.6. Week 14 Event 
 
 
 
 
 
11 
6.2.4.7. Week 16 Visit 
 
 
 
 
 
11 
6.2.4.8. Early discontinuation visit  
 
 
 
11 
6.2.4.9. Post Study Visit  
 
 
 
 
11 
7. 
Safety Data Collection and Reporting  
 
 
 
 
 
13 
7.1. 
See Appendix 3 (Exhibit B)  
 
 
 
 
 
13 
7.2. 
Clinical Laboratory Abnormalities as Adverse Events   
 
 
13 
7.3. 
Assessment of Adverse Events 
 
 
 
 
 
13 
7.4. 
Assessment of Causality for Study Drugs and Procedures 
 
 
13 
7.5. 
Assessment of severity 
 
 
 
 
 
 
13 
7.6. 
Toxicity Management 
 
 
 
 
 
 
13 
7.6.1. 
Additional Notes  
 
 
 
 
 
13 
7.6.2. 
Grades 1,2 Clinical Event or Laboratory Abnormality   
 
14 
7.6.3. 
Grade 3 Clinical Event or Laboratory Abnormality 
 
 
14 
7.6.4. 
Grade 4 Clinical Event or Laboratory Abnormality 
 
 
14 
7.6.5. 
ALT Flare 
 
 
 
 
 
 
14 
7.6.6. 
Management of Potential Hepatobiliary Toxicity 
 
 
15 
7.7. 
Criteria for discontinuation of study drug 
 
 
 
 
15 
7.8. 
Management of viral rebound 
 
 
 
 
 
15 
8. 
Statistical Considerations  
 
 
 
 
 
 
15 
9. 
Responsibilities  
 
 
 
 
 
 
 
19 
References 
 
 
 
 
 
 
 
 
 
21 
Appendix 1-Midland ART Adherence Survey  
 
 
 
 
 
22 
 
 
Appendix 2-Self Completed HIV Symptom Index Survey 
 
 
 
 
23 
Appendix 3-Exhibit B, Safety Data Collection and Reporting                       
 
 
24 
 
Appendix 4- Grading Scale for Severity of Adverse Events and Laboratory Abnormalities  
30 
Appendix 5- Study Procedure Schedule 
 
 
 
 
 
 
36 
Appendix 6- Contraindicated Concomitant Medications 
 
 
 
 
37 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
CONFIDENTIAL 
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Appendix 7- Positive Screen Criteria for Part 2  
 
 
 
 
 
38 
 
 
 
AE 
Adverse Event 
ART  
Anti-retroviral Therapy 
BMI  
Body Mass Index 
CBC 
Complete Blood Count 
CD4  
helper T lymphocytes positive for surface glycoprotein CD4 
CI  
confidence interval  
CMP 
Complete Metabolic Panel  
COB 
Cobicistat 
DRV 
Darunavir 
FDC  
fixed dose combination  
FTC 
Emtricitabine 
HBsAg  hepatitis B virus surface antigen serology 
HBV  
hepatitis B virus 
HCV  
hepatitis C virus 
HCV Ab Hepatitis C virus antibody  
HIV 
Human Immunodeficiency Virus-1 
HIV-SI HIV Symptom Index 
IRB  
institutional review board  
MAAS  Midland Antiviral Adherence Survey 
PII  
Personal Identifying Information 
PRO  
Patient Reported Outcome survey 
STR 
Single Tablet Regimen 
TAF 
tenofovir alafenamide 
SEA 
Serious Adverse Event 
VL  
viral load 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
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Version: 1.1 Final  17 Dec 2019 
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1. Introduction 
 
Human Immunodeficiency Virus-1 (HIV) is a life threatening and serious infection throughout the world.  
The World Health Organization estimates between 30-43 million people are living with HIV worldwide. 
The natural progression of the disease cripples the immune system, leading to unchecked infections and 
ultimately death. 
With the advent of anti-retroviral therapy, HIV transformed from a terminal infection into a manageable 
chronic disease for patients who were able to obtain medications, provided they could remain adherent 
to them.  
When single tablet regimens (STR) became available, adherence to HIV medications was made easier for 
many patients. However even years after STR became available, 38% of patients reported they do not 
maintain optimal adherence to their HIV medications1. While there are many factors that contribute to 
this problem, medication intolerance contributes to suboptimal adherence for many patients 2.  
 
2. Rationale for the Study 
 
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/COB/FTC/TAF) is a coformulated STR, is 
the only protease inhibitor based STR, and is noted for its high tolerability3. These traits have the potential 
to improve adherence in patients who have intolerance to the integrase inhibitor class. We propose a two 
part study design to evaluate if patients who have suboptimal adherence due to integrase inhibitor 
intolerance may better tolerate Symtuza and subsequently have improved adherence.  
 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
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3. Study Objectives 
3.1. Part 1 
3.1.1. Primary Objectives 
3.1.1.1. To assess degree of adherence to ART in a real world setting 
3.1.2. Secondary Objectives 
3.1.2.1. To evaluate trends and patterns in subjects who report suboptimal adherence 
3.2. Part 2 
3.2.1. Primary Objectives 
3.2.1.1. To determine potential changes in ART adherence in subjects who report suboptimal 
adherence due to side effects from integrase containing regimens switching to Symtuza. 
3.2.2. Secondary Objectives 
3.2.2.1. To evaluate the tolerability of switching from integrase containing regimen to Symtuza with 
the aid of Patient Reported Outcomes (PRO) questionnaire and number of drug discontinuation 
for any reason 
3.2.2.2. To determine the safety of switching from integrase containing regimen to Symtuza in subjects 
with HIV-1 infection as determined by the proportion of participants with virologic failure, a 
change in laboratory parameters, and change in CD4 cell count from baseline. 
3.2.2.3. To evaluate for potential weight loss when switching from integrase containing regimen to 
Symtuza 
 
 
4. Study Endpoints 
 
4.1. Part 1 
4.1.1. Primary Endpoint  
4.1.1.1. Percentage of subjects reporting suboptimal adherence 
4.1.2. Secondary Endpoint  
4.1.2.1. Percentage of subjects who report suboptimal adherence due to tolerance issues/side effects 
4.1.2.2. Percentage of subjects who report suboptimal adherence due to reasons other than 
tolerance issues/side effects 
4.2. Part 2 
4.2.1. Primary Endpoint: 
4.2.1.1. Change in adherence from baseline to 4 months, measured by adherence surveys 
4.2.2. Secondary Endpoints: 
4.2.2.1. Change at 4 months from baseline in tolerability measured by standardized patient reported 
outcome questionnaire 
4.2.2.2. Proportion of subjects that have HIV-1 RNA ≥ 50 copies/mL at baseline and at Week 16 
4.2.2.3. Proportion of subjects with significant changes at 4 months from baseline in serum 
creatinine, AST or ALT 
4.2.2.4. Change at 4 months from baseline in absolute and percentage CD4. 
4.2.2.5. Change at 4 months from baseline in absolute and percentage weight 
4.2.2.6. Number of drug discontinuation for any reason 
4.2.2.7. Compare adherence measured by adherence surveys on week 4 and Week 16 to the pill 
counts from week 4 and Week 16. 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
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5. Study Drug 
 
5.1. Formulation 
5.1.1. SYMTUZA (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide) is an FDA approved fixed-
dose combination tablet complete regimen for the treatment of HIV-1 infection in adults: • who have 
no prior antiretroviral treatment history or • who are virologically suppressed (HIV-1 RNA less than 
50 copies per mL) on a stable antiretroviral regimen for at least 6 months and have no known 
substitutions associated with resistance to darunavir or tenofovir.. • Darunavir is an inhibitor of the 
HIV-1 protease. • Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of 
the CYP3A family. • Emtricitabine, a synthetic nucleoside analog of cytidine, is an HIV nucleoside 
analog reverse transcriptase inhibitor (HIV NRTI). • Tenofovir alafenamide, an HIV NRTI, is converted 
in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5ʹ-
monophosphate. SYMTUZA tablets are for oral administration. Each tablet contains darunavir 
ethanolate equivalent to 800 mg of darunavir, 150 mg of cobicistat, 200 mg of emtricitabine, and 
11.2 mg of tenofovir alafenamide fumarate equivalent to 10 mg of tenofovir alafenamide. The tablets 
include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, 
magnesium stearate, and microcrystalline cellulose. The tablets are film-coated with a coating 
material containing polyethylene glycol (macrogol), polyvinyl alcohol (partially hydrolyzed), talc, 
titanium dioxide, and yellow ferric oxide. 
5.1.2. Symtuza will be considered investigational in this study for those patients who are not virally 
suppressed at study entry. 
 
5.2. Packaging and Labeling/Storage and Handling 
5.2.1. SYMTUZA (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets are supplied as 
yellow to yellowish-brown, capsule-shaped, film-coated tablets debossed with “8121” on one side 
and “JG” on the other side. SYMTUZA is packaged in bottles of 30 tablets (NDC 59676-800-30), with 
a silica gel desiccant and child-resistant closure.  
5.2.2. Study drug will be stored at 20°C-25°C (between 68°F-77°F); with excursions permitted to 15°C-30°C 
(59°F-86°F). • Dispensed in the original container. Container will be tightly closed with desiccant 
inside to protect from moisture. 
 
5.3. Dosage and Administration 
5.3.1. Study drug will be dosed as one tablet taken orally once daily with food in adults. For subjects who 
are unable to swallow the whole tablet, it may be split into two pieces using a tablet-cutter, and the 
entire dose should be consumed immediately after splitting. 
 
5.4. Concomitant Medications 
5.4.1.  Contraindicated medications: 
5.4.1.1. SYMTUZA® and the following drugs due to the potential for serious and/or life-threatening 
events or loss of therapeutic effect: alfuzosin, carbamazepine, cisapride, colchicine (in patients 
with renal and/or hepatic impairment), dronedarone, elbasvir/grazoprevir, ergot derivatives 
(such as: dihydroergotamine, ergotamine, methylergonovine), ivabradine, lomitapide, 
lovastatin, lurasidone, oral midazolam, naloxegol, phenobarbital, phenytoin, pimozide, 
ranolazine, rifampin, St. John’s wort (Hypericum perforatum), sildenafil for pulmonary arterial 
hypertension, simvastatin, and triazolam. 
5.4.2. Not recommended agents: 
5.4.2.1. Rivaroxaban, 
esclicabazepine, 
oxcarbazepine, 
voriconazole, 
rifapentine, 
rifabutin, 
betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, 
mometasone, triamcinolone, glecaprevir/pibrentasvir, simeprevir, everoliumus, irinotecan, 
salmeterol, avanafil, ticagrelor. 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
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5.5. Accountability for Study Drug 
5.5.1. Subjects will be instructed to bring all study medication in the original container at each clinic visit for 
drug accountability. The Investigator will be responsible for maintaining accurate records for all study 
drug bottles dispensed and tablets returned. Study medication supplies, including partially used or 
empty bottles, must be accounted for by the investigator prior to destruction of return. 
5.5.2. The Investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. This included acknowledgement of receipt of each shipment of study drug (quality and 
condition). All used and unused study drug dispensed to subjects must be returned to the site. 
 
