Conditions: HIV I Infection
Keywords: switch study dovato biktarvy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 222
Healthy volunteers: no

Brief summary:
Phase 4, randomized, open-label study to evaluate the efficacy, safety and tolerability of switching virologically suppressed adults living with HIV on bictegravir/tenofovir alafenamide/emtricitabine to dolutegravir/lamivudine

Detailed description:
Randomized, open-label, active-controlled study of virologically suppressed participants living with HIV

Participants who provide written informed consent and meet all the eligibility criteria will be randomized in a 2:1 ratio to one of the following 2 treatment groups:

Treatment Group 1 (n=148): FDC of DTG/3TC (50mg/300mg) administered orally, once daily (QD), without regard to food.

Treatment Group 2 (n=74): Stay on baseline regimen consisting of FDC of B/F/TAF (50mg/200mg/ 25mg) (taken as prescribed) without regard to food.

Randomization will be stratified by gender and race at entry given that this study aims to enroll at least 30% of participants who are female and African American.

All participants will be responsible for using their insurance plan to obtain coverage for DTG/3TC and or B/F/TAF, in addition to any labs required by the study. This expectation is clearly outlined in the informed consent. The study team will work with participants to minimize their co-pays for study medications and labs through the use of manufacturer and other external assistance programs.

Study duration will be 48 weeks.

Number of participants planned: Approximately 222 participants

Target Population: HIV-1 infected adult participants who are virologically suppressed (HIV-1 RNA\<50 copies/mL) on FDC of B/F/TAF (50mg/200mg/ 25mg) ≥ 3 months prior to screening

Arms:
arm 1: Treatment Group 1 (n=148): FDC of DTG/3TC (50mg/300mg) administered orally, once daily (QD), without regard to food. arm 2: Treatment Group 2 (n=74): Stay on baseline regimen consisting of FDC of B/F/TAF (50mg/200mg/ 25mg) (taken as prescribed) without regard to food.

Interventions: intervention 1: Dolutegravir / Lamivudine Pill intervention 2: Bictegravir / Emtricitabine / Tenofovir Alafenamide Pill
Intervention descriptions: intervention 1: Experimental intervention 2: Active comparator

Protocol document:
Prot_SAP_000.pdf: 
Orlando Immunology Center (OIC)_008 
 
CONFIDENTIAL 
 
1 
 
 
 
Orlando Immunology Center 
Clinical Protocol 
 
Efficacy, safety and tolerability of switching to 
dolutegravir/lamivudine in virologically-suppressed adults living with 
HIV on bictegravir/tenofovir alafenamide/emtricitabine-the DYAD 
study 
 
 
 
Protocol OIC_008; a prospective randomized clinical trial 
 
 
July 29th 2020 
 
Sponsor: Orlando Immunology Center 
GCP Compliance: This study will be conducted in compliance with Good Clinical 
Practice, and applicable regulatory requirements 
 
 
 


Orlando Immunology Center (OIC)_008 
 
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Investigator Protocol Agreement Page 
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment. 
 
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study. 
 
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
 
____________________________________________________________ 
Signature 
 
Principal Investigator 
 
 
 
 
 
 
Charlotte-Paige Rolle, MD MPH  
 
 
 
 
Director of Research Operations 
Orlando Immunology Center  
1707 North Mills Avenue 
Orlando, FL 32803 
Telephone: 407-647-3960 ext 2158 
Email: crolle@oicorlando.com 
 
 
______________________________________________________________ 
Signature 
 
Co-Investigator 
Edwin Dejesus, MD 
Medical Director 
Orlando Immunology Center  
1707 North Mills Avenue 
Orlando, FL 32803 
Telephone: 407-647-3960 ext 2107 
Email: edejesus@oicorlando.com 
 
Clinical Trials.gov Identifier: NCT 04585737 
 


Orlando Immunology Center (OIC)_008 
 
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Table of Contents 
1. Protocol synopsis for Study OIC_008 
 
 
 
 
6 
 
2. Background information and study rationale 
 
 
 
10 
 
3. Objectives and Endpoints 
 
 
 
 
 
12 
 
4. Study Design 
 
 
 
 
 
 
 
14 
a. Overall Design 
 
 
 
 
 
 
14 
 
b. Treatment Arms and Duration 
 
 
 
 
15 
c. Type and Number of Subjects 
 
 
 
 
15 
 
d. Dose Justification 
 
 
 
 
 
 
15 
e. Benefit:Risk Assessment  
 
 
 
 
 
15 
 
5. Selection of Study Population and Withdrawal Criteria  
 
19  
a. Inclusion Criteria 
 
 
 
 
 
 
19 
b. Exclusion Criteria 
 
 
 
 
 
 
20 
c. Screening Failures  
 
 
 
 
 
22 
d. Withdrawal and Stopping Criteria 
 
 
 
 
23 
e. Subject and Study Completion 
 
 
 
 
29 
 
6. Study Treatment 
 
 
 
 
 
 
30 
a. Investigational Product and Other Study Treatment  
 
30 
b. Protocol-Permitted Substitutions 
 
 
 
 
30 
c. Treatment Assignment 
 
 
 
 
 
30 
d. Planned Dose adjustments  
 
 
 
 
31  
e. Blinding 
 
 
 
 
 
 
 
31 
f. Packaging and Labeling 
 
 
 
 
 
31 
g. Preparation/Handling/Storage/Accountability 
 
 
31 
 


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h. Compliance with study treatment Administration 
 
 
31 
i. 
Treatment after the end of the study 
 
 
 
31 
j. 
Prior and Concomitant Medications  
 
 
 
31 
 
7. Study Procedures 
 
 
 
 
 
 
34 
a. Participant enrollment and treatment assignment 
 
 
34 
b. Pretreatment Assessments  
 
 
 
 
34 
c. Day 1 Assessments  
 
 
 
 
 
35 
d. Treatment Assessments (W4-48) 
 
 
 
 
35 
e. Clinical Laboratory Assessments 
 
 
 
 
36 
f. Assessments for Premature Discontinuation from Study 
 
38 
g. End of Study 
 
 
 
 
 
 
38 
h. Post Study Care 
 
 
 
 
 
 
38 
i. 
Management of virologic rebound  
 
 
 
38 
 
 
8. Safety  
 
 
 
 
 
 
 
39 
a. Adverse Events (AEs) and Serious Adverse Events (SAEs) 
 
39 
b. Time period and frequency of collecting AE and SAE information 
40 
 
c. Method of detecting AEs and SAEs  
 
 
 
41 
d. Follow up of AEs and SAE 
 
 
 
 
 
41 
e. Reporting requirements for AEs and SAEs 
 
 
 
41 
f. Pregnancy  
 
 
 
 
 
 
41 
g. Physical Exams 
 
 
 
 
 
 
42 
h. Vital Signs  
 
 
 
 
 
 
42 
i. 
Clinical Safety Laboratory Assessments 
 
 
 
42 
 
j. 
Toxicity Management 
 
 
 
 
 
43 
 
9. Data Management 
 
 
 
 
 
 
48 
 


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10. Statistical Considerations and Data Analyses 
 
 
 
49 
a. Analysis Objectives 
 
 
 
 
 
 
49 
b. Demographic Data and Baseline Characteristics 
 
 
49 
c. Efficacy Analysis 
 
 
 
 
 
 
50 
d. Safety Analysis 
 
 
 
 
 
 
50 
e. Patient Reported Outcomes (PROs) 
 
 
 
 
51 
f. Sample size calculation 
 
 
 
 
 
51 
g. Analysis Schedule 
 
 
 
 
 
 
51 
 
11. Study Governance and Considerations  
 
 
 
52 
a. Posting of Information on Publicly Available Clinical Trial Registers 
52 
 
 
b. Regulatory and Ethical Considerations, Including the Informed  
52 
 
 
Consent Process 
 
 
 
c. Quality Control (Study Monitoring) 
 
 
 
 
52 
 
 
 
d. Quality Assurance 
 
 
 
 
 
 
53 
 
 
 
e. Study and Site Closure 
 
 
 
 
 
53 
 
 
 
f. Records Retention 
 
 
 
 
 
 
53 
 
 
 
 
g. Provision of Study Results, Posting of Information on Publicly   
54 
 
 
Available Clinical Trials Registers and Publication 
 
12. References 
 
 
 
 
 
 
 
55 
 
13. Appendices 
 
 
 
 
 
 
 
57 
Appendix 1. Study Procedures Table 
 
 
 
 
57 
 
 
Appendix 2. Pregnancy Precautions, Definition for Persons of  
 
58 
 
 
 
Childbearing Potential, and Contraceptive Requirements  
 
 
 
 


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1. Protocol Synopsis for OIC_008 
 
Orlando Immunology Center 
1707 N. Mills Avenue 
Orlando, FL 32803 
 
 
Study Title: Efficacy, safety and tolerability of switching to dolutegravir/lamivudine in virologically-
suppressed adults living with HIV on bictegravir/tenofovir alafenamide/emtricitabine-the DYAD study 
ClinicalTrials.gov Identifier: TBD 
Study Centers planned: Orlando Immunology Center 
Objectives: 
The primary objective of this study is: 
• 
to evaluate the efficacy of switching from B/F/TAF to DTG/3TC versus continuing the baseline 
regimen of B/F/TAF in HIV-infected, virologically suppressed adults as determined by the 
proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48  
 
The secondary objectives of this study are to:  
• 
to evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion 
of participants with HIV-1 RNA≥ 50 copies/mL at Weeks 12 and 24 
• 
to evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion 
of participants with HIV-1 RNA<50 copies/mL at Weeks 12, 24 and 48 
• 
to evaluate the safety, and tolerability of switching to DTG/3TC from B/F/TAF in HIV-infected, 
virologically suppressed adults through Week 48 
 
Study Design: 
Randomized, open-label, active-controlled study of virologically suppressed participants living with HIV 
Participants who provide written informed consent and meet all the eligibility criteria will be 
randomized in a 2:1 ratio to one of the following 2 treatment groups:  
Treatment Group 1 (n=148): FDC of DTG/3TC (50mg/300mg) administered orally, once daily (QD), 
without regard to food.  
Treatment Group 2 (n=74): Stay on baseline regimen consisting of FDC of B/F/TAF (50mg/200mg/ 25mg) 
(taken as prescribed) without regard to food. 


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Randomization will be stratified by gender and race at entry given that this study aims to enroll at least 
30% of participants who are female and African American. 
All participants will be responsible for using their insurance plan to obtain coverage for DTG/3TC and or 
B/F/TAF, in addition to any labs required by the study.  This expectation is clearly outlined in the 
informed consent.  The study team will work with participants to minimize their co-pays for study 
medications and labs through the use of manufacturer and other external assistance programs. 
Study duration will be 48 weeks. 
Number of participants planned:  Approximately 222 participants 
Target Population:  HIV-1 infected adult participants who are virologically suppressed (HIV-1 RNA<50 
copies/mL) on FDC of B/F/TAF (50mg/200mg/ 25mg) ≥ 3 months prior to screening   
Duration of Treatment:   
After screening, eligible participants will be treated for at least 48 weeks. Following the Screening and 
Day 1 visits, participants will be required to return for study visits at Weeks 4, 12, 24, and 48.  There are 
planned participant phone follow-up visits at Weeks 1 and 36. Participants who complete the study 
through the Week 48 visit will be referred  back to their regular HIV clinic provider for routine follow-up 
upon study completion. 
Diagnosis and Main Eligibility Criteria: 
Participants must meet all of the following inclusion criteria to be eligible to participate in the study. 
Eligible participants with chronic hepatitis B infection or chronic hepatitis C infection who are 
anticipated to need HCV therapy during the study period are not permitted to enroll.  Other main 
inclusion/exclusion criteria are: 
• 
Currently receiving the FDC of B/F/TAF for ≥ 3 months  
• 
Documented plasma HIV-1 RNA < 50 copies/mL x2 during treatment with B/F/TAF at least 3 
months apart prior to the enrollment visit (second HIV-1 RNA may be value from the screening 
visit) 
• 
Have no history of virologic failure of any prior regimen 
• 
Have a stable insurance plan that is not expected to change in the next 48 weeks 
• 
Have no documented or suspected resistance to INSTIs  
• 
History of 1-2 thymidine analogue mutations (TAMs), and other RT substitutions are allowed, 
with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, 
and K219Q/E/N/R), M184V/I, T69-insertions, or K65R/E/N in RT will be excluded 
• 
Estimated glomerular filtration rate (eGFR) ≥50mL/min according to the Cockcroft-Gault 
formula for creatinine clearance 
• 
Medically stable without an acute or chronic illness deemed by the investigator to limit the 
subject’s ability to participate and complete the study  


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Study Procedures/Frequency: 
After Screening procedures, eligible participants will be randomized 2:1 to Treatment Group 1 or 
Treatment Group 2 and treated for 48 weeks.  Following the Day 1 visit, participants will be required to 
return for study visits at Weeks 4, 12, 24, and 48.  There are planned participant phone follow-up visits 
at Weeks 1 and 36.  Laboratory analyses (chemistry, hematology, and urinalysis), HIV-1 RNA, CD4+ cell 
count, assessment of adverse events and concomitant medications, and complete or symptom directed 
physical examinations will be performed at Screening, Day 1 and subsequent study visits.  Whole blood 
for HIV-1 DNA archive testing will be collected at Screening for all participants.  Historical HIV-1 RNA 
genotypes will be collected if available. 
Test Product, Dose, and Mode of Administration: 
FDC of dolutegravir 50 mg / lamivudine 300 mg (DTG/3TC) administered orally, once daily, without 
regard to food 
Reference Therapy, Dose, and Mode of Administration: 
Baseline regimen consisting of FDC of bictegravir 50 mg / emtricitabine 200 mg / tenofovir alafenamide 
25mg (B/F/TAF) taken as prescribed 
Criteria for Evaluation:  
Efficacy:  
The primary efficacy endpoint is:  
• 
The proportion of participants with HIV-1 RNA≥50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm  
The secondary efficacy endpoints are: 
• 
The proportion of participants with HIV-1 RNA ≥50 copies/mL at Weeks 12 and 24 as defined by 
the US FDA-defined snapshot algorithm 
• 
The proportion of participants with HIV-1 RNA <50 copies/mL at Weeks 12, 24 as defined by the 
US FDA-defined snapshot algorithm 
• 
The change from baseline in CD4+ cell count and CD4+/CD8+ ratio at Weeks 12, 24 and 48 
Safety: Adverse events, clinical laboratory tests, and tolerability of treatment regimens 
Patient Reported Outcomes: 
HIV Symptoms Distress Module Index (HIV-SI) will be administered at Day 1, Weeks 4, 12, 24, and 48.  
HIV Treatment Satisfaction Questionnaire Status (HIV-TSQs) will be administered at Day 1 and HIV 
Treatment Satisfaction Questionnaire Change (HIV-TSQc) will be administered at Weeks 4 and Week 24. 
Visual Analogue Scale (VAS) Adherence Questionnaire will be administered at Day 1 and at all visits 
through Week 48.   
Statistical Methods:  