5.5.3. Study Drug accountability records will include: 
5.5.3.1. Date received and quantity of IMP kits 
5.5.3.2. Date, subject number, subject initials, the IMP kit number dispensed 
5.5.3.3. Date, quantity of used and unused IMP returned, along with the initials of the person 
recording the information. 
 
5.6. Product Return or Disposal 
5.6.1. Study drug return or disposal will be performed on site.  
 
6. Study Design 
 
6.1. 
Part 1 
 
6.1.1. Methodology  
6.1.1.1. Part I of the study is a Cohort Survey of HIV+ outpatient clinic patients currently receiving ART 
to assess medication adherence and tolerability. 
 
6.1.2. Sample 
6.1.2.1. Convenience sample of patients being seen in a single clinical site 
6.1.2.2. Duration will be until enrollment of Part II has been completed 
 
6.1.3. Eligibility criteria 
6.1.3.1. Inclusion Criteria: 
6.1.3.1.1. ≥ 18 years of age 
6.1.3.1.2. HIV positive receiving ART of any type 
 
6.1.3.2. Exclusion criteria 
6.1.3.2.1. Inability to read/respond to questions written in English OR Spanish 
 
6.1.4. Study Procedure 
6.1.4.1. During patient triage, all patients who are HIV positive and currently prescribed anti-viral 
therapy will be offered participation in completing the Midland ART Adherence Survey (MAAS, 
Appendix 1). They will be provided a paper copy of the Study consent and the survey with a 
clipboard and a pen and allowed to self-complete it during the triage process. If they opt-in to 
the survey, they will turn in the completed surveys to staff members who will (1) determine if 
patient is eligible for Part II of study and (2) share the results with the provider, if subjects 
indicate they would like them shared. For those who opt out, no demographic data will be 
collected. 

Symtuza (DRV/COB/FTC/TAF) 
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Version: 1.1 Final  17 Dec 2019 
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6.1.4.2. Survey sheets will not contain any Personal Identifying Information (PII). The results of the 
survey will be entered into a spreadsheet and analyzed at the completion of the enrollment 
period. 
6.1.4.3. Subjects will be offered enrollment in Part 1 until target enrollment in part 2 has been 
completed or until subject sample population has been offered participation, whichever comes 
first. 
 
6.2. 
Part 2 
 
6.2.1. Methodology  
6.2.1.1. Part 2 of the study is a prospective cohort analysis of change in adherence, tolerability and 
safety of subjects who reports poor adherence to ART due to intolerance/side effects from 
integrase inhibitor containing regimens when they are switched to DRV/COB/FTC/TAF and 
monitored for 4 months. 
 
6.2.2. Sample 
6.2.2.1. All subjects who meet pre-determined criteria from MAAS and meet other eligibility 
requirements will be offered enrollment into Part II of the study, the target enrollment is 30. 
 
6.2.3. Eligibility Criteria 
 
6.2.3.1. Inclusion Criteria 
6.2.3.1.1. Meets inclusion criteria of part I of study 
6.2.3.1.1.1. Currently on an integrase containing regimen AND 
6.2.3.1.1.2. Reports non-adherent due to medication intolerance, defined by pre-determined 
criteria from Adherence Survey: [indicate a side effect to question 11 OR “yes” to 
questions 3 OR 7] AND [indicate missing more than 2 doses per month on 
question 8 OR 9 OR 10]) 
6.2.3.1.2. GFR≥30mL/min 
6.2.3.1.3. AST/ALT ≤ 3 times upper limit of normal 
6.2.3.1.4. Total bilirubin of ≤1.5 mg/dL 
 
6.2.3.2. Exclusion Criteria 
6.2.3.2.1. Known resistance to darunavir or tenofovir 
6.2.3.2.2. Known intolerance to Symtuza or its components 
6.2.3.2.3. Current pregnancy 
6.2.3.2.4. Requires continued use of any of the agents in table 6.2.3.2.4 
6.2.3.2.5. Cirrhosis, regardless of compensation status 
6.2.3.2.6. Active, serious infections within 30 days of baseline 
6.2.3.2.7. History of malignancy within 5 years of baseline, except cutaneous Kaposi’s sarcoma, 
basal cell or resected non-invasive cutaneous squamous cell carcinoma 
6.2.3.2.8. Life expectancy of less than a year 
6.2.3.2.9. Participation in any other investigation study 30 days prior to enrollment 
 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
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Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
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Table 6.2.3.2.4 Contraindicated/not recommended Concomitant Medications 
Alpha 1-Adrenoreceptor Antagonist 
alfuzosin  
Antiarrhythmics/Antianginals  
amiodarone, dronedarone, ivabradine, lidocaine 
(systemic)  
Anti-coagulants  
apixaban,rivaroxaban,  
Anti-convulsants  
carbamezepine, phenobarbital, phenytoin, 
oxcarbazepine, esclicabazepine  
Anti-gout  
colchicine (in patients with renal and/or hepatic 
impairment)  
Antimycobacterial  
Rifampin,  rifapentine, rifabutin 
Ergot Derivatives 
Such as: dihydroergotamine, ergonovine, 
ergotamine  
Hepatitis C Virus Direct-Acting Antivirals  
elbasvir/grazoprevir , glecaprevir/pibrentasvir, 
simeprevir 
Herbal Products St. 
John’s wort (Hypericum perforatum)  
HMG-CoA Reductase Inhibitors 
lovastatin, simvastatin  
Other Lipid Modifying Agents 
lomitapide  
Inhaled Beta Agonist  
salmeterol  
Neuroleptics 
lurasidone, pimozide 
Opioid Antagonist  
naloxegol  
PDE-5 Inhibitor  
sildenafil (for treatment of pulmonary arterial 
hypertension), avanafil  
Platelet Aggregation Inhibitor  
ticagrelor  
Sedatives/Hypnotics  
triazolam 
Antiplatelet 
ticagrelor 
antineoplastic 
Everoliumus, irinotecan 
antifungals 
voriconazole 
Steroids 
betamethasone, budesonide, ciclesonide, 
dexamethasone, fluticasone, 
methylprednisolone, mometasone, 
triamcinolone 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Midland Research Group, Inc 
Version: 1.1 Final  17 Dec 2019 
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6.2.4. Study Procedure 
 
6.2.4.1. Overview 
6.2.4.1.1. Subjects who are referred for screening from Part I who meet other eligibility criteria 
(see table 6.2.4.2.1) will be offered enrollment in Part 2. Those who provide consent will 
complete HIV Symptom Index (HIV-SI), a validated Patient Reported Outcome survey to 
assess side effects/quality of life, undergo physical and laboratory examinations, and ART 
will be switched to DRV/COB/FTC/TAF (Symtuza). For subjects who were not suppressed 
at their last lab evaluation, an HIV genotype will be performed prior to enrollment. 
Subjects who do not provide consent to enroll in the study will be referred back to their 
provider to address issues with tolerance and adherence. 
6.2.4.1.2. Subjects will be followed for 16 weeks. During that period, they will be brought back for 
evaluation at the 4th and 16th week. At those evaluations, they will again complete the 
PRO and adherence surveys to assess tolerability and adherence. At the evaluations, they 
will also be monitored for safety and effectiveness via physical exams and laboratory 
studies. See Table 6.2.4.1.2 
6.2.4.1.2.1. Labs at each visit: Complete Blood Count, Complete Metabolic Panel, Urinalysis, 
CD4 panel, HIV1 Quantitative viral load. If subject is of childbearing potential, urine 
pregnancy will be performed.  
6.2.4.1.2.1.1. Special situations: If HIV viral load is >200 prior to baseline and not 
accompanied by recent genotype, a genotype will be performed.  
6.2.4.1.3. Interim analysis will be performed when all subjects have completed 1 month evaluation 
or when 10 subjects have completed 4 month evaluation, whichever comes first. 
 
 
6.2.4.2. Positive Screen 
6.2.4.2.1. Subjects who screen positive from adherence survey defined as: (1)( indicate “yes” to 
questions 3 OR 7; or indicate a side effect to question 11) AND (2) (indicate missing more 
than 2 doses per month on question 8 OR 9 OR 10) will be offered enrollment in Part II.  
 
Table 6.2.4.2.1 Positive Screen for Part 2 
Positive screen for Part II one positive response in both columns: 
One from below 
One from below 
Question 3 = “Yes” 
Question 8 =  not “always” or “almost always” 
Question 7 = “Yes” 
Question 9 = greater than 2 
Question 11 = “Side effect(s)” or named side effect 
Question 10 = greater than 2 
 
6.2.4.3. Screening Visit 
6.2.4.3.1. At screening, written informed consent will be obtained; medical history of HIV-1 
disease, current medications and medication history will be documented, any available 
HIV-1 resistance assays and hepatitis B immunity/viral loads will be documented, vitals 
(blood pressure, pulse, temperature, height and weight) from triage will be documented, 
physical exam will be performed.  
6.2.4.3.2. After screening is performed, subjects will be allowed to either initiate baseline 
assessment or return within 45 days to do so. 
 

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6.2.4.4. Baseline Visit 
6.2.4.4.1. If required labs have been performed within 30 days baseline may be performed same 
day and self-completed HIV Symptom Index (HIV-SI, Appendix 2) survey will be 
completed, baseline labs will be drawn and patient will be given 30 day supply of study 
drug.   
6.2.4.4.2. If baseline is not done same day: vitals will be taken prior to HIV-SI survey being 
completed. Then updated history and symptom based physical will be performed and 
baseline labs will be drawn. Patient will be given 30 day supply of study drug; first dose 
will be taken in office. 
 
6.2.4.5. Week 4 Visit 
6.2.4.5.1. At 4 week visit, vitals will be taken, pill count will be performed, MAAS and HIV-SI surveys 
completed. Followed by history, symptom based physical, and laboratory exam. Patient 
will be given 90-day supply of study drug. 
 
6.2.4.6. Week 14 Event 
6.2.4.6.1. A script for commercial study drug will be sent to the patient’s pharmacy of choice 
approximately 2 weeks prior to week 16 visit to ensure uninterrupted ART for the 
patient. Staff will confirm with patient that medication will be available to them via 
pharmacy prior to 16 week visit.  
 
6.2.4.7. Week 16 Visit 
6.2.4.7.1. At 16 week visit, subjects will have vitals taken, pill count will be performed; both the 
MAAS and HIV-SI will be completed, followed by history, symptom based physical, and 
laboratory exam.  Pill count will be taken from bottle dispensed at baseline visit. Staff 
will confirm with patient that they have the commercial medication .  
 
6.2.4.8. Early Discontinuation Visit 
6.2.4.8.1. If the subject discontinues the study drug prior to the Week 16 Visit, the subject will be 
asked to return to the clinic within 10 days of stopping study drug for the Early Study 
Drug Discontinuation Visit. Every attempt should be made to keep the subject in the 
study and continue to perform the required follow ups and procedures through to the 
Week 16 Visit. If this is not acceptable to the subject or investigator, the subject may be 
withdrawn from the study. In the event that the subject is not kept in the study, physical 
and laboratory exam, as well as the MAAS and HIV-SI should be performed unless the 
subject does not consent to them.  
 
6.2.4.9. Post Study Visit 
6.2.4.9.1. If any significant abnormality is detected either at 4 month end of study visit or early 
discontinuation visit, a repeat exam and laboratories will be performed approximately 
30 days following (or sooner, if PI believes to be clinically indicated) to ensure their 
resolution, unless at the determination of the PI they are deemed not related to the 
study drug. 
 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
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Table 6.2.4.1.2: Overview of Study Procedures 
 
Procedures 
Screening 
and/or 
Baseline 
Combined 
Visit 
Screening 
(if not same 
day as 
screen) 
Baseline 
(if not same 
day as 
screen) 
Week 4 
Week 
14 
Event 
Week 16 
Early 
Discontinuation 
Vitals 
X 
X 
X 
X 
 
X 
X 
MAAS  
X 
X 
 
X 
 
X 
X 
HIV-SI 
X 
 
X 
X 
 
X 
X 
History and 
Physical 
X 
X 
 
 
 
 
 
History and 
Symptom 
based 
physical 
 
 
X 
X 
 
X 
X 
Complete 
Blood Count 
X 
 
X 
X 
 
X 
X 
CD4 panel 
X 
 
X 
X 
 
X 
X 
Complete 
Metabolic 
Panel 
X 
 
X 
X 
 
X 
X 
HIV-1 
Quantitative 
viral load 
X 
 
X 
X 
 
X 
X 
Urinalysis 
X 
 
X 
X 
 
X 
X 
Study Drug 
Dispensation 
 
 
X 
X 
 
 
 
Treatment 
Adherence 
and 
Accountability 
 
 
 
X 
 
X 
 
Commercial 
Script sent to 
Patient’s 
Pharmacy 
 
 
 
 
X 
 
 
HIV Genotype 
if viral load 
>200 
copies/mL at 
last check 
 
if viral load 
>200 
copies/mL 
at last check 
if viral load 
>200 
copies/mL 
at last check 
 
if viral load 
>200 
copies/mL at 
last check 
if viral load >200 
copies/mL at last 
check 
Urine 
pregnancy 
if 
indicated 
 
if 
indicated 
if 
indicated 
 
if 
indicated 
if indicated 
Hepatitis B 
viral load 
if 
indicated 
 
if 
indicated 
if 
indicated 
 
if 
indicated 
if indicated 
 
 

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7. Safety Data Collection and Reporting  
7.1. See Appendix 3 (Exhibit B, Safety and Data Reporting) 
 
7.2. Clinical Laboratory Abnormalities as Adverse Events  
7.2.1.1. Laboratory abnormalities (e.g., clinical chemistry, hematology, and urinalysis) that require 
medical or surgical intervention or lead to study drug interruption, modification or 
discontinuation must be recorded as an AE or SAE. In addition, laboratory or other abnormal 
assessments (e.g., EKG, x-rays, and vital signs) that are associated with signs and/or symptoms 
must be recorded as an AE or SAE if they meet the definition. If the laboratory abnormality is 
part of a syndrome, record the syndrome or diagnosis, not the laboratory result (i.e. “anemia,” 
not “decreased hemoglobin”). 
7.3. Assessment of Adverse Events 
7.3.1.1. The investigator or qualified sub-investigator is responsible for assessing AEs and SAEs for 
causality and severity as well as for final review and confirmation of accuracy of event 
information and assessments. 
 
 
7.4. Assessment of Causality for Study Drugs and Procedures 
7.4.1.1. The investigator or qualified sub-investigator is responsible for assessing the relationship to the 
study drug using clinical judgement and the following considerations: 
7.4.1.1.1. No: Evidence exists that the adverse event has an etiology other than the study drug. For 
SAEs, an alternative causality must be provided (e.g., preexisting condition, underlying 
disease, intercurrent illness, or concomitant medication). 
7.4.1.1.2. Yes: There is reasonable possibility that the event may have been caused by the study 
drug.  
7.4.1.2. It should be emphasized that ineffective treatment should not be considered as causally related 
in the context of adverse reporting. 
7.4.1.3. The relationship to study procedures (e.g., invasive procedures such as venipuncture) should 
be assessed using the following considerations: 
7.4.1.3.1. No: Evidence exists that the adverse event has an etiology other than the study 
procedure. 
7.4.1.3.2. Yes: The adverse event occurred as a result of protocol procedures. 
 
7.5. Assessment of Severity 
7.5.1.1. AE severity should be recorded and graded according to the Grading Scale for Severity of 
Adverse Events and laboratory Abnormalities (Appendix 4). For AE associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of 
the underlying conditions; which might not be in agreement with the grading of the laboratory 
abnormality. 
7.5.1.2. The distinction between the seriousness and the severity of an AE should be noted. Severe is a 
measure of intensity; a severe reaction is not necessarily a serious reaction. For example, a 
subject might have a headache that is described as severe, but would not be considered a SAE 
unless it met one of the criteria for serious events. 
 
7.6. Toxicity Management 
7.6.1. All clinical events and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3 and as outlined below. 
7.6.1.1. Clinical events and clinically significant laboratory abnormalities will be graded according to the 
Grading Scale for Severity of Adverse Events and laboratory Abnormalities (Appendix 4). 

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7.6.1.2. Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 5 calendar days of receiving results and before study drug discontinuation, unless 
such a delay is not consistent with good medical practice. 
7.6.1.3. Any questions regarding toxicity management should be directed to the Investigator. 
7.6.2. Grades 1 and 2 Clinical Event or Laboratory Abnormality  
7.6.2.1. Continue study drug at the discretion of the Investigator 
7.6.3. Grade 3 Clinical Event or Laboratory Abnormality 
7.6.3.1. For Grade 3 clinical event or clinically significant laboratory abnormality, study drug may be 
continued if the event is considered to be unrelated to study drug. 
7.6.3.2. For a Grade 3 clinical event or clinically significant laboratory abnormality confirmed by repeat 
testing that is considered to be related to the study drug, study drug will be withheld until the 
toxicity returns to ≤ grade 2. When restarting study drug following resolution of the adverse 
event, the study drug should be restarted at full dose. 
7.6.3.3. If following re-challenge with study drug a laboratory abnormality returns to ≥ Grade 3 and is 
considered to be related to the study drug, then the study drug will be permanently 
discontinued and the subject managed according to local practice. Recurrence of laboratory 
abnormalities considered unrelated to the study drug may not require permanent 
discontinuation. 
7.6.4. Grade 4 Clinical Events or Laboratory Abnormality 
7.6.4.1. For a Grade 4 clinical event or clinically significant laboratory abnormality confirmed by repeat 
testing that is considered to be related to the study drug, the study drug will be permanently 
discontinued and the subject managed according to local practice. The subject should be 
followed as clinically indicated until the laboratory abnormality returns to baseline or is 
otherwise explained, whichever occurs first.  
7.6.4.2. A clinically significant Grade 4 laboratory abnormality that is not confirmed by repeat testing 
should be managed according to the algorithm for the new toxicity grade. 
7.6.4.3. Study drug may be continued without dose interruption for a clinically non-significant Grade 4 
laboratory abnormality (e.g., elevated CK after significant exercise or triglyceride elevation on 
a non-fasting specimen) or a clinical event considered unrelated to the study drug, but must be 
discussed with the Investigator. 
7.6.5. ALT Flare 
7.6.5.1. Defined as: serum ALT > 10 x upper limit of normal (ULN) and > 2 times baseline value, 
confirmed with repeat testing within 7 days of original results receipt, with or without 
associated symptoms 
7.6.5.2. Management of ALT Flare 
7.6.5.2.1. When initial results are received, schedule subject to return to the clinic as soon as 
possible (ideally within 3 days of initial blood draw). During the visit, in addition to 
redrawing blood for repeat CMP testing, clinical assessment of the subject will be 
performed. The assessment should include a physical examination and evaluation of the 
subject’s mental status. 
7.6.5.2.2. If ALT elevation is confirmed, the following labs should be performed: plasma HBV DNA, 
HBV serology (HBsAg and HBsAb), HAC IgM, HCV serology, quantitative HDV RNA.  
7.6.5.2.3. Based on the results of the confirmatory tests, the following treatment modifications are 
recommended: 
7.6.5.2.3.1. Elevated liver enzymes, normal or stable total bilirubin relative to baseline 
7.6.5.2.3.1.1. If ALT levels are elevated (as specified in 7.7.5.1) with normal or stable total 
bilirubin, the subject may remain on the study drug and should be 
monitored weekly until ALT levels return to normal or Baseline level. During 
monitoring, if the ALT values remain persistently elevated, the Investigator 
will determine whether the study drug should be discontinued. 
7.6.5.2.3.2. Elevated liver enzymes, elevated total bilirubin 
7.6.5.2.3.2.1. If ALT levels are elevated (as specified in 7.7.5.1) and total bilirubin is 
confirmed to be ≥ 2 x Day 1 value and is > ULN, the investigator should 

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consider discontinuing the study drug. The subject should be monitored 
weekly until ALT and total bilirubin levels return to normal or Day 1 level. 
7.6.5.2.3.3. During monitoring, if the ALT values and the liver function tests remain persistently 
elevated, the Investigator should consider discontinuing the study drug. 
 
7.6.6. Management of Potential Hepatobiliary Toxicity 
7.6.6.1. Any subject exhibiting signs/symptoms or laboratory abnormalities suggestive of possible 
hepatobiliary toxicity should undergo thorough examination and clinical workup as deemed 
appropriate by the Investigator. Consideration should be given to appropriate imaging studies 
(e.g., ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. 
 
7.7. Criteria for discontinuation of study drug 
7.7.1. In the event of the following, study drug will be discontinued: unacceptable toxicity, subject request 
for any reason, pregnancy, development of active tuberculosis, discontinue of the study at the 
request of the IRB 
7.7.2. In the event of the following, study drug may be discontinued: in the event of significant new illness 
that compromises the ability to assess end points, lack of efficacy, subject noncompliance. 
7.7.3. In the event that study drug is discontinued, every attempt should be made to keep the subject in 
the study and continue to perform the required follow ups and procedures through to the Week 16 
Visit    
 
7.8. Management of viral rebound 
7.8.1. At any post baseline visit either (1) an HIV-1 RNA ≥ 50 copies/mL for subjects who were <50 at 
baseline or (2) an increase by 1 log for subjects who were ≥ 50 copies at baseline, will be repeated 
for confirmation within 4 weeks of the original test result. If confirmatory testing is ≥ 200, HIV-1 
genotype will be performed on the confirmatory sample. Subject may be withdrawn from the study 
at investigators discretion if resistance suggested by results. If no resistance is found, repeat viral load 
should be repeated again 4 weeks later.  
 