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The primary analysis will consist of a non-inferiority test of switching to the FDC of DTG/3TC versus 
staying on B/F/TAF with respect to the proportion of participants with HIV-1 RNA ≥50 copies/mL at 
Week 48, as defined by the US FDA-defined snapshot algorithm. It will be concluded that FDC of 
DTG/3TC is non-inferior to B/F/TAF if the upper bound of the 2-sided 95% confidence interval (CI) of the 
difference between treatment groups [DTG/3TC –B/F/TAF] in the percentage of participants with HIV-1 
RNA≥ 50 copies/mL is less than 6% (i.e., a margin of 6% is applied to the non-inferiority assessment). The 
2-sided 95% CIs will be constructed based on the exact method.  
The proportion of participants with HIV-1 RNA ≥50 copies/mL at Weeks 12, and 24, and the proportion 
of participants with HIV-1 RNA <50 copies/mL at Weeks 12, 24 and 48 as defined by the US FDA-defined 
snapshot algorithm will also be summarized. The 95% CIs at Weeks 12 and 24 will be constructed in the 
same manner as described for the primary efficacy endpoint.  
The change from baseline in CD4+ cell count and CD4+/CD8+ ratio at Weeks 12, 24 and 48 will be 
summarized by treatment using descriptive statistics. The differences and the associated 95% CIs at 
Week 48 will be constructed using an Analysis of Variance (ANOVA) model, including treatment 
(DTG/3TC vs. B/F/TAF).   
Adverse events and clinical laboratory assessments will be summarized using descriptive statistics.  
Sample sizes of 148 in the DTG/3TC FDC and 74 in B/F/TAF FDC group achieve approximately 80% power 
to detect a non-inferiority margin difference between the group proportions of 0.06 for HIV-1 RNA≥50 
copies/mL at Week 48. The power is computed for the case when the actual treatment group difference 
is zero (treatment = reference). The test statistic used is the one-sided Score test (Farrington & 
Manning) with the significance level of 0.025. 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2. Background Information and study rationale 
DTG/3TC which is FDA-approved as the co-formulated single tablet regimen (STR), Dovato™ is currently 
approved for the treatment of HIV-1 infection in treatment-naïve adults.  This is based on 48-week data 
from the pooled Gemini 1&2 studies which demonstrated a non-inferior virologic suppression rate of 
91% in patients receiving DTG/3TC vs. 93% in patients receiving DTG+TDF/FTC [1].  There was no 
evidence of treatment-emergent resistance in either arm among confirmed virologic withdrawals. More 
recently, 96-week data have been reported which confirm the durability of virologic suppression and 
high genetic barrier to resistance with this 2-drug (2DR) regimen vs. the 3-drug (3DR) comparator [2].  
Additional data from these studies reveal a lower frequency of drug-related adverse events (AEs) and an 
improved safety profile with respect to renal and bone biomarkers in the 2DR arm [1, 2].  This suggests 
that DTG/3TC may have an advantage with respect to both short and long-term toxicities in comparison 
to traditional 3DRs while preserving virologic efficacy and barrier to resistance. 
Early data from observational studies evaluating the efficacy and safety of switching virologically 
suppressed adults to DTG/3TC demonstrated virologic suppression rates of 82-97% at Week 48 in the 
2DR arm [3-5].  Recently, long-term data from an Italian cohort of 566 patients switched from a variety 
of regimens to DTG/3TC revealed probabilities of maintaining virologic suppression at Weeks 96 and 144 
of 97.5% and 96.5% respectively [6].  Patients in the 2DR also experienced significant increases in CD4+ 
count and HDL cholesterol and, significant decreases in total cholesterol and triglycerides.  Other 
observational data demonstrates similar safety findings with several studies also revealing significant 
increases in CD4+ count [7, 8] and improved lipid profiles [5, 7, 8] in those switched to DTG/3TC from 
other antiretroviral regimens. 
Recently, data from a large randomized controlled trial (TANGO) evaluating the efficacy and safety of 
switching virologically suppressed adults on TAF-based regimens to DTG/3TC reported virologic 
suppression rates of 93% at Week 48 in both those switched to the 2DR vs. those who remained on their 
TAF-based regimen [9].  No patients treated with DTG/3TC experienced confirmed virologic withdrawal 
and there were no significant changes in lipids, AEs and tolerability between treatment arms [9].  
Baseline demographics revealed only 7-9% of trial participants were women and only 14-16% were 
African American or of African heritage [9].  This study also did not enroll patients on B/F/TAF 
(Biktarvy™), which is currently the most commonly prescribed guideline recommended single tablet 
regimen in ARV-experienced patients.  Registrational studies of B/F/TAF demonstrated non-inferiority to 
its comparators in virologically suppressed adults [10, 11] with reports of less bothersome symptoms in 
patients receiving B/F/TAF compared to those receiving ABC/3TC/DTG [12].  To date, there are no 
studies evaluating the efficacy and safety of switching patients from B/F/TAF to DTG/3TC, and DTG/3TC 
does not currently have an FDA indication for use in treatment-experienced patients living with HIV. 
Further data would be useful to evaluate the efficacy and safety of switching from a 3DR STR to a 2DR 
STR given the lack of FDA indication for the use of DTG/3TC in treatment-experienced patients living 
with HIV infection.  The need for more information on this switch strategy in certain subgroups i.e. 
African Americans and females would also be valuable given that these populations are often under-
represented in clinical trials of novel HIV therapeutics and are disproportionately affected by the HIV 
epidemic in the United States. 


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The DYAD study is a randomized, open-label, prospective switch study to evaluate the efficacy and 
safety of switching virologically suppressed adults living with HIV on B/F/TAF to DTG/3TC vs. remaining 
on B/F/TAF through 48 weeks of treatment.  This trial will also have a requirement for 30% of 
participants to be female and 30% of participants to be from communities of color (Black or 
Hispanic/Latino). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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3. Objectives and Endpoints 
Objective 
Endpoint 
Primary 
To demonstrate the non-inferior antiviral 
activity of switching to DTG/3TC once daily 
compared to continuation of B/F/TAF over 48 
weeks in HIV-1 infected, virologically 
suppressed subjects 
Virologic failure endpoint as per FDA snapshot 
category at Week 48 
Secondary 
To demonstrate the antiviral activity of 
switching to DTG/3TC once daily compared to 
continuation of B/F/TAF over 48 weeks 
Proportion of patients with HIV-1 RNA ≥50 
copies/mL at Weeks 12 and 24  
 
Proportion of patients with HIV-1 RNA<50 
copies/mL at Weeks 12, 24 and 48 
To evaluate the immune effects of DTG/3TC 
once daily compared to continuation of 
B/F/TAF over 12, 24, and 48 weeks 
Change from Baseline in CD4+ cell count and in 
CD4+/CD8+ cell count ratio at Weeks 12, 24 and 
48 
To evaluate the safety and tolerability of 
DTG/3TC once daily compared to B/F/TAF over 
time 
Incidence and severity of AEs and laboratory 
abnormalities through 48 weeks 
 
Proportion of subjects who discontinue 
treatment due to AEs through 48 weeks 
To evaluate the effects of DTG/3TC once daily 
on fasting lipids over time compared to TBR 
Change from Baseline in fasting lipids at Weeks 
24, and 48 
To evaluate changes in weight, waist 
circumference and BMI in those treated with 
DTG/3TC vs. B/F/TAF over time 
 
Change from Baseline in weight, waist 
circumference and BMI at Weeks 12, 24, and 48 
To assess health related quality of life for 
subjects treated with DTG/3TC compared to 
B/F/TAF over time 
Change from Baseline in health status using the 
HIV-SI at Weeks 4, 12, 24 and 48 (or Withdrawal 
from the study) 
To assess treatment satisfaction in subjects 
treated with DTG/3TC compared to B/F/TAF 
over time 
Change from baseline in treatment satisfaction 
using the HIV TSQs at Weeks 4, and 24 (or 
withdrawal from the study 
To assess viral resistance in subjects meeting 
Virologic Rebound Criteria 
Incidence of observed genotypic resistance to 
ARVs for subjects meeting Virologic Rebound 
Criteria 
Exploratory 
To evaluate the effect of patient characteristics 
(e.g., demographic factors, Baseline CD4) on 
• 
Proportion of subjects by subgroup(s) 
(e.g., by age, gender, Baseline CD4) with 


Orlando Immunology Center (OIC)_008 
 
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antiviral and immunological responses to 
DTG/3TC compared to B/F/TAF 
plasma HIV-1 RNA ≥50 c/mL using the 
Snapshot algorithm at Weeks 12, 24, 
and 48 
• 
Change from Baseline in CD4+ cell 
counts at Weeks 12, 24, and 48, by 
patient subgroups 
To assess willingness to switch for subjects 
treated with DTG/3TC compared to B/F/TAF 
Reasons for Willingness to Switch at Day 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. Study Design 
a. Overall Design 
This is a 48-week, randomized, open-label, active-controlled, parallel-group study to assess antiviral 
activity, safety and tolerability of replacing B/F/TAF with a two-drug regimen of DTG/3TC in virologically 
suppressed adults living with HIV who are stable on B/F/TAF.  The study will include a Screening Phase 
(up to 42 days), and a Switch Phase (Day 1 up to Week 48).  Approximately 222 HIV-1 infected adults 
who are on B/F/TAF will be randomized 2:1 to switch to DTG/3TC once daily (DTG/3TC arm) for up to 48 
weeks, or to continue B/F/TAF for 48 weeks. All participants will be responsible for using their insurance 
plan to obtain coverage for DTG/3TC and or B/F/TAF, in addition to any labs required by the study.  This 
expectation is clearly outlined in the informed consent.  The study team will work with participants to 
minimize their co-pays for study medications and labs through the use of manufacturer and other 
external assistance programs.   
The primary endpoint for the study is the proportion of participants who maintain virologic suppression 
(defined as an HIV-1 RNA<50 copies/mL) at Week 48 per the FDA snapshot algorithm.  The Week 48 
primary analysis will take place after the last subject has had their Week 48 viral load assessed, including 
any retests. All subjects who successfully complete 48 weeks of treatment will complete the study and 
be referred back to their regular HIV clinic provider for routine management and decisions regarding 
ARV (antiretroviral) therapy. 
No dose reductions, modifications, or changes in the frequency of any components of each regimen will 
be allowed during this study.  Adherence to the study protocol, including those specified in the Study 
Procedures Table (Appendix 1), are essential and required for study conduct.  If deviations are required 
for the management of immediate safety concerns, these will be communicated promptly to the study 
PI and any regulatory authorities as appropriate. 
 
 
 
 


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b. Treatment Arms and Duration 
Screening Period (Up to 42 days) 
Randomization may occur as soon as all screening procedures and entry criteria data are confirmed and 
available on file at the site.  The Screening period of up to 42 days is to allow receipt of all screening 
assessment results, to enable source document verification of entry criteria and to accommodate 
scheduling. 
Randomized Switch Phase (Day 1 to Week 48) 
Subjects who fulfill all eligibility requirements will be randomly assigned 2:1 to receive DTG/3TC FDC 
once daily up to Week 48 or continue B/F/TAF up to Week 48.  The DTG/3TC and B/F/TAF will be 
administered in an open-label fashion throughout the study. All participants will be responsible for using 
their insurance plan to obtain coverage for DTG/3TC and or B/F/TAF, in addition to any labs required by 
the study. The primary analysis will take place after the last subject completes up to 52 weeks on 
therapy, to allow for the collection of a confirmatory viral load measurement in subjects presenting with 
HIV-1 RNA ≥50 c/mL at the Week 48 visit.  If the retest HIV-1 RNA is <50 c/mL, then the subject will be 
considered to have met the criteria for virologic responder by the Food Drugs and Administration 
(FDA)’s Snapshot algorithm at Week 48.  If the retest HIV-1 RNA is ≥50 c/mL, then the subject will be 
considered to be a virologic failure at Week 48 by Snapshot.  The secondary analysis at Weeks 12 and 24 
will take place after the last subject completes up to 16 and 28 weeks on therapy respectively, as 
needed, to allow for the collection of a confirmatory viral load measurement in subjects presenting with 
HIV-1 RNA ≥50 c/mL at Weeks 12 and 24.  At the end of the study at Week 48, subjects will referred back 
to their regular HIV clinic provider for routine management and decisions regarding ARV (antiretroviral) 
therapy.   
c. Type and Number of Subjects 
The target population to be enrolled is HIV-1 infected adults who are virologically suppressed on 
B/F/TAF with no evidence or history of ARV drug-resistance affecting dolutegravir or lamivudine.   
 
Assuming a 15% screen failure rate, approximately 260 HIV-1-infected adult subjects will be screened to 
achieve 222 randomized subjects for a total of 148 evaluable subjects in Treatment group 1 (DTG/3TC 
FDC) and 74 evaluable subjects in Treatment group 2 (B/F/TAF FDC).   
 
d. Dose Justification 
The DTG/3TC FDC containing DTG (50 mg) and 3TC (300 mg) has been approved by the US-FDA for use 
once daily for the treatment of human immunodeficiency virus type1 (HIV-1) infection in adults.   
 
e. Benefit:Risk Assessment 
 
All patients with HIV-1 infection should receive effective antiretroviral therapy. Potential risks associated 
with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and lactic acidosis with 
steatosis [13].  The risk of class effects is considered to be low. Potential benefits may include provision 


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of a new ARV therapy which may have fewer side effects and drug-drug interactions than alternative 
therapies resulting in improved adherence and long-term virologic suppression. Other potential benefits 
include the knowledge that patient participation will contribute to the body of knowledge of HIV 
therapies in African American and female patients.  In phase 3 studies of DTG/3TC, the subgroup of 
participants self-identified as Black or African American had similar outcomes for efficacy and safety 
compared with the study population as a whole.  The overall benefit-risk assessment for DTG/3TC is 
favorable at this time.  
Summaries of findings from both clinical and non-clinical studies conducted with DTG or 3TC can be 
found in the product labels.   
The following section outlines the risk assessment and mitigation strategy for DTG and 3TC in this 
protocol.  For B/F/TAF, please consult the prescribing label for further information on the potential risks 
and benefits associated with use [18]. 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) [DTG/3TC] Refer to Product Label for additional information 
DTG: Hypersensitivity reaction 
(HSR) and rash 
DTG: HSR has been observed uncommonly 
with DTG.  Rash was commonly reported in 
DTG Phase IIb/III clinical trials; episodes were 
generally mild to moderate in intensity; no 
episodes of severe rash, such as Stevens-
Johnson Syndrome (SJS), Toxic Epidermal 
Necrolysis (TEN) and erythema multiforme 
were reported. 
Subjects with history of 
allergy/sensitivity to any of the study 
drugs are excluded.  
Toxicity management for rash will be 
left to the discretion of the investigator 
but specific guidance depending on 
severity is included in Section 8j. 
 The subject informed consent form 
(ICF) includes information on this risk 
and the actions subjects should take in 
the event of a HSR or associated signs 
and symptoms 
DTG: Drug induced liver injury 
(DILI) and other clinically 
significant liver chemistry 
elevations 
3TC: Use in HBV coinfected 
patients and emergence of HBV 
variants resistant to 3TC 
DTG: Non-clinical data suggested a possible, 
albeit low, risk for hepatobiliary toxicity with 
DTG.  Drug-related hepatitis is considered an 
uncommon risk for ART containing DTG 
regardless of dose or treatment population.  
For subjects with hepatitis B virus (HBV) 
and/or hepatitis C virus (HCV) co-infection, 
improvements in immunosuppression as a 
result of HIV virologic and immunologic 
responses to DTG-containing ART, along with 
inadequate therapy for HBV co-infected 
subjects, likely contributed to significant 
elevations in liver chemistries.   
Subjects meeting any of the following 
criteria during the screening period are 
excluded from participating. 
• 
Alanine aminotransferase 
(ALT) ≥5 times the upper limit 
of normal (ULN) or ALT 
≥3xULN and bilirubin ≥1.5x 
ULN (with >35% direct 
bilirubin) 
• 
Subjects positive for Hepatitis 
B surface antigen (+HBsAg) 
• 
 Subjects negative for HBsAg 
and anti-HBsAg and positive 
for anti-HBc and HBV DNA. 


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There have been rare post-marketing reports 
of acute hepatic failure in association with 
DTG-containing regimens 
3TC:  Current treatment guidelines [13] do not 
recommend monotherapy with 3TC for 
patients with HBV infection, which is what 
subjects randomised to DTG plus 3TC, would 
effectively be receiving.  Emergence of HBV 
variants associated with resistance to 3TC has 
been reported in HIV-1 infected patients who 
have received 3TC-containing antiretroviral 
regimens in the presence of concurrent 
infection with HBV.  Additionally, 
discontinuation of 3TC in HBV co-infected 
subjects can result in severe exacerbations of 
hepatitis B 
• 
 Anticipated need for any 
hepatitis C virus (HCV) 
therapy during the first 48 
weeks of the study, and for 
HCV therapy based on 
interferon or for any drugs 
that have a potential for 
adverse drug-drug 
interactions with study 
treatment throughout the 
entire study period.  
Toxicity management for elevations in 
liver enzymes will be left to the 
discretion of the investigator but 
specific guidance depending on 
severity is included in Section 8j. 
DTG: Psychiatric disorders 
DTG: Psychiatric disorders including suicidal 
ideation and behaviors are common in HIV-
infected patients. Events of suicidal ideation, 
attempt, behaviour and completion were 
observed in clinical studies of DTG, primarily 
in subjects with a pre-existing history of 
depression or other psychiatric illness. The 
psychiatric profile for DTG (including 
suicidality, depression, bipolar and 
hypomania, anxiety and abnormal dreams) 
was similar to RAL-or favorable compared 
with EFV-based regimens.  
The reporting rate for insomnia was 
statistically higher for blinded DTG+ 
abacavir/lamivudine (ABC/3TC) compared to 
EFV/TDF/FTC in ING114467; however, this 
was not duplicated in any other Phase IIb/III 
study conducted with DTG.   
Subjects who in the investigator’s 
judgment, pose a significant suicidality 
risk, are excluded from participating. 
Because of the elevated risk in the HIV-
infected population, treatment 
emergent assessment of suicidality will 
be monitored during this study through 
the end of the continuation phase.     
Investigators are advised to consider 
mental health consultation or referral 
for subjects who experience signs of 
suicidal ideation or behaviour (See 
Section 8k).  
The subject informed consent form 
includes information on the risk of 
depression and suicidal ideation and 
behavior.     
DTG: Theoretical serious drug 
interaction with dofetilide and 
fampridine/dalfampridine 
DTG should not be used with products with 
narrow therapeutic windows, that are 
substrates of organic cation transporter 2 
(OCT2), including but not limited to the 
antiarrhythmic agent dofetilide, or the 
potassium channel blocker fampridine (also 
known as dalfampridine), due to the potential 
risk of serious or life-threatening toxicity. 
The co-administration of DTG with 
dofetilide or fampridine 
(dalfampridine) is prohibited in the 
study (Section 6j). 
DTG and 3TC: Renal function 
DTG:  Mild elevations of creatinine have been 
observed with DTG which are related to a 
likely benign effect on creatinine secretion 
with blockade of OCT-2.  DTG has been shown 
to have no significant effect on glomerular 
filtration rate (GFR) or effective renal plasma 
flow.  
Toxicity management for declines in 
renal function will be left to the 
discretion of the investigator but 
specific guidance depending on 
severity is included in Section 8j. 
Creatinine clearance is calculated in all 
patients prior to initiating therapy and 
renal function (creatinine clearance 


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3TC:  3TC is eliminated by renal excretion and 
exposures increase in patients with renal 
dysfunction. 
and serum phosphate) will be 
monitored at all subsequent study 
visits.  
 
Subjects with creatinine clearance <50 
mL/min are excluded from 
participation in this study. 
DTG: Creatine Phosphokinase 
(CPK) elevations 
Asymptomatic CPK elevations mainly in 
association with exercise have been reported 
with DTG therapy. 
Toxicity management for elevations in 
CPK will be left to the discretion of the 
investigator but specific guidance 
depending on severity is included in 
Section 8j. 
 
DTG: Neural tube defects 
In one ongoing birth outcome surveillance 
study in Botswana, early results from an 
unplanned interim analysis show that 5/1683 
(0.3%) of women who were taking DTG when 
they became pregnant had babies with neural 
tube defects compared to a background rate 
of 0.1%. 
1. A female subject is eligible to 
participate if she is not pregnant, not 
lactating, and, if she is a female of 
reproductive potential, agrees to 
follow one of the options listed in the 
Modified List of Highly Effective 
Methods for Avoiding Pregnancy in 
Females of Reproductive Potential 
(FRP) (see Appendix 2) from 30 days 
prior to the first dose of study 
medication and for at least 2 weeks 
after the last dose of study medication. 
 2. Women who are breastfeeding or 
plan to become pregnant or breastfeed 
during the study are excluded.  
3. Women who become pregnant, or 
who desire to be pregnant while in the 
study, or who state they no longer are 
willing to comply with the approved 
pregnancy avoidance methods, will 
have study treatment discontinued and 
will be withdrawn from the study.  
4. Females of reproductive potential 
are reminded re: pregnancy avoidance 
and adherence to contraception 
requirements at every study visit.  
5. Pregnancy status is monitored at 
every study visit 
  
 
 


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5. Selection of Study Population and Withdrawal Criteria 
Specific information regarding warnings, precautions, contraindications, adverse events, and other 
pertinent information on the study medication that may impact subject eligibility is provided in the 
Product Insert for DTG/3TC (Dovato™) [14].   
 
Deviations from inclusion and exclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to 
the criteria as specified in the protocol is essential.  
 
The following are study specific eligibility criteria unless stated otherwise. In addition to these criteria, 
investigators must exercise clinical discretion regarding selection of appropriate study subjects, taking 
into consideration any local treatment practices or guidelines and good clinical practice (GCP). 
 
a. Inclusion Criteria 
Eligible subjects must:  
• 
be able to understand and comply with protocol requirements, instructions, and restrictions 
• 
be likely to complete the study as planned 
• 
be considered appropriate candidates for participation in an investigative clinical trial with 
medication (e.g. no active substance abuse, acute major organ disease, or planned long-term 
work assignments out of the country).   
A subject will be eligible for inclusion in this study only if all of the following criteria apply: 
AGE 
1. Aged 18 years or older at the time of signing the informed consent 
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 
2. HIV-1 infected men or women.  
3. Must have a stable form of insurance that is expected to continue without significant changes for at 
least 48 weeks 
4. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL at least 3 months 
apart prior to Day 1 (the screening HIV-1 RNA can count as the second measurement) 
5. Plasma HIV-1 RNA <50 c/mL at Screening.  
6. Must be on uninterrupted B/F/TAF for at least 3 months prior to screening 
SEX 
7. Male or female 


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A female subject is eligible to participate if she is not pregnant [as confirmed by a negative serum 
human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Day 
1/Randomization (a local serum hCG test at Randomization is allowed if it can be done, and results 
obtained, within 24 hours prior to randomization)], not lactating, and at least one of the following 
conditions applies:  
a. Non-reproductive potential defined as:  
• 
Pre-menopausal females with one of the following:  
o Documented tubal ligation  
o Documented hysteroscopic tubal occlusion procedure with follow-up confirmation 
of bilateral tubal occlusion  
o Hysterectomy  
o Documented Bilateral Oophorectomy  
• 
Post-menopausal defined as 12 months of spontaneous amenorrhea [in questionable 
cases a blood sample with simultaneous follicle stimulating hormone (FSH) and 
estradiol levels consistent with menopause (refer to laboratory reference ranges for 
confirmatory levels)].  Females on hormone replacement therapy (HRT) and whose 
menopausal status is in doubt will be required to use one of the highly effective 
contraception methods if they wish to continue their HRT during the study.  
Otherwise, they must discontinue HRT to allow confirmation of post-menopausal 
status prior to study enrollment.  
b. Reproductive potential and agrees to follow one of the options listed in the Modified List of 
Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) 
(see Appendix 2) from 30 days prior to the first dose of study medication and for at least 2 
weeks after the last dose of study medication.  
The investigator is responsible for ensuring that subjects understand how to properly use these 
methods of contraception. All subjects participating in the study should be counseled on safer sexual 
practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on 
the risk of HIV transmission to an uninfected partner. 
INFORMED CONSENT 
8. Capable of giving signed informed consent, which includes compliance with the requirements and 
restrictions listed in the consent form and in this protocol.  Eligible subjects must sign a written 
Informed Consent Form before any protocol-specified assessments are conducted 
 
 
b. Exclusion Criteria 
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 


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CONCURRENT CONDITIONS/MEDICAL HISTORY 
1. Women who are breastfeeding or plan to become pregnant or breastfeed during the study.  
2. Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease [15], 
EXCEPT cutaneous Kaposi’s sarcoma not requiring systemic therapy.  Historical or current CD4 cell 
counts less than 200 cells/mm3 are NOT exclusionary.  
3. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification [16].  
4. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, 
hypoalbuminaemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary 
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).   
5. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for 
Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (antiHBc), Hepatitis B surface antigen 
antibody (anti-HBs) and HBV DNA as follows: 
• 
Subjects positive for HBsAg are excluded. 
• 
Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and 
positive for HBV DNA are excluded.   
Note: Subjects positive for anti-HBc (negative HBsAg status) and positive for antiHBs 
(past and/or current evidence) are immune to HBV and are not excluded.  AntiHBc 
must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and NOT anti-HBc 
IgM.  
6. Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study 
 
7. Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear 
documentation of treatment).  Subjects who are at least 7 days post completed treatment are 
eligible.  
 
8. History or presence of allergy or intolerance to the study drugs or their components or drugs of 
their class.  
 
9. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, 
non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.  
10.Subjects who in the investigator’s judgment, poses a significant suicidality risk.   
EXCLUSIONARY TREATMENTS PRIOR TO SCREENING OR DAY 1 
11. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening 
12. Treatment with any of the following agents within 28 days of Screening 
• 
radiation therapy 
• 
cytotoxic chemotherapeutic agents 
• 
any systemic immune suppressant  


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13. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the 
test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to 
the first dose of study medication. 
 
14. Use of any regimen consisting of single or dual ART 
LABORATORY VALUES OR CLINICAL ASSESSMENTS AT SCREENING 
15. Any evidence of major NRTI mutation (defined as history of 3 or more TAMs (M41L, D67N, K70R, 
L210W, T215F/Y, and K219Q/E/N/R), M184V/I, T69-insertions, or K65R/E/N) or presence of any major 
INSTI resistance-associated mutation [17] in any available prior resistance genotype assay test result 
16. Any verified Grade 4 laboratory abnormality 
17. Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN and 
bilirubin ≥1.5xULN (with >35% direct bilirubin).  
18. Creatinine clearance of <50mL/min/1.73m2 via CKD-EPI method. 
EXCLUSIONARY CRITERIA PRIOR TO SCREENING OR DAY 1 
19. Within the 6 to 12-month window prior to Screening and after confirmed suppression to <50 
copies/mL, any plasma HIV-1 RNA measurement >200 c/mL.  
20. Within the 6 to 12-month window prior to Screening and after confirmed suppression to <50 
copies/mL, 2 or more plasma HIV-1 RNA measurements ≥50 c/mL.  
21. Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART 
regimen, any plasma HIV-1 RNA measurement ≥50 copies/mL.  
22. Any drug holiday during the 12 months prior to Screening, except for brief periods (less than 1 
month) where all ART was stopped due to tolerability and/or safety concerns.  
23. Any history of switch to another regimen, defined as change of a single drug or multiple drugs 
simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA ≥400 
copies/mL. 
 
c. Screening Failures 
Screen failures are defined as subjects who consent to participate in the clinical trial but are never 
subsequently randomized.  In order to ensure transparent reporting of screen failure subjects meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, and respond to queries 
from Regulatory authorities, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse Events.  
Subjects are allowed to re-screen for this study one time (except where screen HIV-1 plasma RNA ≥50 
copies/mL or where exclusionary HIV-1 resistance was present).  Re-screening will require a new subject 
number.  A single repeat test (re-test) per analyte or assessment is allowed during the screening period 
to determine eligibility. However, a repeat HIV-1 RNA, if HIV-1 RNA was ≥50 copies/mL is not allowed.   