 
8. Statistical Considerations 
8.1. Statistical and Analytic Plans 
8.1.1. All statistical methods will be based on the International Conference on Harmonization (ICH) E9 
document “Statistical Principles for Clinical Trials”.  
8.2. Hypotheses –  
8.2.1. Part 1 is exploratory  
8.2.1.1. Primary Endpoint  
8.2.1.1.1. Percentage of subjects reporting suboptimal adherence to ART therapy on the MAAS. 
Optimal adherence is measured as a score of 90% or better on Rasch score. 
8.2.1.2. Secondary Endpoints  
8.2.1.2.1. To assess the psychometric properties of the Midland ART Adherence Survey. We will 
employ a Rasch statistical approach.  Rasch Analysis (RA) is a unique approach of 
mathematical modeling based upon a latent trait and accomplishes stochastic 
(probabilistic) conjoint additivity (conjoint means measurement of persons and items on 
the same scale and additivity is the equal-interval property of the scale). 
8.2.1.2.2. Identify and classify the case mix or heterogeneity of subjects who report suboptimal 
and optimal adherence. Optimal adherence is measured as a Rasch score of better than 

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90% on the Midland AD Adherence scale.  Suboptimal is any score 90% or below. Rasch 
scores range from 0% (no adherence) to 100% (perfect adherence). 
8.2.2. Part 2 
8.2.2.1. Primary Endpoint  
8.2.2.1.1. Percentage of subjects reporting suboptimal adherence, analyzed by intention to treat, 
from baseline to 16 weeks. 
8.2.2.1.1.1. We hypothesize that a minimum of 85% of subjects taking DRV/COB/FTC/TAF will 
demonstrate an optimal adherence score from baseline to four-months as 
measured by the Midland ART Adherence Survey. Optimal adherence is defined as 
a Rasch score greater than or equal to 90%.  Rasch scores range from 0% (no 
adherence) to 100% - (perfect adherence). 
8.2.2.2. Secondary Endpoints. These are descriptive endpoints so no hypotheses are tested.  
8.2.2.2.1. Change at 4 months from baseline in tolerability measured by standardized patient 
reported outcome questionnaire 
8.2.2.2.2. Percentage of subjects with greater than or equal to 90% by pill count 
8.2.2.2.3. Proportion of subjects that have HIV-1 RNA ≥ 50 copies/mL at baseline and at month 4 
8.2.2.2.4. Proportion of subjects with significant changes at 4 months from baseline in serum 
creatinine, AST or ALT 
8.2.2.2.5. Change at 4 months from baseline in absolute and percentage CD4. 
8.2.2.2.6. Change at 4 months from baseline in weight 
8.2.2.2.7. Number of drug discontinuation for any reason 
8.3. Analysis Datasets 
8.3.1. Demographic: 
8.3.1.1. This dataset contains all subjects’ demographic data (i.e., Age, Race, and Gender), disposition 
data (i.e., Date patient withdrew from the study), and key dates such as date of first dose, date 
of last collected Case Report Form (CRF) and duration on treatment. The dataset has the format 
of one observation per subject.  
8.3.2. Laboratory: 
8.3.2.1. This dataset contains all subjects’ laboratory data, in the format of one observation per subject 
per test code per visit per accession number. Here, we derive the study visits according to the 
study window defined in the SAP, as well as re-grade the laboratory toxicity per protocol. If the 
laboratory data are collected from multiple local lab centers, this analysis dataset will also 
centralize the laboratory data and standardize measurement units by using conversion factors. 
8.3.3. Intent-to-Treat: 
8.3.3.1. This dataset contains derived primary and secondary endpoint variables from all subjects 
initially enrolled in the study. This dataset has the format of one record per subject per analysis 
period. 
8.3.4. Modified-Intent-to-Treat: 
8.3.4.1. This dataset contains derived primary and secondary endpoint variables from all subjects who 
took one dose of the treatment medications. This dataset has the format of one record per 
subject per analysis period. 
8.3.5. Vital Sign: 
8.3.5.1. This dataset contains all subjects’ vital signs collected during the trial. This dataset has the 
format of one observation per subject per vital sign per visit, similar to the structure for the 
laboratory analysis dataset.  
8.3.6. Adverse Event: 
8.3.6.1. This dataset contains all adverse events (AEs) reported including serious adverse events (SAEs) 
for all subjects. A treatment emergent flag, as well as a flag to indicate if an event is reported 
within 30 days after the subject permanently discontinued from the study, will be calculated. 
This dataset has a format of one record per subject per adverse event per start date. 

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8.3.7. Medication: 
8.3.7.1. This dataset contains the subjects’ medication records including concomitant medications and 
other medications taken either prior to the beginning of study or during the study. This dataset 
has a format of one record per subject per medication taken per start date. Incomplete and 
missing medication start or stop dates will be imputed using instructions defined in the SAP. 
8.3.8. Safety: 
8.3.8.1. This dataset contains data with one record per subject per analysis period to capture safety 
parameters for all subjects. 
8.4. Description of Statistical Methods 
8.4.1. General Approach 
8.4.1.1. When a trial is designed so that more than one study endpoint or comparison could lead to a 
conclusion that effectiveness was established, testing each endpoint separately at alpha 0.05 
will inflate the Type I error rate and overstate the statistical significance. Therefore, we will use 
the primary endpoint from Part 2 as our measure at the 0.05 level to reduce the potential for 
a Type I error rate.  
8.4.1.2. After the data have been cleaned, we will examine the distribution and dispersion of data 
through descriptive numerical summaries and graphical tools such as scatter plots and box 
plots, probability plots, scatter matrix plots, co-plots, and trellis graphics to assess 
distributional assumptions and relationships among important variables. Before attempting a 
longitudinal analysis of the change in our outcomes using a mixed, generalized linear model, 
we will use profile plots, empirical summary plots and correlograms to guide us in the 
formulation of our model.   
8.4.1.3. All data will be summarized. For baseline characteristics and safety outputs a total overall 
column will be included to summarize all subjects. Where appropriate, data will be summarized 
by visit. In summary tables of continuous variables, the minimum and maximum statistics will 
be presented to the same number of decimal places as the original data. The arithmetic mean 
(AM), median, 95% confidence interval (CI), standard deviation (SD) and standard error (SE) 
will be presented to one more decimal place than the original data.  
8.4.1.4. In summary tables of categorical variables, counts and percentages will be used. In non-
parametric summaries and analyses the minimum and maximum will be presented to the same 
number of decimal places as the original data. The mean, median, lower and upper quartiles 
will be presented to one more decimal place than the original data. The median difference and 
95% CI will only be presented in statistical analysis outputs.  
8.4.1.5. Preliminary analyses will examine descriptive and clinical characteristics at baseline. Stata 
(Version 16.1) and R (version 3.6.0) statistical packages will be used for all data analysis. 
8.5. Part 1 –  
8.5.1. Analysis of Primary End-Point 
8.5.1.1. The dependent variable is measured on an ordinal scale (Midland ART Adherence Survey). 
However, employing Rasch analysis we will convert the data to a standardized range from 0 to 
100, where 100 is perfect adherence and zero (0) is complete failure to adhere.  Using this scale 
we will examine the proportion of subjects who meet or exceed 90% adherence. 
8.5.2. Analysis of Secondary End-Points 
8.5.2.1. To assess the psychometric properties of the Midland ART Adherence Survey, we will employ 
six criteria used in the Rasch approach to evaluating rating scale effectiveness. First, a minimum 
of 10 observations should be in each category. Second, the shapes of the probability curves 
should be peaked for each category. Third, the average category measures should increase 
with the rating scale categories. Fourth, the OUTFIT mean square statistics should be less than 
1. Fifth, threshold calibrations should increase with rating scale category. Sixth, the category 
thresholds should be at least 1.4 logits apart and no more than 5 logits apart.  
8.5.2.2. Identify and classify the case mix or heterogeneity of subjects who report suboptimal 
adherence we will use latent class analysis (LCA); which allows us to identify a finite number of 
latent subgroups and to explore how treatment effect varies across these subgroups. Such 
person-centered approaches transcend limitations imposed by diagnostic categories and 

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classify subjects into latent homogenous classes based on similar response patterns. Latent 
subgroups of subjects are compared with reference to shape (qualitative differences) symptom 
levels (quantitative differences). 
  
8.6. Part 2 –  
8.6.1. Primary Endpoint 
8.6.1.1. Percentage of subjects reporting suboptimal adherence, analyzed by intention to treat, from 
baseline to four-months using Rasch scores. The hypothesis testing will be carried out at the 
5% (2-sided) significance level unless otherwise specified. P-values will be rounded to three 
decimal places. P-values less than 0.001 will be reported as <0.001 in tables. P-values greater 
than 0.999 will be reported as >0.999. 
8.6.1.2. We hypothesize that a minimum of 85% of subjects taking DRV/COB/FTC/TAF will demonstrate 
optimal adherence from baseline to four-months as measured by the Midland ART Adherence 
Survey. Optimal adherence is defined as a Rasch score greater than or equal to 90%.  Rasch 
scores range from 0% (no adherence) to 100% (perfect adherence). 
8.7. Part 2 - Analysis of Secondary End-Points 
8.7.1. These are descriptive endpoints so no hypotheses are tested.  
8.7.1.1. Change at 4 months from baseline in tolerability measured by standardized patient reported 
outcome questionnaire. 
8.7.1.2. Percentage of subjects with greater than or equal to 90% by pill count 
8.7.1.3. Proportion of subjects that have HIV-1 RNA ≥ 50 copies/mL at baseline and at month 4 
8.7.1.4. Proportion of subjects with significant changes at 4 months from baseline in serum creatinine, 
AST or ALT 
8.7.1.5. Change at 4 months from baseline in absolute and percentage CD4. 
8.7.1.6. Change at 4 months from baseline in absolute and percentage weight 
8.7.1.7. Number of drug discontinuation for any reason 
 
8.7.2. All data will be summarized. For baseline characteristics and safety outputs a total overall column will 
be included to summarize all subjects. Data will be summarized by visit. In summary tables of 
continuous variables, the arithmetic mean (AM), median, 95% confidence interval (CI), standard 
deviation (SD) and standard error (SE) will be presented to one more decimal place than the original 
data. In summary tables of categorical variables, counts and percentages will be used. 
8.7.3. We will identify and classify the case mix or heterogeneity of subjects adherence we will using latent 
class analysis (LCA); which allows us to identify a finite number of latent subgroups and to explore 
how treatment effect varies across these subgroups. Using the clinical, psychosocial and demographic 
variables we will classify subjects into latent homogenous classes based on similar response patterns. 
8.7.4. Using the latent classes identified above we will  use class membership (latent class) in a as a predictor 
of a distal standardized outcome adherence range from 0 to 100.  
8.8. Sample 
8.8.1. All subjects who meet pre-determined criteria from Adherence Survey and meet other eligibility 
requirements will be offered enrollment into Part II of the study. As Part 1 of the study is tied to Part 
2, we will employ the same sampling formulation for minimum sample size. 
8.8.2. We follow the work of Viechtbauer et al (2015) to calculate sample size. For encountering a reduction 
in primary-end-points of 10%, with a 95% confidence interval we use the formula n=ln 
(1 − 0.95)/ ln(1 − 0.10 ) = 30 subjects are needed. This will ensure that we will encounter at least one 
reduction of the primary end-point at a 95% confidence level. 
 