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Laboratory results obtained from a local lab utilizing the participant’s insurance plan will be used to 
assess eligibility. Source documentation to verify entry criteria must be reviewed by the Principal 
Investigator or designee prior to randomization.  Source documents from other medical facilities must 
be located/retrieved during the screening period.  Under no circumstances may a subject be randomized 
in the absence of source documentation including prior qualifying viral load data (as outlined in the 
Inclusion Criteria). 
 
d. Withdrawal and Stopping Criteria 
Subjects permanently discontinuing study treatments are considered withdrawn from the study.  
Withdrawn subjects will not be replaced.  A subject may withdraw consent and discontinue participation 
in this study at any time at his/her own request.  
 
The investigator may also, at his or her discretion, discontinue the subject from participating in the study 
at any time (e.g. safety, behavioral or administrative reasons).  If a subject withdraws from the study, 
he/she may not be able to request destruction of any samples taken, as these are sent for testing and 
processing at a local laboratory (i.e. Quest, LabCorps, Advent Health), this will be clearly outlined in the 
informed consent.  Subjects are not obligated to state the reason for withdrawal.  However, a reason for 
withdrawal must be documented by the Investigator on the source notes for the 
Completion/Withdrawal visit.  Every effort should be made by the Investigator to follow-up subjects 
who withdraw from the study. 
 
Subjects may have a temporary interruption to their study treatment for management of toxicities.  
Such interruption of study treatment does not require withdrawal from the study; however, this 
decision should be made in conjunction with the Principal Investigator.     
 
Subjects may be prematurely discontinued from the study for any of the following reasons:  
 
• 
Subject or Investigator non-compliance 
• 
At the request of the subject or Investigator 
• 
The subject requires concurrent prohibited medications during the course of the study. The 
subject may remain in the study if in the opinion of the Investigator, such medication will not 
interfere with the conduct or interpretation of the study or compromise the safety of the 
subject.  
 
Subjects must be discontinued from the study for any of the following reasons:  
 
• 
Virologic rebound criteria as specified in Figure 2 are met 
• 
Subject is identified as having been mistakenly screened/randomized with exclusionary 
resistance (see Section 5b) 
• 
Subject requires substitution or dose modification of DTG/3TC or B/F/TAF 
• 
Presence of significant liver toxicity that is possibly drug-related  
• 
Presence of significant renal toxicity that is possibly drug-related  
• 
Grade 4 clinical or laboratory AE that is possibly drug-related  
• 
Allergic reaction or rash that is possibly drug-related at the discretion of the investigator 
• 
Pregnancy (intrauterine), regardless of termination status of pregnancy (Section 5b).  As a 


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reminder, females of reproductive potential who change their minds and desire to be pregnant, 
or who state they no longer are willing to comply with the approved pregnancy avoidance 
methods should also be withdrawn from the study 
• 
Subject loses insurance and has no ability to obtain study treatment or cover required study labs 
through Week 48 
 
If a subject is prematurely or permanently withdrawn from the study, the procedures described in the 
Study Procedures Table (Appendix 1) for the in-clinic Withdrawal visit are to be performed.  All data 
from the Withdrawal visit will be recorded, as they comprise an essential evaluation that should be done 
prior to discharging any subject from the study.   Once the withdrawal visit is completed, the subject will 
be referred back to their regular HIV clinic provider for further evaluation and management. 
 
The following actions must be taken in relation to a subject who fails to attend the clinic for a required 
study visit:  
 
• 
The site must attempt to contact the subject and re-schedule the missed visit as soon as 
possible. 
• 
The site must counsel the subject on the importance of maintaining the assigned visit schedule 
and ascertain whether or not the subject wishes to and/or should continue in the study. 
• 
In cases where the subject is deemed ‘lost to follow-up’, the investigator or designee must make 
every effort to regain contact with the subject (where possible, three telephone calls and if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the subject’s medical record. 
• 
Should the subject continue to be unreachable, only then will he/she be considered to have 
withdrawn from the study with a primary reason of “Lost to Follow-up”. 
 
Management of Virologic Rebound  
 
Participants who meet the criteria listed below will be considered to have virologic rebound: 
 
• 
At any post Day 1 visit, a confirmed rebound in HIV-1 RNA ≥50 copies/mL  
 
Following the initial virologic rebound, participants will be asked to return to the clinic for a scheduled or 
unscheduled blood draw (within 2 to 3 weeks after the date of the original test that resulted in HIV-1 
RNA≥ 50 copies/mL). Participants with HIV-1 RNA values between 50-200 copies/mL should follow the 
algorithm in Figure 2. If virologic rebound is confirmed at the scheduled or unscheduled visit, whole 
blood for HIV-1 DNA archive testing (collected at screening) will also be sent to the lab for processing.  If 
virologic rebound is confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥ 200 
copies/mL, the plasma sample from the confirmation visit will also be sent for HIV-1 genotypic testing.  
After a participant’s first post-Day 1 resistance test, additional testing will be conducted on a case-by-
case basis. Any participant may be discontinued at the investigator’s discretion or per local treatment 
guidelines. If no resistance to study treatment is detected from the genotypes, the participant may  
remain on study treatment and HIV-1 RNA should be analyzed at a new visit (within 2 to 3 weeks after 
date of the second test with HIV-1 RNA ≥50 copies/mL).  Investigators should carefully evaluate the  
benefits and risks of remaining on study treatment for each individual participant and document this 
assessment in the medical record. 
 


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Participants who are noncompliant on an ongoing basis will be considered for discontinuation per the 
investigator’s discretion or local treatment guidelines. Participants who are off study treatment may be 
prematurely discontinued from the study at the discretion of the investigator. Please refer to Figure 2 
for the management of participants who meet the criteria for virologic rebound. 
 
 
Figure 2. Management of Virologic Rebound  
 
 
 
 
 
Participants with HIV-1 RNA ≥50 copies/mL at Study Drug Discontinuation, Week 12, Week 24, or 
Week 48 
 
 
Participants with HIV-1 RNA ≥50 copies/mL at study drug discontinuation, last visit, or last Week 12, 24 
or 48 result will be considered virologic rebounders. Participants with HIV-1 RNA ≥50 copies/mL at Week 
12, 24 or Week 48 will be asked to return for an unscheduled visit within the visit window for a  
retest and have whole blood for HIV-1 DNA archive testing (collected at screening) sent to the lab for 
processing.   Participants with HIV-1 RNA ≥200 copies/mL at study drug discontinuation, last visit, or 
Week 12, 24 or 48 visit, will also have HIV-1 genotype resistance testing conducted. 


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Management of patients with significant hepatic toxicity 
 
Liver chemistry stopping and increased monitoring criteria have been designed to assure subject safety 
and evaluate liver event etiology during administration of study drug and the follow-up period (in 
alignment with the FDA premarketing clinical liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174
090.pdf 
 
For any participant meeting one of the criteria outlined in Table 1 or Table 2, or if the Investigator 
believes that it is in the best interest of the participants, the investigator will follow the required actions 
and follow up assessments also outlined in these tables. 
 
Table 1 
Liver Chemistry Stopping Criteria - Liver Stopping Event 
ALT absolute 
ALT ≥ 8xULN 
ALT increase 
ALT ≥ 5xULN but <8xULN persists for ≥2 weeks (with bilirubin <2xULN and no 
signs or symptoms of acute hepatitis or hypersensitivity) 
Bilirubin1, 2 
ALT ≥3xULN and bilirubin ≥ 2xULN (>35% direct bilirubin)  
INR2  
ALT ≥ 3xULN and International normalised ratio (INR)>1.5, if INR measured 
Cannot 
Monitor 
ALT ≥ 5xULN but <8xULN and cannot be monitored weekly for >2 weeks 
(See Table 2 for actions where subjects CAN be monitored weekly for >2 
weeks) 
Symptomatic3 ALT ≥ 3xULN (if baseline ALT is <ULN) with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity 
ALT ≥ 3x baseline (if baseline ALT>ULN) with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity 
Required Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
• Immediately hold DTG/3TC or B/F/TAF  
• If a causal relationship between the liver 
event and DTG/3TC or B/F/TAF cannot be 
ruled out, then DTG/3TC or B/F/TAF must 
be permanently discontinued and the 
• Viral hepatitis serology, including: 
Hepatitis A immunoglobulin M (IgM) 
antibody; 
HBsAg and hepatitis B core antibody; 
Hepatitis C RNA; 


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Subject not rechallenged due to the risk 
of a recurrent reaction.   
• Report the event to the ViiV/GSK safety 
team by telephone within 24 hours. 
• Events of possible drug-induced liver injury 
with hyperbilirubinemia2 will be reported 
to ViiV/GSK as serious adverse events 
(SAEs) using the SAE CRF. 
• Complete the liver event case report form 
for all events meeting liver stopping 
criteria, and submit to ViiV/GSK within one 
week of first becoming aware of the event 
• Perform liver event follow up assessments.  
• Monitor the subject until liver chemistries 
resolve, stabilise, or return to within 
baseline (see MONITORING below). 
• All participants who experience a liver 
stopping event in this clinical trial will be 
permanently withdrawn from the study. 
 
MONITORING: 
• Make every reasonable attempt to have 
subjects return to clinic within 24 hours for 
repeat liver chemistries (include ALT, 
aspartate aminotransferase, alkaline 
phosphatase, bilirubin) and perform liver 
event follow up assessments at the local 
laboratory as described to the right.  
• A specialist or hepatology consultation can 
be considered. 
• Monitor subjects twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline. 
Hepatitis E IgM antibody. 
• Cytomegalovirus IgM antibody. 
• Epstein-Barr viral capsid antigen IgM 
antibody (or if unavailable, obtain 
heterophile antibody or monospot 
testing). 
• Syphilis screening. 
• Drugs of abuse screen, including alcohol. 
Record alcohol use on the liver event 
case report form 
• Serum acetaminophen adduct High 
Performance Liquid Chromatography 
assay (quantifies potential 
acetaminophen contribution to liver 
injury in subjects with definite or likely 
acetaminophen use in the preceding 
week [19]).   
• Serum creatinine kinase and lactate 
dehydrogenase. 
• Fractionate bilirubin, if total bilirubin 
≥1.5xULN. 
• Obtain complete blood count with 
differential to assess eosinophilia. 
• Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G (or 
gamma globulins). 
• Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease. Complete Liver 
Imaging and/or Liver Biopsy case report 
form if applicable 
• Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 


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remedies, other over the counter 
medications. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is 
not immediately available, discontinue study treatment for that subject if ALT ≥ 3xULN and bilirubin ≥ 
2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT ≥ 3xULN and bilirubin ≥ 2xULN (>35% direct bilirubin) or ALT ≥ 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury must be reported as a serious adverse event; INR 
measurement is not required and the threshold value stated will not apply to subjects receiving 
anticoagulants 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, 
rash or eosinophilia).  Record the appearance or worsening of any such clinical symptoms on the adverse 
event report form. 
Table 2 
Liver Chemistry Increased Monitoring Criteria 
Criteria 
Actions 
ALT ≥5xULN and <8xULN and 
bilirubin <2xULN without 
symptoms believed to be related 
to liver injury or hypersensitivity, 
and who can be monitored weekly 
for >2 weeks. 
• Notify the ViiV/GSK safety team within 24 
hours of learning of the abnormality to 
discuss subject safety.  
• Subject can continue study treatment   
• Subject must return weekly for repeat liver 
chemistries (ALT, aspartate 
aminotransferase, alkaline phosphatase, 
bilirubin) until resolution, stabilisation (ALT 
<5×ULN on 2 consecutive evaluations) or 
return to within baseline   
• If at any time subject meets the liver 
chemistry stopping criteria, proceed as 
described above 
 
 
 
 
Liver Safety- Study Treatment Restart 
 
Participants who meet liver stopping criteria for any reason will be discontinued from study treatment 
and permanently withdrawn from this clinical trial. 
 
Management of patients with significant renal toxicity  
 


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Treatment with DTG/3TC must be discontinued in any subject developing moderate to severe renal 
impairment during the study, as indicated by confirmed creatinine clearance measuring <50 mL/min via 
the Cockcroft-Gault method (initial abnormal value must be confirmed by a repeat creatinine clearance 
assessment within 2 weeks.)  These participants will be permanently withdrawn from the study. 
 
 
e. Subject and Study Completion 
 
Subjects are considered to have completed the study if they satisfy one of the following:  
 
• 
randomly assigned to either treatment group and completed the Week 48 visit 
• 
the subject no longer derives clinical benefit 
• 
the subject meets a protocol-defined reason for discontinuation 
 
Subjects completing the study will be referred to their regular HIV clinic provider for further evaluation 
and management. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6. Study Treatment 
a. Investigational Product and Other Study Treatment 
 
The term ‘study treatment’ is used throughout the protocol to describe any combination of products 
received by the subject as per the protocol design. Study treatment may therefore refer to the individual 
study treatments or the combination of those study treatments.  All study treatments will be 
administered at the approved dosages.  Participants will be responsible for utilizing their insurance plan 
to obtain the study treatment, DTG/3TC FDC (Dovato™) from a local pharmacy.  Subjects randomly 
assigned to continue B/F/TAF up to 48 weeks will also be responsible for utilizing their insurance plan to 
obtain B/F/TAF (Biktarvy™) from a local pharmacy.  The study team will work with all study subjects to 
minimize out of pocket co pays for drug coverage through the use of manufacturer or other external 
assistance programs. DTG/3TC must be stored in a secure area under the appropriate physical 
conditions for the product.  For further details on storage, access and administration of study 
treatments, refer to product labels for Dovato™ [14] and Biktarvy™ [18]. 
 
 
b. Protocol-Permitted Substitutions 
There are no protocol-permitted substitutions for DTG/3TC or B/F/TAF allowed for this study. 
 
c. Treatment Assignment  
Participants will be assigned a screening number at the time of consent. Randomization/Day 1 visits 
cannot occur until participant eligibility has been confirmed.  
 
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or designee 
will randomize the participant using a randomization code developed by the study statistician. Once a 
participant number has been assigned to a participant, it will not be reassigned to any other participant. 
The participant number assignment and randomization may be performed up to 3 days prior to the in-
clinic Day 1 visit provided that all screening procedures have been completed and participant eligibility 
has been confirmed.  
 
Participants will be randomized in a 2:1 ratio to Treatment Group 1 or Treatment Group 2.  
 
Treatment Group 1 (n=148):FDC of DTG/3TC (50 mg/300 mg) administered orally, once daily (QD), 
without regard to food.  
 
Treatment Group 2 (n=74):Stay on FDC of B/F/TAF (50 mg/200 mg/25 mg) administered orally, QD, 
without regard to food. 
 
No assignment of study drug bottles will occur in this protocol as participants will expected to utilize 
their insurance plan to obtain commercially available DTG/3TC or B/F/TAF from a local pharmacy.   
 
Randomization will be stratified by race and gender to ensure equal numbers of African Americans and  
females in each study arm. 
 


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d. Planned Dose adjustments 
 
No dose adjustments are permitted in this study for DTG/3TC or for B/F/TAF. 
 
e. Blinding 
 
This will be an open-label study and therefore no blinding is required. 
 
f. Packaging and Labeling 
Participants will be responsible for utilizing their insurance plan to obtain commercially available 
DTG/3TC or B/F/TAF from a local pharmacy.  The site and study team will not be responsible for the 
packaging and labeling of the study treatments. 
 
g. Preparation/Handling/Storage/Accountability 
No special preparation of study treatment is required.  
 
Participants will be instructed that all study treatments must be stored in a secure environmentally 
controlled area in accordance with the labelled storage conditions.   
 
Under normal conditions of handling and administration, study treatment is not expected to pose 
significant safety risks to participants or site staff. 
 
Methods to evaluate study treatment accountability will not be used in this protocol as participants will 
be responsible for utilizing their insurance plan to obtain commercially available DTG/3TC or B/F/TAF 
from a local pharmacy and will be instructed to store the study treatment at home according to 
instructions on the label. 
 
h. Compliance with study treatment administration 
When subjects self-administer study treatment(s) at home, compliance with study drugs will be assessed 
through querying the subject during the site visits (i.e. through use of the Visual Analog Scale (VAS) 
Adherence survey) and documented in the source documents.  Treatment start and stop dates also will 
be recorded in the source documents. 
 
i. Treatment after the end of the study 
The investigator is responsible for ensuring that consideration has been given to the post-study care of 
the subject’s medical condition.  At the end of the study at Week 48, subjects will be referred to their 
regular HIV clinic provider for further evaluation and management.  The clinic provider will be 
responsible for decisions regarding appropriate HIV therapy once subjects have completed the study. 
 
j. Prior and concomitant medications 
Concomitant medications (prescription and non-prescription) should be prescribed by the relevant 


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health care provider/investigator and administered only as medically necessary during the Randomized 
phases of the study (except prohibited medications as described below).  Chemoprophylaxis for HIV-
associated conditions is encouraged, if appropriate, at the discretion of the subject and their physician. 
All concomitant medications, blood products, and vaccines taken during the study will be recorded in 
the source documentation with dates of administration.  
 
Because non-HIV vaccines may cause a temporary increase in the level of HIV-1 plasma RNA, it is highly 
recommended that a vaccine, if necessary, be given during or immediately after a scheduled visit after 
all laboratory tests have been drawn and only when scheduled visits are ≥4 weeks apart.  This approach 
will minimize the risk of nonspecific increases in the level of HIV-1 plasma RNA at the next scheduled 
assessment. 
 
DTG/3TC should be administered 2 hours before or 6 hours after taking antacid or laxative products 
containing polyvalent cations (e.g. aluminum and magnesium), sucralfate, or calcium supplements.  
Proton pump inhibitors and H2-antagonists may be used in place of antacids with no scheduling 
restrictions.  Concurrent administration with multivitamins is acceptable.  Iron supplements can be 
taken with study treatment provided that all are taken together with a meal. Under fasted conditions, 
DTG/3TC should be given 2 hours prior to OR 6 hours after iron supplements.  
 
Metformin concentrations may be increased by DTG.  A dose adjustment of metformin should be 
considered when starting and stopping co-administration of dolutegravir with metformin, to maintain 
glycemic control.  
 
Clinical monitoring is recommended for subjects taking methadone, as methadone maintenance therapy 
may need to be adjusted in some subjects.  
 
Non-protocol defined treatments or medical interventions (e.g., physical therapy, radiotherapy, surgical 
procedures) are permitted during the study for appropriate medical management of the subject. 
 
Prohibited Medications and Non-Drug Therapies 
 
The following concomitant medications or therapies are not permitted at any time during the study: 
 
• 
HIV immunotherapeutic vaccines  
• 
Other experimental agents, ART drugs not otherwise specified in the protocol, cytotoxic 
chemotherapy, or radiation therapy 
• 
Systemically administered immunomodulators (such as interleukin and interferon agents) are 
prohibited through Week 48.  This includes topical agents with substantial systemic exposure 
and systemic effects.  Use of topical imiquimod is permitted 
• 
HCV therapy up to Week 48 
 
For more information on prohibited medications and drug-drug interactions in relation to other 
antiretrovirals used in comparator regimens, please refer to the package insert for B/F/TAF [18]. 
 
Prohibited Medications for Subjects Receiving DTG/3TC 
 
Medications (or their equivalents) that may cause decreased concentrations of DTG and/or 3TC and 
must not be administered concurrently with DTG/3TC:  


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33 
 
 
• 
Carbamazepine 
• 
Oxcarbamazepine 
• 
Phenobarbital 
• 
Phenytoin 
• 
Rifampin 
• 
Rifapentine 
• 
St. John’s wort 
• 
Dofetilide (DTG may inhibit renal tubular secretion resulting in increased dofetilide 
concentrations and potential for toxicity). 
• 
Fampridine/Dalfampridine 
 
Note: Any prohibited medications that decrease dolutegravir concentrations should be discontinued for 
a minimum of four weeks or a minimum of three half-lives (whichever is longer) prior to the first dose.  
Any other prohibited medications should be discontinued for a minimum of two weeks or a minimum of 
three half-lives (whichever is longer) prior to the first dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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7. Study Procedures 
The study procedures to be conducted for each participant enrolled in the study are presented in 
tabular form in Appendix 1 and are described in the text that follows.  
 
The investigator must document any deviation from protocol procedures and notify any applicable 
regulatory agencies. 
 
a. Participant enrollment and treatment assignment  
 
It is the responsibility of the Investigator to ensure that participants are eligible for study prior to 
enrollment. Please refer to Section 7b below for details about randomization and treatment assignment. 
b. Pretreatment Assessments 
 
Screening Visit 
 
Participants will be screened within 42 days before Day 1 to determine eligibility for participation in the 
study.  
 
The following will be performed and documented at screening: 
 
• 
Obtain written informed consent(s) 
• 
Obtain demographic information, including gender at birth, and race 
• 
Obtain screening number using randomization code  
• 
Obtain medical history including history of HIV-1 disease-related events, and prior medications 
within 30 days of the screening visit 
• 
If available, obtain documentation of historical genotype(s) (not required for entry to study) 
• 
Complete physical examination (urogenital/anorectal exams will be performed at the discretion 
of the Investigator)  
• 
Height 
• 
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight and waist circumference measurement 
• 
Obtain blood and urine samples as described in Section 7e 
• 
Review concomitant medications 
• 
Record any SAEs and all AEs related to protocol mandated procedures occurring after signing of 
the consent form. 
 
Participants meeting all of the inclusion criteria, and none of the exclusion criteria, will return to the 
clinic within 42 days after screening for the Day 1 Visit. Participants randomized to Treatment Group 1 
must continue to take their prior treatment regimen up until the day before their scheduled Day 1 visit. 
Participants randomized to Treatment Group 2 will continue to take their prior treatment regimen until  
the end of the study at Week 48. From the time of obtaining informed consent through the first  
administration of study treatment record all SAEs, as well as any AEs related to protocol-mandated 
procedures in the source documentation. All other untoward medical occurrences observed during the 


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35 
 
screening period, including exacerbation or changes in medical history are to be captured in the medical 
history in the source documents 
 
Randomization 
 
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or designee 
will randomize the participant using the randomization code provided by the study statistician.  Once a 
participant number has been assigned to a participant, it will not be reassigned to any other participant. 
The participant number assignment and randomization may be performed up to 3 days prior to the in-
clinic Day 1 visit, provided that all screening procedures have been completed and participant eligibility 
has been confirmed.  This study aims to enroll 30% of participants who identify as female and African 
American.  Randomization will be stratified by gender and race to ensure equal numbers of females and 
African American participants in each study arm. 
 
c. Day 1 Assessments 
 
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have confirmed 
eligibility before proceeding with the Day 1 visit.  
 
Participants must complete all study procedures before being administered FDC of DTG/3TC:  
• 
HIV Symptoms Distress Module Index and HIV Treatment Satisfaction Status (HIV-TSQs) 
(completed by participants in Treatment group 1&2) 
• 
Visual Analogue Scale (VAS) Adherence Questionnaire is to be completed by participants in 
Treatment Group 2 only.  Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires. 
• 
Willingness to Switch survey (to be completed by participants in Treatment group 1 only) 
• 
Review of AEs and changes in concomitant medications 
• 
Symptom-directed physical examination 
• 
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight and waist circumference 
• 
Obtain urine sample for pregnancy testing in female participants of reproductive potential 
• 
Confirmation that participants in Treatment Group 1 were able to obtain DTG/3TC from their 
local pharmacy using their insurance plan  
• 
Observed first dose administration of FDC of DTG/3TC in Treatment Group 1.  If the participant 
has taken their prior regimen on Day 1, prior to the Study Visit, they should be instructed to take 
their first dose of DTG/3TC the following day and dosing can be confirmed by phone. 
• 
Participants should be instructed to take FDC of DTG/3TC without regard to food. The 
participant should be counseled regarding the importance of adherence and taking their study 
medication at approximately the same time each day as directed by the Investigator. 
 
d. Treatment Assessments (W1-48) 
 
All study visits are to be completed within ± 7 days of the protocol specified visit date (based on the Day 
1 visit), unless otherwise specified.   
 


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36 
 
The following evaluations are to be completed at the Weeks 1 and 36* phone call, unless otherwise 
specified. 
 
• 
Review of AEs and changes in concomitant medications 
• 
Informal adherence assessment by asking “How many doses of study treatment have been 
missed in the last 7 days and in inquiring about reasons for missed doses” 
• 
Adherence counseling by investigator or designee 
 
*Week 36 assessment will also include clinical laboratory assessments as specified below 
 
The following evaluations are to be completed at Weeks 4, 12, 24, and 48 unless otherwise specified.  
 
• 
HIV Symptoms Distress Module Index is to be completed by the participant at Weeks 4, 12, 24 
and 48. HIV Treatment Satisfaction Change (HIV-TSQc) is to be completed at Weeks 4 and 24 
only. VAS Adherence Questionnaire is to be completed by the participant at Weeks 4, 12, 24 and 
48.  The Columbia-Suicide Severity Rating Scale (C-SSRS) is to be completed by the participant at 
Weeks 4, 12, 24 and 48. Participant is to read questionnaire by himself/herself and write/mark 
answers directly onto questionnaires 
• 
Review of AEs and changes in concomitant medications 
• 
Complete physical examination (Weeks 24 and 48) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination, as 
needed 
• 
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight and waist circumference 
• 
Obtain blood and urine samples as described in Section 7e 
• 
Document any changes in insurance and confirm participant ability to still obtain DTG/3TC or 
B/F/TAF from their local pharmacy 
• 
Participants who meet the criteria for virologic rebound will be managed according to the 
Management of Virologic Rebound Schema found in Figure 2 
 
After completion of the Week 48 assessment, participants will exit the study and be referred to their 
regular HIV clinic provider for further evaluation and management. 
 
e. Clinical Laboratory Assessments 
Blood and urine samples will be collected throughout the study as outlined below, and in the Study 
Procedures Table found in Appendix 1. 
 
Blood Samples 
 
Blood sample collection for the following laboratory analyses will be performed at the visits specified 
below:  
 
Serum pregnancy test (all female participants). If the test is positive at the screening visit, the participant 
will not be enrolled (Screening) 
• 
FSH test:  Only required for female participants who are <54 years old and have stopped 
menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure  


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37 
 
(Screening only) 
 
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, total protein, albumin, bicarbonate, 
blood urea nitrogen (BUN), chloride, creatinine, eGFR, glucose, potassium, sodium and calcium 
(Screening, Weeks 4, 12, 24, 36 and 48) 
 
Metabolic assessments: Fasting (no food or drinks, except water, at least 8hours prior to blood 
collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, and triglycerides) (Screening, 
Weeks 24, and 48) 
• 
If the participant has not fasted prior to the visit, the visit may proceed, but the participant must 
return within 72 hours in a fasted state to draw blood for the metabolic assessments 
 
Hematology profile: complete blood count (CBC) with differential and platelet count (Screening, Weeks 
4, 12, 24, 36 and 48) 
 
CD4+ cell count and percentage (Screening, Weeks 24, 36, 48) 
 
Plasma HIV-1 RNA. Any subsequent HIV-1 genotype testing will be performed as described in Section 5d 
(Screening, Weeks 4, 12, 24, 36 and 48) 
 
Whole blood for HIV-1 DNA archive testing as described in Section 5d (sample collected at Screening 
and stored for potential future testing)  
 
HBV blood panel: Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) 
and Hepatitis B virus core antibody (HbcAb) (Screening, Weeks 24, 48).  If screening results reveal the 
patient is HBV immune (HBsAb positivity), the HBV blood panel will not be collected for the remainder of 
the study period. 
• 
The following tests will be conducted if the following criteria are met: 
o If positive HBsAg: reflex testing for plasma HBV DNA, Hepatitis B virus e-antigen 
(HBeAg) and Hepatitis B virus e-Antibody (HBeAb).  Patients who test positive 
for HBsAg and are randomized to the DTG/3TC arm will be prematurely 
discontinued from the study. 
o If positive HBcAb with negative HBsAg and negative HBsAb: reflex testing for 
plasma HBV DNA, HBeAg and HBeAb.  Patients who test positive for any of these 
markers and are randomized to the DTG/3TC arm will be prematurely 
discontinued from the study. 
 