 
 
 
 

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9. Responsibilities 
 
9.1. Good Clinical Practice 
9.1.1. The rights and welfare of the individual clinical research subject must always be the paramount 
consideration in conducting clinical research. Accordingly, clinical research must be conducted in a 
manner that protects the rights, welfare and confidentiality of the human subject and also assures 
data credibility by protecting the integrity of accurate data that has been demonstrably collected 
according to the approved protocol. 
 
9.2. Investigator Responsibilities 
9.2.1. The Investigator is responsible for:  
 
9.2.1.1. Ensuring 
that 
the 
study 
is 
conducted 
according 
to 
the 
signed 
investigator 
statement/agreement, the investigational plan (study protocol), applicable regulations 
9.2.1.2. Ensuring that all persons assisting with the trial are adequately informed about the protocol, 
the study drug, their trial-related duties and functions 
9.2.1.3. Protection of the rights, safety, and welfare of subjects under the investigator’s care 
9.2.1.4. Control of the study drug included in the investigation. 
9.2.1.5. Assuring that each subject’s informed consent is obtained appropriately 
9.2.1.6. Proper delegation of authority for the conduct of various aspects of the study so that the 
investigator retains control and knowledge of the study 
 
9.3. Control of Study Drug 
9.3.1. The investigator shall control the study drug. The Investigator is responsible to ensure that: 
9.3.1.1. The study drug is administered only to subjects under the investigator’s personal supervision 
or under the supervision of a qualified sub-investigator responsible to the investigator. 
9.3.1.2. The study drug is not to be supplied/provided to any person not authorized to receive it. 
9.3.1.3. Adequate records of the disposition of the study drug are maintained, including dates, 
quantity, receipt, distribution to subjects, and disposition.  
9.4. Medical Decision Making 
9.4.1. Primary Investigator or sub-investigator must be designated as responsible for all trial-related 
medical decisions. Medical decisions must be made by a qualified person permitted by state licensure 
laws to make or enact such decisions. The investigator should: 
9.4.2. Ensure that adequate medical care is provided to a subject for any adverse events related to the trial, 
during and as follow-up to a subject's participation. 
9.4.3. Inform a subject when medical care is needed for intercurrent illness (es) of which the 
investigator/sub-investigator becomes aware. 
9.4.4. Inform the subject's primary physician about the subject's participation in the trial if the subject 
agrees to the primary physician being informed, and has signed a HIPAA Authorization form 
permitting such disclosure. 
9.5. IRB/IEC Review and Approval 
9.5.1. The investigator shall assure that initial and continuing review of the proposed clinical study is 
performed according to the policies and procedures of the Central Institutional Review Board (IRB), 
as well as with any other IRB that has jurisdiction. 
9.5.2. Continuous approval from the IRB must be maintained. 
9.5.3. All unanticipated problems involving risk to human subjects or others are promptly reported to the 
IRB. All serious adverse events are reported to the IRB within twenty-four hours of time investigator 
is aware of the event. 
9.5.4. Any changes in the research activity are promptly reported to the IRB. 
9.5.5. No changes are made in the research without IRB approval, except where necessary to eliminate 
apparent immediate hazards to human subjects. 
9.6. Informed Consent 

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9.6.1. The Investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and potential 
hazards of the study and before undertaking any study related procedures. The investigator must use 
the most current IRB/IEC-approved consent form for documenting written informed consent. Each 
informed consent (or assent as applicable) will be appropriately signed and dated by the subject’s 
legally authorized representative and the person conducting the consent discussion, and also by an 
impartial witness if required by IRB/IEC or local requirements. The consent form will inform subjects 
about sample retention. 
9.7. Confidentiality 
9.7.1. The investigator will assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. All information and data will be collected by the 
investigator. All collected data concerning participants or their participation in this study will be 
considered confidential and maintained in a HIPAA-compliant electronic medical recording system. 
Subject data pertinent to the study will be de-identified and access limited only to personnel directly 
involved in this research study. All data used in the analysis and reporting of this evaluation will be 
used in a manner without identifiable reference to the participant. Study data will not be transmitted 
nor disclosed to a third-party. Paper records will be kept in secure files and electronic records will be 
password protected. 
9.8. Study Files and Retention of Records 
9.8.1. The investigator shall keep and maintain adequate and accurate records, including: 
9.8.2. Case histories on each individual study subject that record all observations and other data pertinent 
to the investigation 
9.8.3. Screening, enrollment, and informed consent documentation; demonstrating that informed consent 
was obtained prior to participation in the study 
9.8.4. Study reports, including reports of progress, safety, financial disclosure and final completion 
9.9. Records retention  
9.9.1. Midland Research Group Inc.  will use on-site facility and if storage becomes unavailable due to 
capacity of documents, then Midland Research Group Inc will use an offsite facility.  
9.9.2. FDA regulation requires an investigator to retain records a minimum of two years after the close of 
the study or after the records are no longer required to support a drug or marketing application, 
whichever is longer. 
9.9.3. Contract commitments must be met. 
9.9.4. Record transfer or record destruction should be verified and documented. 
9.10. Case Report Forms 
9.10.1. For each subject consented, a study file will be completed by an authorized study staff member 
who has completed training for this function. The study file will only capture the data required per 
the protocol schedule of events and procedures. The Inclusion/Exclusion Criteria and Enrollment 
should be completed only after all data related to eligibility have been received. Subsequent to data 
entry, a second staff member will perform source data verification.  
9.11. Study Drug Accountability and Return 
9.11.1. Unused study drug supplies will be destroyed. Investigator will assist with disposal procedures and 
provide appropriate instruction for destruction of unused study drug supplies.  
9.12. Protocol Compliance 
9.12.1. The Investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
9.13. Sponsor Responsibilities 
9.14. Protocol Modifications 
9.14.1. Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the Investigator, who must submit all protocol modifications to the IRB in accordance 
with local requirements and receive documented IRB approval before modifications can be 
implemented. 
 
 

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9.15. Study Report and Publications 
9.15.1. The Investigator is responsible for submitting any reports within time periods and according to 
procedures called for by: 
9.15.1.1. 
Midland Research Group Inc . or applicable division or departmental policy or procedures, 
including the Institutional Review Board (IRB) 
9.15.1.2. 
Contractual agreements with collaborators, etc. 
9.16. Payment Reporting 
9.16.1. Investigators and their study staff may be asked to provide services performed under this protocol. 
If required under applicable statutory and regulatory requirements, Midland Research Group Inc. will 
capture and disclose to Federal and State agencies any expenses paid or reimbursed for such services, 
including any clinical trial payments, meal, travel expenses or reimbursements, consulting fees, and 
any other transfer of value. 
9.17. Access to Information for Monitoring, Auditing or Inspection 
9.17.1. As per contract 
9.18. Study Discontinuation 
9.18.1. The investigator reserves the right to terminate the study at any time. Should this be necessary, 
they will arrange discontinuation procedures and notify the appropriate regulatory authorities and 
the IRB. In terminating the study, the Investigator will assure that adequate consideration is given to 
the protection of the subjects’ interests. 
9.19. PUBLICATIONS  
9.19.1. As per contract 
 
 
 References 
 
1) Ortego C, et al. Adherence to highly active antiretroviral therapy (HAART): a meta-analysis. AIDS and 
Behavior. 2011;15:1381–1396. doi: 10.1007/s10461-011-9942-x. 
2) Robbins RN, Spector AY, Mellins CA, Remien RH. Optimizing ART Adherence: Update for HIV Treatment 
and Prevention. Current HIV/AIDS reports. 2014;11(4):423-433. doi:10.1007/s11904-014-0229-5. 
3) Orkin C, Molina JM, Negredo N, et al; EMERALD Study Group. Efficacy and safety of switching from 
boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet 
darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically 
suppressed HIV-1 (EMERALD): a phase 3, randomized, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-
e34. 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX  1:  Midland ART Adherence Survey (MAAS) 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
Page 22 of 38 
Midland ART Adherence Survey 
 
 
Survey #_________ 
Age:  18-35  36-49   50-65   66-99  
  Ethnicity: _____________ 
   Gender: __________   
 
How long on ART?  <1 year 
 1-5 years  
 6-10 years 
 11-15 years 
 16 or more years 
1. Do you sometimes forget to 
take your HIV medications? 
3. Have you ever not taken your 
meds because you felt worse 
when you took it? 
4. When you travel or leave 
home, do you sometimes forget 
to bring along your 
medications? 
5. Did you take your HIV 
medicine yesterday? 
6. When you feel like your 
health is good, do you 
sometimes stop taking your 
medicine? 
7. Do you ever miss doses of 
your medications because of 
side effects from them? If so, 
what side effects? 
 
 Yes  
  No 
 
 Yes  
  No 
 
 Yes  
  No 
 
 Yes  
  No 
 
 Yes  
  No 
 
 
 Yes  
  No  
________________________ 
 
 
Current prescribed HIV regimen: 
 
Biktarvy 
 
Genvoya 
 
Julica 
 
Triumeq 
 
Isentress/Isentress HD 
 
Stribild 
 
Dulera 
 
Tivicay 
 
Symtuza 
 
Atripla 
 
Complera 
 
Odefsey 
 
Reyataz or Evotaz 
 
Prezista or Prezcobix 
 
Descovy 
 
Truvada 
 
Epzicom 
 
Edurant 
 
Intelence 
 
Sustiva 
 
Selzentry 
 
 
8. How often do you take your HIV medications?  
 ALWAYS –never miss a dose  
 ALMOST ALWAYS-miss 1-2 times a month  
 USUALLY-miss 3- 5 times a month 
 SOMETIMES-miss more than 5 times, but take more than 5 times a 
month  
 RARELY-take 3- 5 times a month 
 ALMOST NEVER-take 1-2 times a month 
 NEVER-do not take the medication  
 
9. How many days in the last week did you not take your HIV medication?  ______  
10. How many days in the last month did you not take your HIV medication?  ______  
11. What is your biggest issue with being able to take your medication: _____________________ 
We are looking at some ways to help our patients with their medications. Would it be ok to share your responses 
with your provider if we think we might have some options for you?        Yes                 No

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 2: Self-Completed HIV Symptom Index (HIV-SI) 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
Page 23 of 38 
Self-completed HIV Symptom Index15 
INSTRUCTIONS: The following questions ask about symptoms you might have had during the past four weeks. 
Please answer the following questions by placing a checkmark in the appropriate box. 
Symptom 
Did not have 
this symptom 
Symptom 
did not 
bother me 
Symptom 
bothers me
a little 
Symptom 
bothers me 
Symptom 
bothers me 
a lot 
Fatigue or loss of energy 
 
 
 
 
 
Fevers, chills or sweats 
 
 
 
 
 
Feeling dizzy or lightheaded 
 
 
 
 
 
Pain, numbness or tingling in the hands or 
feet 
 
 
 
 
 
Trouble remembering 
 
 
 
 
 
Nausea or vomiting 
 
 
 
 
 
Diarrhea or loose bowel movements 
 
 
 
 
 
Felt sad, down, or depressed 
 
 
 
 
 
Felt nervous or anxious 
 
 
 
 
 
Difficulty falling or staying asleep 
 
 
 
 
 
Skin problems, such as rash, dryness or 
itching 
 
 
 
 
 
Cough or trouble catching your breath 
 
 
 
 
 
Headache 
 
 
 
 
 
Loss of appetite or a change in the taste of 
food 
 
 
 
 
 
Bloating, pain, or gas in your stomach 
 
 
 
 
 
Muscle aches or joint pain 
 
 
 
 
 
Problems with having sex, such as loss of 
interest or lack of satisfaction 
 
 
 
 
 
Changes in the way your body looks such as 
fat deposits or weight gain 
 
 
 
 
 
Problems with weight loss or wasting 
 
 
 
 
 
Hair loss or changes in the way your hair 
looks 
 
 
 
 
 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 24 of 38 
EXHIBIT B 
Requirements for Safety Data Collection and Reporting 
1. OVERVIEW 
As the sponsor of the Study, INSTITUTION and PRINCIPAL INVESTIGATOR shall be solely responsible for complying, 
within the required timelines, any safety reporting obligation to competent Health Authorities, IRB/ECs and any 
participating (co or sub) investigators, as defined in applicable laws and regulations.  For the purposes of this 
EXHIBIT, safety data includes adverse events, product quality complaints (PQCs), and special situations including 
pregnancies. 
 