HCV antibody (Ab) serology (Screening, Weeks 24, and 48). Participants who are HCV Ab positive will 
have an HCV RNA test performed.  
 
Urine Samples  
 
Urine sample collection for the following laboratory analyses will be performed at the visits specified 
below: 
 
Urinalysis (Screening, Weeks 4, 12, 24, 36 and 48) 
 
Urine pregnancy testing for persons of childbearing potential (Day 1, Weeks 4, 12, 24, 36 and 48).  If the 


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38 
 
urine pregnancy test is positive, a serum pregnancy test will also be performed. 
 
f. Assessments for Premature Discontinuation from Study 
 
If the participant discontinues their study regimen prior to the Week 48 visit, the participant will be 
asked to return to the clinic within 72 hours of stopping study treatment for the Early Study Drug 
Discontinuation Visit which will also serve as the End of Study visit.   
 
The following evaluations are to be completed at the Early Study Drug Discontinuation Visit: 
 
o Review of AEs and changes in concomitant medications 
o Complete physical examination (urogenital/anorectal exams will be performed at the discretion 
of the Investigator) 
o Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight and waist circumference 
o Obtain blood and urine samples as described for the Week 48 visit above 
 
At the Early Study Drug Discontinuation Visit, any evaluations showing abnormal results indicating that 
there is a possible or probable causal relationship with the study treatment regimen, will be evaluated 
and managed by the participant’s regular HIV clinic provider.  The study team will request these clinical 
records to follow and document the resolution of any abnormal results that developed during the study. 
 
g. End of Study 
The end of study will be the last patient’s last observation (or visit).  After the end of study visit, any 
ongoing AEs or evaluations showing abnormal results indicating that there is a possible or probable 
causal relationship with the study treatment regimen, will be evaluated and managed by the 
participant’s regular HIV clinic provider.  The study team will request these clinical records to follow and 
document the resolution of any abnormal results that developed during the study. 
 
 
h. Post Study Care 
After a participant has completed/terminated their participation in the study, long-term care for the 
participant will remain the responsibility of their primary treating physician. 
 
 
i. Management of virologic rebound 
 
Participants with virologic rebound will be managed according to the Management of Virologic Rebound 
schema in Figure 2. 
 
 
 
 
 
 


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8. Safety 
 
a. Adverse Events (AEs) and Serious Adverse Events (SAEs) 
Definitions of Adverse Events and Serious Adverse Events 
 
Adverse Events 
 
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a 
medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with 
the use of a medicinal product, whether or not considered related to the medicinal product. AEs may 
also include pre-or post-treatment complications that occur as a result of protocol specified procedures, 
lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting events that 
increase in severity or change in nature during or as a consequence of participation in the clinical study 
will also be considered AEs.  
 
An AE does not include the following: 
 
• 
Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion. 
The condition that led to the procedure may be an adverse event and must be reported 
• 
Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen 
• 
Situations where an untoward medical occurrence has not occurred (e.g. hospitalization for 
elective surgery, social and/or convenience admissions) 
• 
Overdose of study treatment without clinical sequelae 
• 
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is not an AE. It is 
considered to be pre-existing and should be documented on the medical history case report 
form (CRF). 
 
Serious Adverse Events 
 
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:  
 
• 
Death 
• 
Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the participant 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.) 
• 
In-patient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant disability/incapacity 
• 
A congenital anomaly/birth defect 
• 
All events of possible drug-induced liver injury with hyperbilirubinemia defined as ALT greater 
than or equal to 3xULN and bilirubin greater than or equal to 2xULN (>35% direct) 
• 
A medically important event or reaction: such events may not be immediately life-threatening 
or result in death or hospitalization but may jeopardize the participant or may require 
intervention to prevent one of the other outcomes constituting SAEs. Examples of medically 


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important events include intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; and 
development of drug dependency or drug abuse.  
 
Assessments of Adverse Events and Serious Adverse Events 
 
The investigator or qualified sub investigator is responsible for assessing AEs and SAEs for causality and 
severity, and for final review and confirmation of accuracy of event information and assessments. 
 
Assessment of Causality for Study Drugs and Procedures 
 
The investigator or qualified sub investigator is responsible for assessing the relationship to study 
treatment using clinical judgment and the following considerations:  
 
• 
No: Evidence exists that the adverse event has an etiology other than the study treatment. For 
SAEs, an alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication). 
 
• 
Yes: There is reasonable possibility that the event may have been caused by the study 
treatment. It should be emphasized that ineffective treatment should not be considered as 
causally related in the context of adverse event reporting.  
 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) should be 
assessed using the following considerations:  
 
• 
No: Evidence exists that the adverse event has an etiology other than the study procedure. 
 
• 
Yes: The adverse event occurred as a result of protocol procedures, (eg, venipuncture) 
 
 
Assessment of Severity 
 
AE severity should be recorded and graded according to the Division of AIDS (DAIDS) Table for Grading 
the Severity of Adult and Pediatric Adverse Events [20]. For adverse events associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of the 
underlying conditions; this may or may not be in agreement with the grading of the laboratory 
abnormality. The distinction between the seriousness and the severity of an adverse event should be 
noted. Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it met one 
of the criteria for serious events. For AEs associated with laboratory abnormalities, the event should be 
graded on the basis of the clinical severity in the context of the underlying conditions; this may or may 
not be in agreement with the grading of the laboratory abnormality. 
 
 
 
b. Time period and frequency of collecting AE and SAE info 


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41 
 
• 
Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures, 
invasive tests, or change in existing therapy) or related to study treatment will be recorded from 
the time a subject consents to participate in the study up to and including any follow-up contact. 
• 
AEs will be collected from the start of Study Treatment until the follow-up contact at the 
timepoints specified in the Study Procedures Table in Appendix 1.  
• 
Medical occurrences that begin prior to the start of study treatment but after obtaining 
informed consent may be recorded on the Medical History/Current Medical Conditions section 
on the source documents. 
• 
All SAEs considered possibly related to study treatment will be recorded and reported to 
ViiV/GSK within 24 hours of first becoming aware of the event. The ViiV Healthcare (VH) CRF 
with toxicity Grade (SAE) and VH CRF with intensity (SAE) forms will be used to record and 
report these events. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study subjects. However, if 
the investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must notify ViiV/GSK within 24 hours of first 
becoming aware of the event utilizing the methods described above. 
 
c. Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and non-leading 
verbal questioning of the subject is the preferred method to inquire about AE occurrence.  Appropriate 
questions include:  
• 
“How are you feeling?” 
• 
“Have you had any (other) medical problems since your last visit/contact?” 
• 
“Have you taken any new medicines, other than those provided in this study, since your last 
visit/contact?” 
 
d. Follow up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts.  All SAEs, and non-serious AEs of special interest will be followed until 
resolution, until the condition stabilizes, until the event is otherwise explained, or until the subject is lost 
to follow-up. 
 
e. Reporting requirements for AEs and SAEs 
SAEs will be reported to ViiV/GSK per applicable guidelines for Investigator Sponsored studies utilizing 
ViiV/GSK products as specified above in Section 8b. 
SAEs will be reported to applicable regulatory authorities per IRB SAE reporting guidelines. 
 
f. Pregnancy 


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Information on the occurrence of pregnancies in female subjects will be collected over the period 
starting at Screening and ending at the final Follow-up visit. Pregnancies that occur following the first 
dose of study drug will be reported to the Antiretroviral Pregnancy Registry and ViiV/GSK within 24 
hours of first becoming aware of the event.  The pregnancy must be followed up to determine outcome 
(including premature termination) and status of mother and child(ren).  The VH pregnancy initial report 
and pregnancy follow-up report CRF will be used to record and report these events.  Pregnancy 
complications and elective terminations for medical reasons must be reported as an AE or SAE.  
Spontaneous abortions must be reported as SAEs. Any SAE occurring in association with a pregnancy 
brought to the investigator’s attention after the subject has completed the study and considered by the 
investigator as possibly related to the study treatment must be reported to ViiV/GSK within 24 hours of 
first becoming aware of the event.   
 
Any female who becomes pregnant (intrauterine) while participating in this study must be withdrawn 
from the study and must discontinue study drug immediately. 
 
 
g. Physical Exams 
Physical exams should be conducted as part of normal routine clinical care per the Study Procedures 
Table (Appendix 1) and findings will be recorded in the source documents.  Abnormalities noted during 
any exam may be captured in the current medical conditions or AE logs. 
 
h. Vital Signs 
Vital sign collection including, weight and waist circumference should be conducted as part of normal 
routine clinical care per the Study Procedures Table (Appendix 1) and findings will be recorded in the 
source documents.  Abnormalities in vital signs during any visit may be captured in the current medical 
conditions or AE logs. 
 
i. Clinical Safety Laboratory Assessments 
All protocol required laboratory assessments, as defined in Section 7e must be performed by the local 
lab preferred by the patient’s insurance plan.  All blood and urine samples will be collected at the study 
visit and will be transported to the local lab for processing.  Laboratory assessments must be  
 
conducted in accordance with the Study Procedures Table (Appendix 1). Laboratory requisition forms 
must be completed, and samples must be clearly labelled with the subject name, date of birth, and visit 
date. Details for the preparation and shipment of samples will be provided by the local laboratory  
 
and are generally available on the local laboratory website.  Reference ranges for all safety parameters 
will be provided by the local laboratory. If additional non-protocol specified laboratory assessments are 
performed at the local laboratory and result in a change in subject management or are considered 
clinically significant by the investigator (e.g. AE, SAE or dose modification) the results must be recorded 
in the source documents. Labs will be graded by the investigator according to the DAIDS toxicity scales 
[20].   
 
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. However, 
laboratory abnormalities (i.e. clinical chemistry, hematology, and urinalysis) that require medical or 


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surgical intervention or lead to study treatment interruption, modification, or discontinuation must be 
recorded as an AE, as well as an SAE, if applicable. 
 
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the clinical 
severity in the context of the underlying conditions; this may or may not be in agreement with the 
grading of the laboratory abnormality. 
 
 
j. Toxicity Management 
 
In the event of a discontinuation of study treatment for suspected drug induced liver injury, other 
clinically significant liver chemistry elevations, severe skin reaction or hypersensitivity reaction, subjects 
should not be rechallenged with study treatment due to the risk of a recurrent reaction. These subjects 
should be permanently discontinued from the study and referred to their routine HIV provider for 
alternative ARV selection and management. 
 
Hypersensitivity and rash  
 
Allergic Reaction 
 
Subjects may continue study treatment for Grade 1 or 2 allergic reactions at the discretion of the 
Investigator. The subject should be advised to contact the Investigator immediately if there is any 
worsening of symptoms or if further systemic signs or symptoms develop. Antihistamines, topical 
corticosteroids, or antipruritic agents may be prescribed.  
 
Subjects with Grade ≥3 allergic reactions that are considered to be possibly or probably related to study 
treatment should permanently discontinue the study treatment and be withdrawn from the study. 
Subjects should be treated as clinically appropriate and followed until resolution of the adverse event. 
 
Rash 
 
Mild to moderate rash is an expected adverse reaction for DTG-containing antiretroviral therapy. 
Episodes generally occur within the first ten weeks of treatment, rarely require interruptions or 
discontinuations of therapy and tend to resolve within two to three weeks. The index case of a 
hypersensitivity reaction with DTG involved a profuse, purpuric and coalescing leukocytoclastic vasculitis 
as well as clinically significant liver chemistry elevations. Other than this case, no other instances of 
serious skin reaction, including Stevens-Johnson Syndrome, toxic epidermal necrolysis and erythema 
multiforme have been reported for DTG in clinical trials. 
 
Subjects with an isolated Grade 1 rash may continue study treatment at the Investigator’s discretion. 
The subject should be advised to contact the Investigator immediately if there is any worsening of the 
rash, if any systemic signs or symptoms worsen, or if mucosal involvement develops. 
 
Subjects may continue study treatment for an isolated Grade 2 rash. However, the study treatment (and 
all other concurrent medication(s) suspected in the Investigators causality assessment) should be 
permanently discontinued for any Grade ≥2 rash that is associated with an increase in ALT. The subject 
should be advised to contact the physician immediately if rash fails to resolve (after more than two 
weeks), if there is any worsening of the rash, if any systemic signs or allergic symptoms develop, or if 


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mucosal involvement develops. 
 
Subjects should permanently discontinue study treatment (and all other concurrent medication(s) 
suspected in the Investigators causality assessment) for an isolated Grade 3 or 4 rash, and the subject 
should be withdrawn from the study. Subjects should be treated as clinically appropriate and followed 
until resolution of the adverse event. 
 
The rash and any associated symptoms should be reported as adverse events (see Section 8e) and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS [Division of ADS] 
toxicity gradings). 
 
If the etiology of the rash can be diagnosed as being unrelated to study treatment and due to a specific 
medical event or a concomitant non-study medication, routine management should be performed, and 
documentation of the diagnosis provided. 
 
Liver safety criteria 
 
Liver Chemistry Stopping and Follow up Criteria 
 
Liver chemistry stopping and increased monitoring criteria have been designed to assure subject safety 
and evaluate liver event etiology during administration of study drug and the follow-up period (in 
alignment with the FDA premarketing clinical liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174
090.pdf 
 
For any participant meeting one of the criteria outlined in Table 1 or Table 2, or if the Investigator 
believes that it is in the best interest of the patients, the Investigator must follow the required actions 
and follow up assessments also outlined in these tables. 
 
Table 3 Liver Chemistry Stopping Criteria - Liver Stopping Event 
ALT absolute 
ALT ≥ 8xULN 
ALT increase 
ALT≥ 5xULN but <8xULN persists for ≥2 weeks (with bilirubin <2xULN and no signs or 
symptoms of acute hepatitis or hypersensitivity) 
Bilirubin1, 2 
ALT ≥ 3xULN and bilirubin ≥ 2xULN (>35% direct bilirubin)  
INR2  
ALT ≥ 3xULN and International normalised ratio (INR)>1.5, if INR measured 
Cannot 
Monitor 
ALT ≥ 5xULN but <8xULN and cannot be monitored weekly for >2 weeks 
(See Table 2 for actions where subjects CAN be monitored weekly for >2 weeks) 
Symptomatic3 
ALT ≥3xULN (if baseline ALT is £ULN) with symptoms (new or worsening) believed to 
be related to liver injury or hypersensitivity 
ALT ≥ 3x baseline (if baseline ALT>ULN) with symptoms (new or worsening) believed 
to be related to liver injury or hypersensitivity 
Required Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
• 
Immediately hold DTG/3TC or B/F/TAF.  
• 
If a causal relationship between the liver event 
• 
Viral hepatitis serology, including: 
Hepatitis A immunoglobulin M (IgM) 


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and DTG/3TC or B/F/TAF cannot be ruled out, 
then DTG/3TC or B/F/TAF must be 
permanently discontinued and the Subject not 
rechallenged due to the risk of a recurrent 
reaction.   
• 
Report the event to the GSK/ViiV safety team 
by telephone within 24 hours. 
• 
Events of possible drug-induced liver injury 
with hyperbilirubinemia2 will be reported to 
GSK/ViiV as SAEs using the SAE CRF. 
• 
Complete the liver event CRF for all events 
meeting liver stopping criteria, and submit to 
GSK/ViiV within one week of first becoming 
aware of the event 
• 
Perform liver event follow up assessments.  
• 
Monitor the subject until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING below). 
• 
All participants who experience a liver 
stopping event in this clinical trial will be 
permanently withdrawn from the study. 
 
 
MONITORING: 
• 
Make every reasonable attempt to have 
subjects return to clinic within 24 hours for 
repeat liver chemistries (include ALT, 
aspartate aminotransferase, alkaline 
phosphatase, bilirubin) and perform liver 
event follow up assessments at the local 
laboratory as described to the right.  
 
• 
A specialist or hepatology consultation 
may be considered. 
 
 
• 
Monitor subjects twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline. 
antibody; HBsAg and hepatitis B core 
antibody; Hepatitis C RNA; Hepatitis E 
IgM antibody. 
• 
Cytomegalovirus IgM antibody. 
• 
Epstein-Barr viral capsid antigen IgM 
antibody (or if unavailable, obtain 
heterophile antibody or monospot 
testing). 
• 
Syphilis screening. 
• 
Drugs of abuse screen, including 
alcohol. Record alcohol use on the liver 
event case report form 
• 
Serum acetaminophen adduct High 
Performance Liquid Chromatography 
assay (quantifies potential 
acetaminophen contribution to liver 
injury in subjects with definite or likely 
acetaminophen use in the preceding 
week [19]).   
• 
Serum creatinine kinase and lactate 
dehydrogenase. 
• 
Fractionate bilirubin, if total 
bilirubin≥1.5xULN. 
• 
Obtain complete blood count with 
differential to assess eosinophilia. 
• 
Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G (or 
gamma globulins). 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease. Complete Liver 
Imaging and/or Liver Biopsy case report 
form if applicable 
• 
Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is 
not immediately available, discontinue study treatment for that subject if ALT ≥ 3xULN and bilirubin ≥ 
2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT ≥ 3xULN and bilirubin ≥ 2xULN (>35% direct bilirubin) or ALT ≥ 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury must be reported as a serious adverse event; INR 


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measurement is not required and the threshold value stated will not apply to subjects receiving 
anticoagulants 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, 
rash or eosinophilia).  Record the appearance or worsening of any such clinical symptoms on the adverse 
event report form. 
 
Table 4 Liver Chemistry Increased Monitoring Criteria 
Criteria 
Actions 
ALT ≥5xULN and <8xULN and bilirubin 
<2xULN without symptoms believed 
to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for >2 weeks. 
• 
Notify the medical monitor within 24 hours of 
learning of the abnormality to discuss subject 
safety.  
• 
Subject can continue study treatment   
• 
Subject must return weekly for repeat liver 
chemistries (ALT, aspartate aminotransferase, 
alkaline phosphatase, bilirubin) until resolution, 
stabilisation (ALT <5×ULN on 2 consecutive 
evaluations) or return to within baseline   
• 
If at any time subject meets the liver chemistry 
stopping criteria, proceed as described above 
 
Liver Safety- Study Treatment Restart 
 
Participants who meet liver stopping criteria for any reason will be discontinued from study treatment 
and permanently withdrawn from this clinical trial. 
 
 
Suicidal Risk Monitoring 
 
Subjects with HIV infection may occasionally present with symptoms of depression and/or suicidality 
(suicidal ideation or behaviour). In addition, there have been some reports of depression, suicidal 
ideation and behaviour (particularly in patients with a pre-existing history of depression or psychiatric 
illness) in some patients being treated with integrase inhibitors, including DTG. Therefore, it is 
appropriate to monitor subjects for suicidality before and during treatment.  
 
Subjects should be monitored appropriately and observed closely for suicidal ideation and behaviour, or 
any other unusual changes in behaviour. It is recommended that the investigator consider mental health 
consultation or referral for subjects who experience signs of suicidal ideation or behaviour. 
 
Assessment of treatment-emergent suicidality will be monitored during this study using the paper 
version of the Columbia Suicidality Severity Rating Scale (C-SSRS). The definitions of behavioral suicidal 
events used in this scale are based on those used in the Columbia Suicide History Form [21].  Questions 
are asked on suicidal behavior, suicidal ideation, and intensity of ideation.  Day 1 (Baseline) visit 
questions will be in relation to lifetime experiences and current experiences (within the past 2 months); 
all subsequent questioning is in relation to the last assessment. The C-SSRS is to be administered as a 
patient completed questionnaire specified in the Study Procedures Table (Appendix 1). The C-SSRS will 
be conducted manually with participants completing a paper survey. Additionally, the investigator will 


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collect and document information regarding any subject that experiences a possible suicidality-related 
AE (PSRAE) while participating in this study.   
 
If any subject experiences a PSRAE while participating in this study that is considered by the Investigator 
to meet ICH E2A [22] definitions for seriousness, the Investigator will collect information using a PSRAE 
CRF (or agreed alternative) in addition to reporting the event on a SAE CRF. A PSRAE may include, but is 
not limited to, an event that involves suicidal ideation, a preparatory act toward imminent suicidal 
behaviour, a suicide attempt, or a completed suicide.  The investigator will exercise his or her medical 
and scientific judgment in deciding whether an event is possibly suicide-related. PSRAE forms should be 
completed and reported to the GSK/ViiV safety team within one week of the investigator diagnosing a 
possible suicidality-related serious adverse event. 
 
Management of patients with significant renal toxicity  
 
Treatment with DTG/3TC must be discontinued in any subject developing moderate to severe renal 
impairment during the study, as indicated by confirmed creatinine clearance measuring <50 mL/min via 
the Cockcroft-Gault method (initial abnormal value must be confirmed by a repeat creatinine clearance 
assessment within 2 weeks.)  These participants will be permanently withdrawn from the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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9. Data Management 
• 
For this study, subject data will be entered into OIC defined CRFs, and will be maintained on a 
secure internal server at the study site. 
• 
Management of clinical data will be performed in accordance with applicable GCP standards and 
data cleaning procedures to ensure the integrity of the data, e.g., removing errors and 
inconsistencies in the data. 
• 
CRFs (including queries and audit trails) will be retained by Orlando Immunology Center, and 
deidentified copies can be sent upon request to ViiV/GSK for verification and review. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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10. Statistical Considerations and Data Analyses 
 
a. Analysis Objectives  
The primary objective of this study is to evaluate the efficacy of switching from B/F/TAF to DTG/3TC 
versus continuing the baseline regimen of B/F/TAF in HIV-infected, virologically suppressed adults as 
determined by the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48. 
The secondary objectives of this study are 
1. To evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion 
of participants with HIV-1 RNA≥50 copies/mL at Weeks 12 and 24 
2. To evaluate the efficacy of switching to DTG/3TC from B/F/TAF as determined by the proportion 
of participants with HIV-1 RNA<50 copies/mL at Weeks 12, 24 and 48 
3. To evaluate the safety, and tolerability of switching to DTG/3TC from B/F/TAF in HIV-infected, 
virologically suppressed adults through Week 48 
 
Primary Endpoint 
The primary efficacy endpoint is: 
• 
The proportion of participants with HIV-1 RNA≥50 copies/mL at Week 48 as defined by the US 
FDA-defined snapshot algorithm 
 
Secondary Endpoint 
The secondary efficacy endpoints are:  
• 
The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Weeks 12 and 24 as defined by 
the US FDA-defined snapshot algorithm 
• 
The proportion of participants with HIV-1 RNA <50 copies/mL at Weeks 12, 24 and 48 as defined 
by the US FDA-defined snapshot algorithm 
• 
The change from baseline in CD4+ cell count at Weeks 12, 24 and 48 
 
 
b. Demographic Data and Baseline Characteristics 
Demographic and baseline characteristics will be summarized using standard descriptive methods, 
including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for continuous variables, and 
frequency and percentages for categorical variables.  
Demographic data will include sex, race, ethnicity, age, and gender identity.  
Baseline characteristics including body weight, height, BMI, GFR, HIV-1 infection, and enrollment 
distribution will be summarized.  
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel test will be 
used to compare treatment groups. For continuous demographic and baseline characteristics, the 
Wilcoxon rank sum test will be used to compare treatment groups. 


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c. Efficacy Analysis 
The primary analysis will consist of a non-inferiority test of switching to DTG/3TC versus staying on 
B/F/TAF with respect to the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48, as 
defined by the US FDA-defined snapshot algorithm. The primary analysis of the efficacy endpoint will be 
based on the full data set (to include all patients in the study). 
US FDA-defined Snapshot Algorithm: All HIV-1 RNA data collected on-treatment (ie, including data 
collected up to 1 day after the last dose date of study drug) will be used in the snapshot algorithm.  
Virologic outcome will be defined as the following categories:  
• 
HIV-1 RNA ≥ 50 copies/mL: this includes participants a) Who have the last available on-
treatment HIV-1 RNA ≥ 50 copies/mL in the Week 48 analysis window, or b) Who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window and 1. Who 
discontinue study treatment prior to or in the Week 48 analysis window due to lack of 
efficacy, or 2. Who discontinue study treatment prior to or in the Week 48 analysis 
window due to reason other than lack of efficacy and have the last available on-
treatment HIV-1 RNA ≥50 copies/mL 
• 
HIV-1 RNA < 50 copies/mL: this includes participants who have the last available on-
treatment HIV-1 RNA < 50 copies/mL in the Week 48 window 
 
Analysis of Primary Efficacy Endpoint 
The null hypothesis is that the proportion of participants achieving HIV-1 RNA ≥ 50 copies/mL (as 
defined by the US FDA-defined snapshot algorithm) at Week 48 in DTG/3TC is at least 6% lower than the 
response rate in the B/F/TAF arm; the alternative hypothesis is that the response rate in the DTG/3TC 
arm is less than 6% lower than that in the B/F/TAF arm. Non-inferiority will be assessed using the 
conventional confidence interval (CI) approach. The point estimate of treatment difference (DTG/3TC–
B/F/TAF) and the associated 2-sided 95% CI will be constructed based on the exact method. 
It will be concluded that DTG/3TC is non-inferior to B/F/TAF if the upper bound of the 2-sided 95% CI of 
the difference between treatment groups [DTG/3TC –B/F/TAF] in the percentage of participants with 
HIV-1 RNA ≥50 copies/mL is less than 6% (i.e., a margin of 6% is applied to non-inferiority assessment).  
Secondary Analyses  
The proportion of participants with HIV-1 RNA≥ 50 copies/mL at Weeks 12 and 24, and the proportion of 
participants with HIV-1 RNA< 50 copies/mL at Weeks 12, 24 and 48 as defined by the US FDA-defined 
snapshot algorithm will also be summarized.  
The changes from baseline in CD4+ cell count at Weeks 12, 24 and 48 will be summarized by treatment 
using descriptive statistics. The differences between treatment groups at Week 48 and the associated 
95% CIs will be constructed using an Analysis of Variance (ANOVA) model, including treatment (DTG/3TC 
vs. B/F/TAF) as a fixed effect in the model. 
 
d. Safety Analysis  


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All safety data collected on or after the date that the study treatment was first administered up to the 
date of the last dose of study treatment will be summarized for participants in the safety analysis set 
according to the study treatment received 
Adverse Events 
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event with onset date on or after the study treatment start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to study 
drug discontinuation. Summaries (number and percentage of participants) of treatment-emergent 
adverse events will be provided by treatment. Additional summaries will include summaries for adverse 
events by grade, Investigator’s assessment of relationship to study treatment, and effect on study 
dosing.  
Laboratory Evaluations  
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute values and changes from baseline at all scheduled visits will be summarized.  
 
e. Patient Reported Outcomes (PRO)  
The PRO measures based on questionnaires will be summarized by treatment and visit using descriptive 
statistics. 
 
f. Sample Size Calculation 
Sample Size Sample sizes of 148 in DTG/3TC switch arm and 74 in the B/F/TAF arm achieve 
approximately 80% power to detect a non-inferiority margin difference between the group proportions 
of 0.06 for HIV-1 RNA <50 copies/mL at Week 48. The power is computed for the case when the actual 
treatment group difference is zero (treatment = reference). The test statistic used is the one-sided Score 
test (Farrington & Manning) with the significance level of 0.025. 
 
g. Analysis Schedule  
The Week 48 analyses will be conducted after all participants either complete their Week 48 visits or 
prematurely discontinue from the study treatment, respectively.  
 
 
 
 
 
 


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11. Study Governance and Considerations 
 
 
a. Posting of Information on Publicly Available Clinical Trial Registers 
 
Study information from this protocol will be posted on publicly available clinical trial registers before 
enrollment of subjects begins. 
 
 
b. Regulatory and Ethical Considerations, Including the Informed Consent 
 
Process 
 
Prior to initiation of the study, Orlando Immunology Center will obtain favorable opinion/approval from 
the appropriate regulatory agency to conduct the study in accordance with ICH Good Clinical Practice 
(GCP) and applicable country-specific regulatory requirements.  
 
The study will be conducted in accordance with all applicable regulatory requirements, and with 
Orlando Immunology Center Standard of Operating Procedures (SOP). The study will also be conducted 
in accordance with ICH Good Clinical Practice (GCP), all applicable subject privacy requirements, and the 
guiding principles of the current version of the Declaration of Helsinki.   
 
This includes, but is not limited to, the following: 
 
• 
IRB review and favorable opinion/approval of the study protocol and amendments as applicable 
• 
Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol deviations to IRB) 
• 
Signed informed consent must be obtained for each subject prior to participation in the study  
 
 
 
c. Quality Control (Study Monitoring) 
 
In accordance with applicable regulations including GCP, and Orlando Immunology Center procedures, 
the study principal investigator will meet with the study team prior to the start of the study to review 
with the site staff the protocol, study requirements, and their responsibilities to satisfy regulatory, 
ethical, and OIC requirements. 
 