The INSTITUTION and PRINCIPAL INVESTIGATOR will provide safety information to the COMPANY on adverse events, 
special situations including pregnancies and product quality complaints as defined within this EXHIBIT. 
 
2. Management of Safety Data 
This Study has been designated as an interventional study.  As such, all adverse events, special situations including 
pregnancies and product quality complaints will be reported as described in this exhibit from the time a subject has 
signed and dated an Informed Consent Form (ICF) until 30 days after the last documented use of a product under 
study within the study. 
 
For the purposes of this study, the J&J medicinal product is: Symtuza 
3. Definitions 
3.1. Adverse Event (AE) 
An adverse event is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with 
the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non- 
investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. 
(Definition per International Conference on Harmonization [ICH]) 
This includes any occurrence that is new in onset or aggravated in severity or frequency from the baseline condition, 
or abnormal results of diagnostic procedures, including laboratory test abnormalities. 
 
3.2. Adverse Events of Special Interest  
Adverse events of special interest are events that the COMPANY is actively monitoring as a result of a previously 
identified signal (even if non-serious). No adverse events of special interest will be collected for this study. 
 
3.3. Individual Case Safety Report (ICSR) 
A valid ICSR must contain the four minimum criteria required to meet regulatory reporting requirements. 
• 
an identifiable subject (but not disclosing personal information such as the subject’s name, initials or address) 
• 
an identifiable reporter (investigational site) 
• 
a J&J medicinal product 
• 
an adverse event, outcome, or certain special situations 
 
The minimum information required is: 
• 
suspected J&J medicinal product (doses, indication) 
• 
date of therapy (start and end date, if available) 
• 
batch or lot number, if available 
• 
subject details (subject ID and country) 
• 
gender 
• 
age at AE onset 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 25 of 38 
• 
reporter ID 
• 
adverse event detail (AE verbatim in English), onset date, relatedness, causality, action taken, outcome, (if 
available) 
• 
J&J protocol ID 
 
3.4. Product Quality Complaint (PQC) 
A product quality compliant is defined as any suspicion of a product defect related to a potential quality issue 
during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage or distribution 
of the product, or delivery system.  Not all PQCs involve a subject.  Lot and batch numbers are of high significance 
and need to be collected whenever available. 
 
Examples of PQC include but not limited to: 
• 
Functional Problem: e.g., altered delivery rate in a controlled release product 
• 
Physical Defect:  e.g. abnormal odor, broken or crushed tablets/capsules 
• 
Potential Dosing Device Malfunction: e.g., autoinjector button not working, needle detaching from 
syringe 
• 
Suspected Contamination 
• 
Suspected Counterfeit 
 
3.5. Serious Adverse Event (SAE) 
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human Use 
is any untoward medical occurrence that at any dose: 
 
• 
Results in death 
• 
Is life-threatening 
(The subject was at risk of death at the time of the event. It does not refer to an event that hypothetically 
might have caused death if it were more severe.) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly/birth defect 
• 
Is a suspected transmission of any infectious agent via a medicinal product 
• 
Is medically important* 
 
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is also 
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 should usually be considered serious. 
 
NOTE: DEATH FOR ANY REASON SHOULD BE REPORTED AS A SERIOUS ADVERSE EVENT. 
 
3.5.1. Hospitalization 
For reports of hospitalization, it is the sign, symptom or diagnosis which led to the hospitalization that is the 
serious event for which details must be provided. 
 
Any event requiring hospitalization or prolongation of hospitalization that occurs during the study must be 
reported as a serious adverse event, except hospitalizations for the following: 
• 
Hospitalizations not intended to treat an acute illness or adverse event (e.g., social reasons such as 
pending placement in long-term care facility) 
• 
Surgery or procedure planned before entry into the study. [Note: Hospitalizations that were planned 
before the start of data collection and where the underlying condition for which the hospitalization 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 26 of 38 
was planned has not worsened will not be considered serious adverse events. Any adverse event that 
results in a prolongation of the originally planned hospitalization is to be reported as a new serious 
adverse event.] 
 
3.5.2. Life-Threatening Conditions 
The cause of death of a subject in a study 30 days of the last dose of study drug, whether or not the event is 
expected or associated with the study drug, is considered a serious adverse event. 
4. Unlisted (Unexpected) Adverse Event/Reference Safety Information 
 
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable product 
reference safety information. For a medicinal product(s) with a marketing authorization, the expectedness of an 
adverse event will be determined by whether or not it is listed in the applicable product information. 
https://www.symtuza.com/  
 
5. Special Reporting Situations  
Safety events of interest for a J&J medicinal product that require expediting reporting and/or safety evaluation 
include, but are not limited to: 
• 
Drug exposure during pregnancy (maternal and paternal) 
• 
Overdose of a J&J medicinal product  
• 
Exposure to a J&J medicinal product from breastfeeding  
• 
Suspected abuse/misuse of a J&J medicinal product 
• 
Inadvertent or accidental exposure to a J&J medicinal product 
• 
Medication error (includes potential, intercepted or actual) involving a J&J product (with or without patient 
exposure to the J&J Product(s) Under Study, e.g., name confusion)  
• 
 
• 
Suspected transmission of any infectious agent via administration of a medicinal product 
• 
Unexpected therapeutic or clinical benefit from use of a J&J medicinal product 
• 
Any failure of expected pharmacological action (i.e., lack of effect) of a J&J medicinal product 
 
These safety events may not meet the definition of an adverse event; however, from a COMPANY perspective, 
they are treated in the same manner as adverse events. Special situations should be recorded on the Adverse 
Event page of the CRF. 
Any special situation that meets the criteria of a serious adverse event should be recorded on a Serious Adverse 
Event Report Form and be reported to the COMPANY within 24 hours of becoming aware of the event. 
 
6. Pregnancy  
All initial reports of pregnancy must be reported to the COMPANY by the PRINCIPAL INVESTIGATOR within 24 hours 
of becoming aware of the event using the Serious Adverse Event Form. Abnormal pregnancy outcomes (e.g. 
spontaneous abortion, fetal death, stillbirth, congenital anomaly, ectopic pregnancy) are considered serious adverse 
events and must be reported using the Serious Adverse Event Form.  
Any subject who becomes pregnant during the study must be promptly withdrawn from the study and discontinue 
further study treatment. 
Because the effect of the J&J medicinal product on sperm is unknown, pregnancies in partners of male subjects 
exposed to a J&J medicinal product will be reported by the PRINCIPAL INVESTIGATOR within 24 hours of their 
knowledge of the event using the Serious Adverse Event Form.  Depending on local legislation this may require prior 
consent of the partner. 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the infant will be 
required. 
 
 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 27 of 38 
 
7. Maintenance of Safety Information 
All safety data should be maintained in a clinical database in a retrievable format. The INSTITUTION and PRINCIPAL 
INVESTIGATOR shall provide all adverse events, both serious and non-serious, in report format. However, in certain 
circumstances more frequent provision of safety data may be necessary, e.g. to fulfill a regulatory request, and as such 
the data shall be made available within a reasonable timeframe at the COMPANY’s request. 
 
8. Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for J&J Medicinal Products to the 
COMPANY 
All adverse events and special situations, whether serious or non-serious, related or not related, following exposure to 
a J&J medicinal product are to be documented by the investigator and recorded in the CRF and in the subject’s source 
records. Investigators must record in the CRF their opinion concerning the relationship of the adverse event to a J&J 
medicinal product.  
All (serious and non-serious) adverse events reported for a J&J medicinal product should be followed-up in accordance 
with clinical practice. 
 
8.1. SAEs, Adverse Events of Special Interest and Special Reporting Situations 
All serious adverse events that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject's participation in the study, must be followed until any of the following occurs: 
• 
The event resolves 
• 
The event stabilizes 
• 
The event returns to baseline, if a baseline value/status is available 
• 
The event can be attributed to agents other than the study drug or to factors unrelated to study conduct 
• 
It becomes unlikely that any additional information can be obtained (subject or health care practitioner 
refusal to provide additional information, lost to follow-up after demonstration of due diligence with follow-
up efforts) 
 
The INSTITUTION and the PRINCIPAL INVESTIGATOR) will transmit all SAEs, Adverse Events of Special Interest and 
special situations following exposure to a J&J product under study in a form provided by the COMPANY in 
accordance with Section 9, Transmission Methods, in English within 24-hours of becoming aware of the event(s). 
 
In the event the study is blinded, the PRINCIPAL INVESTIGATOR will submit an unblinded SAE or pregnancy 
exposure report to COMPANY. 
 
All follow-up information for serious adverse events that are not resolved at the end of the study or by the time 
of patient withdrawal must be reported directly by the PRINCIPAL INVESTIGATOR, within 24 hours becoming 
aware, to the COMPANY using the COMPANY’s Serious Adverse Event Report  
 
All available clinical information relevant to the evaluation of a related SAE, Adverse Events of Special Interest, 
serious ADR or special situation is required. 
 
• 
The INSTITUTION and/or PRINCIPAL INVESTIGATOR is responsible for ensuring that these cases are complete 
and if not are promptly followed-up. A safety report is not considered complete until all clinical details 
needed to interpret the case are received. Reporting of follow-up information should follow the same 
timeline as initial reports. 
 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 28 of 38 
• 
Copies of any and all relevant extraordinary (not including routine initial or follow-up ICSR submission) 
correspondences with regulatory authorities and ethics committees regarding any and all serious adverse 
irrespective of association with the J&J Product under study, are to be provided to the COMPANY using a 
transmission method in Section 9 within 24 hours of such report or correspondence being sent to applicable 
health authorities. 
 
8.2. Non-Serious AEs 
All non-serious adverse events should be reported to COMPANY according to the timeframe outlined in the 
Research Funding Agreement section entitled Reporting of Data. 
 
8.3. PQC Reporting 
A PQC may have an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting 
and analysis of PQC information from studies are crucial for the protection of patients, investigators, and the 
COMPANY, and are mandated by regulatory agencies worldwide. The COMPANY has established procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of PQC information. Lot 
and/or Batch #s shall be collected or any reports failure of expected pharmacological action (i.e., lack of effect). 
The product should be quarantined immediately and if possible, take a picture. 
 
All initial PQCs involving a J&J medicinal product under study must be reported to the COMPANY by the PRINCIPAL 
INVESTIGATOR within 24 hours after being made aware of the event. The J&J contact will provide additional 
information/form to be completed. 
 
If the defect for a J&J medicinal product under study is combined with either a serious adverse event or non-
serious adverse event, the PRINCIPAL INVESTIGATOR must report the PQC to the COMPANY according to the 
serious adverse event reporting timelines.  A sample of the suspected product should be maintained for further 
investigation if requested by the COMPANY. 
 
9. Reporting Procedures for Reporting Safety Data and Product Quality Complaints (PQCs) for Non-J&J Medicinal 
Products  
For SAEs, special reporting situations and PQCs following exposure to a non-J&J medicinal product under study, the 
PRINCIPAL INVESTIGATOR should notify the appropriate regulatory/competent authority or the manufacturer of 
that medicinal product (in the absence of appropriate local legislation) as soon as possible. 
10. Transmission Methods 
The following methods are acceptable for transmission of safety information to the COMPANY: 
• 
Electronically via Janssen SECURE Email service (preferred) 
• 
For business continuity purposes, if SECURE Email is non-functional: 
o 
Facsimile (fax), receipt of which is evidenced in a successful fax transmission report 
• 
Telephone (if fax is non-functional). 
 
Please use the contact information and process information provided by the COMPANY.  
 
11. SAEs Listing 
At a minimum, on a semi-annual basis and at the end of the Study, COMPANY will provide to the INSTITUTION and/or 
PRINCIPAL INVESTIGATOR, a listing of all SAEs reported to the COMPANY. SPONSOR and/or PRINCIPAL INVESTIGATOR 
will review this listing and will resolve any discrepancies with the data provided by the COMPANY. 
 
12. Dissemination of Safety Information from COMPANY to INSTITUTION/PRINCIPAL INVESTIGATORS 

 
Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc 
 
APPENDIX 3:  Exhibit B, Safety and Data Collection and Reporting 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 29 of 38 
PRINCIPAL INVESTIGATOR will be responsible for submitting IND safety reports for the Study Product to INSTITUTION’s 
IRB in accordance with Federal regulations 21 CFR 312.66.  The PRINCIPAL INVESTIGATOR will provide a copy of each 
IND safety report to sub-investigators where the study design is either a multi-center or cooperative study. 
COMPANY agrees to provide to the PRINCIPAL INVESTIGATOR IND safety reports for the J&J Medicinal Product as they 
become available until all subjects in the Protocol have completed their last Study visit according to the Protocol (i.e. 
Last Subject Last Visit has occurred).  
 
13. Contacting COMPANY Regarding Safety 
The names (and corresponding contact information) of the individuals who should be contacted regarding safety 
issues will be provided separately by the COMPANY. 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 30 of 38 
APPENDIX 4  GRADING SCALE FOR SEVERITY OF ADVERSE EVENTS AND LABORATORY ABNORMALITIES 
Laboratory Tests 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
8.5-10.0 
7.5-8.49 
6.5-7.49 
<6.5 
ANC 
1000-1300 
750-999 
500-749 
<500 
Platelets 
100-125 
50-99 
25-49 
<25 
WBC 
2.0-2.5 
1.5-1.99 
1.0-1.49 
<1 
Hyponatremia 
>130 
125-129 
121-124 
<121 
Hypernatremia 
<150 
150-154 
154-159 
>159 
Hypokalemia 
>3 
2.5-3.0 
2.0-2.49 
<2.0 
Hyperkalemia 
5.6-6.0 
6.01-6.5 
6.51-7.0 
>7.0 
Hypoglycemia 
55-64 
40-54.9 
30-39.9 
<30 
Hyperglycemia, 
Fasting 
110-125 
126-250 
251-500 
>500 
Hypocalcemia 
(corrected) 
Below normal but 
above 7.8 
7.0-7.8 
6.1-6.9 
<6.1 
Hypercalcemia 
(corrected) 
Above normal but 
below 11.5 
11.5-12.5 
12.6-13.5 
>13.5 
Total Bilirubin 
Up to 1.5 ULN 
1.5-2.5 x ULN 
2.5-5.0 x ULN 
>5.0 x ULN 
BUN 
1.25-2.5 x ULN 
2.6-5.0 x ULN 
5.1-10 x ULN 
>10 x ULN 
Creatinine 
1.5-2.0 
2.01-3.00 
3.01-6.00 
>6.00 
Bicarb 
16-LLN 
11-15.9 
8-10.9 
<8.0 
Triglycerides (fasting) 
NA 
500-750 
751-1200 
>1200 
LDL (fasting) 
130-160 
161-190 
>190 
NA 
CK 
3-6 x ULN 
6.1-10 x ULN 
10.1-20 ULN 
>20 x ULN 
AST 
1.25-2.5 x ULN 
2.6-5.0 x ULN 
5.1-10 x ULN 
>10 x ULN 
ALT 
1.25-2.5 x ULN 
2.6-5.0 x ULN 
5.1-10 x ULN 
>10 x ULN 
GGT 
1.25-2.5 x ULN 
2.6-5.0 x ULN 
5.1-10 x ULN 
>10 x ULN 
Alk Phos 
1.25-2.5 x ULN 
2.6-5.0 x ULN 
5.1-10 x ULN 
>10 x ULN 
Lipase 
1.0-1.5 x ULN 
1.51-3.0 x ULN 
3.01-5.0 x ULN 
>5.0 x ULN 
Albumin 
NA 
2.0 to <LLN 
<2.0 
NA 
Hematuria 
>ULN-10 
>10-75 
>75 
NA 
Proteinuria 
1+ 
2-3+ 
4+ 
NA 
Glycosuria 
1+ 
2-3+ 
4+ 
NA 
Cardiac Arrhythmia 
Asymptomatic and no 
intervention 
indicated 
Asymptomatic and 
non-urgent 
intervention 
indicated 
Symptomatic and 
non-urgent 
intervention 
indicated 
Life threatening or 
urgent intervention 
indicated 
Cardiac 
ischemia/infarct 
NA 
NA 
Stable angina or 
testing with ischemia 
Unstable angina or 
acute MI 
Hemorrhage 
NA 
Symptomatic, no 
transfusion indicated 
Symptomatic, ≤ 2 
units PRBC’s 
transfusion indicated 
Life threatening or 
> 2 units PRBC’s 
transfusion indicated 
Hypertension 
Systolic: 140-159 
Diastolic: 90-99 
Systolic: 160-179 
Diastolic: 100-109 
Systolic: >179 
Diastolic: 110 
Life threatening (i.e. 
malignant 
hypertension) or 
requiring hospital 
admission 
Hypotension 
NA 
Symptomatic, 
corrected with oral 
fluids 
Symptomatic, IV 
fluids indicated 
Refractory shock 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
APPENDIX 4:  Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 31 of 38 
Pericardial effusion 
Asymptomatic, small 
Asymptomatic, mod-
large 
Physiologic 
consequences, no 
urgent intervention 
indicated 
Physiologic 
consequences, urgent 
intervention 
indicated 
PR prolongation 
0.21-.025 
>0.25 
Type II 2nd degree AV 
block 
Complete AV block 
Prolonged QTc 
450-470 
Or increase <30 
above baseline 
471-499 
Or increase 30-50 
above baseline 
>499 
Or increase >50 
above baseline 
Life threatening 
dysrhythmia 
Thrombus 
NA 
DVT, no intervention 
or anticoagulation 
indicated 
DVT, intervention or 
anticoagulation 
indicated 
PE or life-threatening 
embolism 
Vasovagal episode 
No LOC 
LOC 
NA 
NA 
Ventricular 
dysfunction 
NA 
Asymptomatic and 
intervention 
indicated 
New/worsening  
symptomatic CHF 
Life threatening CHF 
 