• 
When reviewing data collection procedures, the discussion will also include identification, 
agreement and documentation of data items for which the OIC CRF will serve as the source 
document.  
 
The OIC will appoint a senior member of the research department who is not affiliated with the study to 
monitor the study and site activity to verify that the: 
• 
Data are authentic, accurate, and complete. 
• 
Safety and rights of subjects are being protected. 
• 
Study is conducted in accordance with the currently approved protocol and any other study 
agreements, GCP, and all applicable regulatory requirements.  
 
The investigator and the head of the medical institution (where applicable) agrees to allow the monitor 
direct access to all relevant documents 


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d. Quality Assurance 
 
• 
To ensure compliance with GCP and all applicable regulatory requirements, the study funder 
ViiV Healthcare may conduct a quality assurance assessment and/or audit of the site records, 
and the regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
• 
In the event of an assessment, audit or inspection, the investigator (and institution) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and to 
allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
 
 
e. Study and Site Closure 
 
• 
Upon completion or premature discontinuation of the study, the OIC monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with applicable 
regulations including GCP, and OIC SOP. 
• 
OIC reserves the right to temporarily suspend or prematurely discontinue this study at any time 
for reasons including, but not limited to, safety or ethical issues or severe non-compliance.  
• 
If the study is suspended or prematurely discontinued for safety reasons, OIC will promptly 
inform all investigators, the study funder (ViiV/GSK) and the relevant regulatory authorities of 
the suspension or premature discontinuation of the study and the reason(s) for the action. 
• 
If required by applicable regulations, the investigator or the head of the medical institution 
(where applicable) must inform the IRB promptly and provide the reason for the suspension or 
premature discontinuation. 
 
 
f. Records Retention 
 
• 
Following closure of the study, the investigator or the head of the medical institution (where 
applicable) must maintain all site study records (except for those required by local regulations to 
be maintained elsewhere), in a safe and secure location. 
• 
The records must be maintained to allow easy and timely retrieval, when needed (e.g., for a 
ViiV/GSK audit or regulatory inspection) and must be available for review in conjunction with 
assessment of the facility, supporting systems, and relevant site staff. 
• 
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g., microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  
• 
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions. 
• 
The Investigator’s Site Files must be retained for 5 years from the date of the final clinical study 
report or publication, unless local regulations or institutional policies require a longer retention 
period. No records may be destroyed during the retention period without the written approval 


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of the sponsor. 
 
• 
The investigator must notify ViiV/GSK of any changes in the archival arrangements, including, 
but not limited to, archival at an off-site facility or transfer of ownership of the records in the 
event the investigator is no longer associated with the site. 
 
 
g. Provision of Study Results, Posting of Information on Publicly Available 
 
Clinical Trials Registers and Publication 
 
No summaries of the study data according to actual randomized treatment groups will be available prior 
to the planned Week 24 preliminary analysis. Public presentation of the Week 24 analysis may be done 
prior to last subject’s week 48 visit. The investigator is encouraged to share the summary results with 
the study subjects, as appropriate. The procedures and timing for public disclosure of the results 
summary and for development of a manuscript for publication will be in accordance to the following 
timeline: 
 
Study Approval, IRB processing and final contracts/budgeting: 6 months (January 2020 -June 2020) 
 
Enrollment period and data collection: 18 months (July 2020-January 2022) 
 
Data Collation and analysis of Results: 4 months (January 2022-May 2022) 
 
IDWeek Abstract Preparation and Submission: 2 months (May 2022) 
 
IDWeek Abstract Presentation: October 2022 
 
Manuscript preparation and submission: 4 months: Target date October 2022 (post IDWeek) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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12. References 
 
1. 
Cahn, P., et al., Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil 
fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and 
GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, 
phase 3 trials. Lancet, 2019. 393(10167): p. 143-155. 
2. 
Cahn, P., et al., Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral 
treatment-naïve adults with HIV-1 infection - 96-week results from the GEMINI studies. 
Presented at the 10th International AIDS Conference on HIV Science (IAS 2019), 21-24th July 
2019, Mexico City, Mexico., 2019. 
3. 
Joly, V., et al., Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically 
suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother, 2019. 
74(3): p. 739-745. 
4. 
Corado, K.C., M.R. Caplan, and E.S. Daar, Two-drug regimens for treatment of naive HIV-1 
infection and as maintenance therapy. Drug Des Devel Ther, 2018. 12: p. 3731-3740. 
5. 
Hidalgo-Tenorio, C., et al., DOLAMA study: Effectiveness, safety and pharmacoeconomic analysis 
of dual therapy with dolutegravir and lamivudine in virologically suppressed HIV-1 patients. 
Medicine (Baltimore), 2019. 98(32): p. e16813. 
6. 
Baldin, G., et al., Long term data on the efficacy and tolerability of lamivudine plus dolutegravir 
as a switch strategy in a multicenter cohort of HIV1-infected, virologically suppressed patients. 
Int J Antimicrob Agents, 2019. 
7. 
Maggiolo, F., et al., Lamivudine/dolutegravir dual therapy in HIV-infected, virologically 
suppressed patients. BMC Infect Dis, 2017. 17(1): p. 215. 
8. 
Borghetti, A., et al., Efficacy and tolerability of lamivudine plus dolutegravir compared with 
lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a 
retrospective study from the clinical practice. BMC Infect Dis, 2019. 19(1): p. 59. 
9. 
Van Wyk, J., et al., Switching to DTG/3TC fixed dose combination (FDC) is non-inferior to 
continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 24 weeks 
(TANGO study).  Presented at the 10th International AIDS Conference for HIV Science (IAS 2019), 
21-24 July 2019, Mexico City, Mexico., 2019. 
10. 
Daar, E.S., et al., Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and 
tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically 
suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 
3, non-inferiority trial. Lancet HIV, 2018. 5(7): p. e347-e356. 
11. 
Molina, J.M., et al., Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide 
from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 
week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-
inferiority trial. Lancet HIV, 2018. 5(7): p. e357-e365. 
12. 
Wohl, D., et al., Patient-Reported Symptoms Over 48 Weeks Among Participants in 
 
Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-
 
formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Co-formulated 
 
Abacavir, Dolutegravir, and Lamivudine. Patient, 2018. 11(5): p. 561-573. 
13. 
Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
 
Agents in Adults and Adolescents Living with HIV.  2018:298 
14.  
Dovato Package Insert USPI.  ViiV Healthcare.  2020. 
15. 
Selik RM, Mokotoff ED, Branson B, Owen SM, Whitmore S, Hall HI. Morbidity and Mortality 
 
Weekly Report (MMWR). Revised Surveillance Case Definition for HIV Infection -United States 


Orlando Immunology Center (OIC)_008 
 
CONFIDENTIAL 
 
56 
 
 
2014. Centers for Disease Control and Prevention, 2014. 
16.  
Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85. 
17. 
Wensing AM., Calvez V., Ceccherini-Silberstein F., et al., 2019 Update of the Drug Resistance 
 
Mutations in HIV-1.  Top Antivir Med . 2019 Sep;27(3):111-121. 
18. 
Biktarvy Package Insert USPI.  Gilead Sciences.  2019. 
19.  
FDA Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation. July 
 
2009. Accessed 07 January 2015 at: 
 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022145s032,203045s010,205
 
786s001lbl.pdf 
20.  
U.S. Department of Health and Human Services, National Institutes of Health, National 
 
Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for 
 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. 
 
Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
21. 
Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of 
 
Suicide Assessment (C-CASA): classification of suicidal events in the FDA’s pediatric suicidal risk 
 
analysis of antidepressants. Am J Psychiatry. 2007;164:1035–43. 
22.  
International Conference on Harmonization of Technical Requirements for Registration of  
 
Pharmaceuticals For Human Use. ICH Harmonized Tripartite Guideline. Clinical safety data 
 
management: Definitions and standards for expedited reporting. ICH E2A. 1994 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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13. Appendices 
 
Appendix 1. Study Procedures Table 
 
 
Study Procedure 
Screening 
Day 1 
Week 
1 
(Phone 
Call) 
Week 4 
Week 
12 
Week 
24 
Week 
36 
(Phone 
Call)c 
Week 
48a 
Informed Consent 
X 
 
 
 
 
 
 
 
HIV Symptoms Distress Module 
 
X 
 
X 
X 
X 
 
X 
HIV-TSQ 
 
X 
 
X 
X 
X 
 
X 
Vas Adherence Questionnaire  
 
X 
 
X 
X 
X 
 
X 
C-SSRS 
 
X 
 
X 
X 
X 
 
X 
Medical History 
X 
 
X 
 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Complete/Symptom-Directed 
Physical Exam 
X 
X 
 
X 
X 
X 
 
X 
Height 
X 
 
 
 
 
 
 
 
Weight/Waist Circumference 
X 
X 
 
X 
X 
X 
 
X 
Vital Signs 
X 
X 
 
X 
X 
X 
 
X 
Urine Pregnancy Testb 
 
X 
 
X 
X 
X 
X 
X 
Serum Pregnancy Testb 
X 
 
 
 
 
 
 
 
FSH Test 
X 
 
 
 
 
 
 
 
Chemistry Profile 
X 
 
 
X 
X 
X 
X 
X 
Metabolic Assessments 
X 
 
 
 
 
X 
 
X 
Hematology Profile 
X 
 
 
X 
X 
X 
X 
X 
Plasma HIV-1 RNA 
X 
 
 
X 
X 
X 
X 
X 
CD4+ Cell Count and Percentage 
X 
 
 
 
 
X 
X 
X 
Urinalysis 
X 
 
 
X 
X 
X 
X 
X 
HBV Blood Panel 
X 
 
 
 
 
X 
 
X 
HCV Serology 
X 
 
 
 
 
X 
 
X 
HIV-1 Genotype 
 
 
 
 
 
 
 
 
Obtain Screening number 
X 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
aProcedures at Withdrawal visit are identical to those at Week 48 
bPerformed in females of child-bearing potential 
cParticipants will present to the research center for laboratory assessments only 


 
 
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Appendix 2. Pregnancy Precautions, Definition for Persons of Childbearing Potential, and 
Contraceptive Requirements 
 
1) Definitions  
 
a. Definition of Childbearing Potential  
 
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.   
 
Women are considered to be in a postmenopausal state when they are >54 years of age with 
cessation of previously occurring menses for >12 months without an alternative cause. In addition, 
women < 54 years of age with amenorrhea of ≥ 12 months may also be considered 
postmenopausal if their FSH level is in the postmenopausal range, and they are not using 
hormonal contraception or hormonal replacement therapy.  
 
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy 
in a female participant of any age.  
 
b. Definition of Male Fertility  
 
For the purposes of this study, a male born participant is considered to be fertile after the 
initiation of puberty unless permanently sterile by bilateral orchiectomy or medical 
documentation.  
 
2) Contraception Requirements for Persons of Childbearing Potential  
 
The inclusion of persons of childbearing potential requires the use of highly effective contraceptive 
measures.  They must have a negative serum pregnancy test at Screening and a negative 
pregnancy test on the Baseline/Day 1 visit prior to randomization.  In the event of a delayed 
menstrual period (over one month between menstruations), a pregnancy test must be performed 
to rule out pregnancy.  This is true even for persons of childbearing potential with infrequent or 
irregular periods.  Female participants must also agree to one of the following from Screening until 
30 days after the last dose of study drug. 
 
• 
Complete abstinence from intercourse of reproductive potential.  Abstinence is an 
acceptable method of contraception only when it is in line with the participant’s preferred 
and usual lifestyle.  
Or 
 
• 
Consistent and correct use of 1 of the following methods of birth control listed below. 
o Intrauterine device (IUD) with a failure rate of <1% per year 
o Intrauterine hormone-releasing system (IUS) with a failure rate of <1% per 
year 
o Tubal sterilization 
o Essure micro-insert system (provided confirmation of success by 
hysterosalpingogram three months after procedure and where permitted 
and used per local prescribing label) 


 
 
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o Vasectomy in the male partner (provided that the partner is the sole 
sexual partner and had confirmation of surgical success 3 months after 
procedure)  
 
Persons of childbearing potential who wish to use a hormonally based contraceptive method must 
use it in conjunction with a barrier method, preferably a male condom.  Persons of childbearing 
potential who utilize a hormonal contraceptive as one of their birth control methods must have 
consistently used the same method for at least three months prior to study dosing.   Hormonally 
based contraceptives and barrier methods permitted for use in this protocol are as follows: 
 
• 
Barrier methods (each method must be used with a hormonal method) 
o Male condom (with or without spermicide) 
o Female condom (with or without spermicide) 
o Diaphragm with spermicide 
o Cervical cap with spermicide 
o Sponge with spermicide 
 
• 
Hormonal methods (each method must be used with a barrier method, preferably male 
condom) 
o Oral contraceptives (either combined or progesterone only) 
o Injectable progesterone 
o Subdermal contraceptive implant 
o Transdermal contraceptive patch 
o Contraceptive vaginal ring  
 
Persons of childbearing potential must also refrain from egg donation and in vitro fertilization 
during treatment and until at least 30 days after the end of relevant systemic exposure.  
 
3) Contraception Requirements for Male Participants  
 
During the study, male participants should use condoms when engaging in intercourse of 
reproductive potential with persons of childbearing potential. 
 
4) Unacceptable Contraceptive Methods  
Contraceptive methods that are unacceptable include periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM).  Female condom and male condom should not 
be used together.   
 
5) Procedures to be Followed in the Event of Pregnancy  
 
Participants will be instructed to notify the investigator if they become pregnant, or are concerned 
they may be pregnant, at any time during the study, or if they become pregnant within 30 days of 
last study drug dose. Participants who become pregnant or who suspect that they are pregnant 
during the study must report the information to the investigator and discontinue study drug 
immediately. 
 
Participants who become pregnant while on study should receive appropriate monitoring and care 
until the conclusion of the pregnancy. Subjects who become pregnant while on study who are not 


 
 
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engaged in pre-natal care that includes a routine second trimester ultrasound will be referred for 
ultrasonography as part of study follow-up. Instructions for reporting pregnancy and pregnancy 
outcomes are outlined in Section 8f.