Bronchospasm 
FEV1 70-80% 
FEV1 50-69% 
FEV1 25-49% 
FEV1<25%, cyanosis 
or intubation 
Dyspnea 
On exertion, minimal, 
without impact on 
activities 
On exertion, 
moderate, with 
impact on activities 
At rest, unable to 
perform typical 
activities 
Resp failure with vent 
support indicated 
Uveitis 
Asymptomatic 
Symptomatic or 
intervention 
indicated 
Posterior or pan-
uveitis or operation 
indicated 
Disabling visual loss 
Visual changes from 
baseline 
minimal, without 
impact on activities 
moderate, with 
impact on activities 
unable to perform 
typical activities 
Disabling visual loss 
Alopecia 
Thinning detectable 
by subject 
Thinning/patchy hair 
loss detectable by 
provider 
Complete hair loss 
NA 
Rash 
Localized macular 
rash 
Diffuse rash or target 
lesions; no vesicles, 
bulla or ulceration. 
No mucosal 
involvement 
Diffuse rash or target 
lesions; with vesicles, 
few bulla or 
superficial ulceration.  
mucosal involvement 
of one site 
Extensive bullous 
lesions/more than 
one site of mucosal 
involvement, 
Stevens-Johnson 
syndrome or toxic 
epidermal necrolysis 
Pigmentation 
changes 
Slight or localized 
Marked or 
generalized 
NA 
NA 
Pruritis 
minimal, without 
impact on activities 
moderate, with 
impact on activities 
Severe, unable to 
perform typical 
activities 
NA 
Anorexia 
Mild, not decreasing 
intake 
Decreased intake, no 
significant weight loss 
Significant weight 
loss 
Aggressive 
intervention 
indicated (i.e. feeding 
tube) or life 
threatening 
Ascites 
Asymptomatic 
Symptomatic, 
Intervention 
indicated 
Symptomatic despite 
intervention 
Life threatening 
consequences 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
APPENDIX 4:  Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 32 of 38 
Cholecystitis 
NA 
Medical intervention 
indicated 
Procedure indicated 
Life threatening 
consequences 
(sepsis/perforation) 
Constipation 
NA 
Persistent, requiring 
regular use of diet 
modification, 
laxatives/enemas 
Obstipation with 
manual evacuation 
indicated 
Life threatening 
consequences 
(obstruction) 
Diarrhea 
Transient/ 
intermittent or 
increase of >3 stools 
over baseline/24 hr. 
Persistent or increase 
of 4-6 stools over 
baseline/24 hr. 
Bloody diarrhea or 
increase of >6 stools 
over baseline/24 hr. 
Life threatening 
consequences (shock) 
Dysphagia 
Able to eat usual diet 
Causes alteration of 
diet, but no medical 
intervention 
indicated 
Causes severe 
alteration of diet, 
medical intervention 
indicated 
Life threatening 
reduction of oral 
intake 
Mucositis/stomatitis 
Erythema 
Patchy Ulcerations or 
pseudomembranous 
Confluent Ulcerations 
or 
pseudomembranous 
or mucosal bleeding 
Tissue necrosis or 
diffuse mucosal 
bleeding or life 
threatening 
consequences 
Nausea 
Transient or 
intermittent 
Persistent resulting in 
decreased oral intake 
24-48 hours 
Persistent resulting in 
minimal oral intake 
>48 hours or 
aggressive 
rehydration indicated 
Life threatening 
consequences 
Pancreatitis 
NA 
Symptomatic, no 
hospitalization 
indicated 
Symptomatic, 
hospitalization 
indicated 
Life threatening 
consequences 
Proctitis 
Discomfort 
Minimal interference 
with usual activities 
or medical 
intervention 
indicated 
Unable to perfume 
usual activities or 
operative 
intervention 
indicated 
Life threatening 
consequences 
Vomiting 
Transient or 
intermittent 
Persistent resulting in 
decreased oral intake 
24-48 hours 
Persistent resulting in 
minimal oral intake 
>48 hours or 
aggressive 
rehydration indicated 
Life threatening 
consequences 
Psychiatric issues (i.e. 
anxiety, agitation, 
depression, mania, 
psychosis) 
minimal, without 
impact on activities 
moderate, with 
impact on activities 
Severe, unable to 
perform typical 
activities 
Behavior potentially 
harmful to self/others 
or unable to perform 
self-care 
AMS 
minimal, without 
impact on activities 
lethargy, with impact 
on activities 
Confusion, memory 
impairment lethargy, 
or somnolence, 
unable to perform 
typical activities 
Delirium/obtundation 
or coma 
Ataxia 
Minimal but 
detectable on exam, 
without impact on 
activities 
moderate, with 
impact on activities 
marked, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
APPENDIX 4:  Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 33 of 38 
Cognitive and 
behavior (including 
dementia and ADD) 
Minimal, without 
impact on activities. 
No special resourced 
indicated 
moderate, with 
impact on activities 
or part-time special 
resourced indicated 
marked, unable to 
perform typical 
activities or full-time 
special resourced 
indicated 
Disabling causing 
inability to care for 
self or 
institutionalization 
CNS Ischemia 
NA 
NA 
Transient ischemic 
attach 
CVA/stroke with 
neurological deficit 
Headache 
Minimal but 
detectable on exam, 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or hospitalization 
indicated 
Insomnia 
NA 
moderate, with 
impact on activities 
or part-time special 
resourced indicated 
marked, unable to 
perform typical 
activities or full-time 
special resourced 
indicated 
Disabling causing 
inability to care for 
self 
Neuromuscular 
Weakness 
Asymptomatic but 
detectable on exam, 
without or minimal 
impact on activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or respiratory 
failure 
Sensory alteration 
Asymptomatic but 
detectable on exam, 
without or minimal 
impact on activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or respiratory 
failure 
Seizure, new onset 
NA 
1 seizure 
2-4 seizures 
Prolonged or 
repetitive seizures or 
difficult to control 
Seizure, pre-existing 
NA 
Increased frequency, 
no change in 
character 
Change from baseline 
in either duration or 
quality 
Prolonged or 
repetitive seizures or 
difficult to control 
Syncope (not 
associated with a  
procedure) 
NA 
Present 
NA 
NA 
Vertigo 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or respiratory 
failure 
Arthralgia 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or respiratory 
failure 
Bone Mineral Loss 
BMP t-score or z-
score -2.5 to -1.3 
BMP t-score or z-
score <-2.5 
Pathological fracture 
Pathological fracture 
causing life 
threatening 
consequences 
Myalgia 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Disabling causing 
inability to care for 
self or respiratory 
failure 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
APPENDIX 4:  Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 34 of 38 
Osteonecrosis 
NA 
Asymptomatic but 
with radiologic 
findings and no 
surgical intervention 
indicated 
symptomatic with 
radiologic findings or 
surgical intervention 
indicated 
Disabling bone pain 
with radiologic 
findings causing  
inability to care for 
self 
Acute systemic 
allergic reaction 
Localized urticaria 
with no medical 
intervention 
indicated 
Localized urticaria 
with mild 
angioedema with no 
medical intervention 
indicated 
Gen urticaria or 
angioedema with 
medical intervention 
indicated or 
bronchospasm 
Anaphylaxis, 
laryngeal 
angioedema, 
laryngeal edema or 
life-threatening 
bronchospasm 
Chills 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
NA 
Fatigue/malaise 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Incapacitating 
symptoms, unable to 
perform basic self-
care 
Fever 
99.8-101.5 
101.6-102.8 
102.9-104.9 
>104.9 
Pain 
without impact on 
activities 
moderate, with 
impact on activities 
severe, unable to 
perform typical 
activities 
Incapacitating 
symptoms, unable to 
perform basic self-
care 
Unintentional weight 
loss 
NA 
5-9% loss of body 
weight 
10-19% loss of body 
weight 
>19% loss of body 
weight or aggressive 
intervention 
indicated (feeding 
tube, TPN) 
Lipodystrophy or 
lipoatrophy 
detectable by subject 
Detectable by 
provider 
Obvious or disfiguring 
NA 
Diabetes mellitus 
(new onset) 
NA 
without indication for 
medications 
Medications 
indicated 
Life threatening 
consequences 
Diabetes mellitus 
(existing) 
NA 
Requiring 
modification of  
medications 
Lack of control 
despite medication 
modification 
Life threatening 
consequences 
Gynecomastia 
detectable by subject 
Detectable by 
provider 
Obvious or disfiguring 
NA 
Hyperthyroidism 
asymptomatic 
Symptoms causing 
moderate impact of 
activities OR 
medication indicated 
Symptoms causing 
inability to perform 
activities OR 
medication indicated 
 
Life threatening 
consequences 
Hypothyroidism 
asymptomatic 
Symptoms causing 
moderate impact of 
activities OR 
medication indicated 
Symptoms causing 
inability to perform 
activities OR 
uncontrolled despite 
medication 
Life threatening 
consequences 
Intermenstrual 
bleeding 
Spotting 
≤ typical menstrual 
cycle 
≥ typical menstrual 
cycle 
Hemorrhage with life 
threatening 
hypotension 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
APPENDIX 4:  Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 35 of 38 
Urinary obstruction 
(i.e. stone) 
NA 
Without 
hydronephrosis or 
acute kidney injury 
With hydronephrosis 
or acute kidney injury 
Life threatening 
consequences 
Infection (other than 
HIV) 
Localized, no 
systemic 
antimicrobial 
treatment indicated 
AND symptoms 
causing minimal 
impact on activities 
Systemic 
antimicrobial 
treatment indicated 
OR symptoms causing 
>minimal impact on 
activities 
Systemic 
antimicrobial 
treatment indicated 
AND symptoms 
inability to perform 
activities OR 
operation 
intervention 
indicated (beyond 
simple I&D) 
Life threatening 
consequences (i.e. 
septic shock) 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 36 of 38 
APPENDIX 5:  Study Procedure Schedule 
 
Screening/Baseline 
combined visit 
Screening 
(if not same 
day as 
screen) 
Baseline 
(if not same 
day as 
screen) 
1 Month 
4 Month 
Early 
Discontinuation 
Vitals 
X 
X 
X 
X 
X 
X 
MAAS  
X 
X 
 
X 
X 
X 
HIV-SI 
X 
 
X 
X 
X 
X 
History and 
Physical 
X 
X 
 
 
 
 
History and 
Symptom 
based physical 
 
 
X 
X 
X 
X 
Complete 
Blood Count 
X 
 
X 
X 
X 
X 
CD4 panel 
X 
 
X 
X 
X 
X 
Complete 
Metabolic 
Panel 
X 
 
X 
X 
X 
X 
HIV-1 
Quantitative 
viral load 
X 
 
X 
X 
X 
X 
Urinalysis 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
HIV Genotype 
if viral load >200 
copies/mL at last check 
 
if viral load 
>200 
copies/mL 
at last check 
if viral load 
>200 
copies/mL at 
last check 
if viral load 
>200 
copies/mL at 
last check 
if viral load >200 
copies/mL at last 
check 
Urine 
pregnancy 
if indicated 
 
if 
indicated 
if 
indicated 
if 
indicated 
if indicated 
Hepatitis B 
viral load 
if indicated 
 
if 
indicated 
if 
indicated 
if 
indicated 
if indicated 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 37 of 38 
 
APPENDIX 6: Contraindicated Concomitant Medications 
Alpha 1-Adrenoreceptor Antagonist 
alfuzosin  
Antiarrhythmics/Antianginals  
amiodarone, dronedarone, ivabradine, lidocaine 
(systemic)  
Anti-coagulants  
apixaban,rivaroxaban, esclicabazepine  
Anti-convulsants  
carbamezepine, phenobarbital, phenytoin, 
oxcarbazepine  
Anti-gout  
colchicine (in patients with renal and/or hepatic 
impairment)  
Antimycobacterial  
Rifampin,  rifapentine, rifabutin 
Ergot Derivatives 
Such as: dihydroergotamine, ergonovine, 
ergotamine  
Hepatitis C Virus Direct-Acting Antivirals  
elbasvir/grazoprevir , glecaprevir/pibrentasvir, 
simeprevir 
Herbal Products St. 
John’s wort (Hypericum perforatum)  
HMG-CoA Reductase Inhibitors 
lovastatin, simvastatin  
Other Lipid Modifying Agents 
lomitapide  
Inhaled Beta Agonist  
salmeterol  
Neuroleptics 
lurasidone, pimozide 
Opioid Antagonist  
naloxegol  
PDE-5 Inhibitor  
sildenafil (for treatment of pulmonary arterial 
hypertension), avanafil  
Platelet Aggregation Inhibitor  
ticagrelor  
Sedatives/Hypnotics  
triazolam 
Antiplatelet 
ticagrelor 
antineoplastic 
Everoliumus, irinotecan 
antifungals 
voriconazole 
Steroids 
betamethasone, budesonide, ciclesonide, 
dexamethasone, fluticasone, methylprednisolone, 
mometasone, triamcinolone 
 
 
 
 
 
 
 

Symtuza (DRV/COB/FTC/TAF) 
Protocol TMC114FDZHTX4005 
Midland Research Group, Inc. 
 
Version: 0.4 Final  17 Dec 2019 
CONFIDENTIAL 
 Page 38 of 38 
 
APPENDIX 7:  Positive Screen Criteria for Part 2 
 
Positive screen for Part II one positive response in both columns: 
One from below 
One from below 
Question 3 = “Yes” 
Question 8 =  not “always” or “almost always” 
Question 7 = “Yes” 
Question 9 = greater than 2 
Question 11 = “Side effect(s)” 
or named side effect 
Question 10 = greater than 2