An Open-label, Single Arm Study to Evaluate the Week 48 Efficacy and Safety of a Two-drug Regimen of Dolutegravir/Lamivudine (DTG/3TC) as a Fixed Dose Combination (FDC), in Antiretroviral Therapy (ART)-Naive HIV-1-infected Adolescents, ≥12 to <18 Years of Age Who Weigh at Least 25 kg
Phase: PHASE3
Conditions: HIV Infections
Sponsor: ViiV Healthcare

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 3
20-Nov-2020
2017N326062_03
Amendment 2
13-Nov-2019
2017N326062_02
Amendment 1
13-Jun-2018
2017N326062_01
Original Protocol
04-Apr-2018
2017N326062_00
Amendment 3: 20-NOV-2020
Overall Rationale for the Amendment:
Guidance for the management of decline in renal function was modified to incorporate instruction 
based on change from baseline in DAIDS AE severity grading (Grades 1- 4) for serum creatinine 
and eGFR (further clarification of how to determine creatinine and eGFR grade is also provided). 
These modifications were made to clarify and simplify participant management. It incorporates 
stepwise instruction, based on severity grade, for confirmatory testing and assessment, and 
parameters for temporary holding or permanent discontinuation of study treatment. Further 
specific guidance on additional investigations that may be required and the need for consultation 
with the study Medical Monitor regarding further follow-up and management has also been 
incorporated. An existing protocol exclusion criterion excludes participants with creatinine 
clearance of <50 mL/min/1.73 m2 and allows for potential enrollment of participants with a baseline 
Grade 3 creatinine clearance, 51-59 mL/min/1.73 m2 (DAIDS Table for AE Severity Grading Grade 
3 creatinine clearance parameters are <60 to 30 mL/min/1.73 m2). Therefore, using a change from 
baseline in severity grading to take action also provides further clarification for participant 
management. 
Section # and Name
Description of Change
Brief Rationale
Medical Monitor/SAE 
Contact Information 
•
Contacts updated
•
Contacts updated to align
with team member
changes
Summary Section 1 
and 5.2 Number of 
Participants
•
Number of screened subjects
increased from approximately
40 to approximately 80
•
Update made due to
screen fail rate
Section 2 Schedule of 
Activities
•
Corrected typos and updated
abbreviations
•
To improve quality of the
protocol
Section 3.1 Study 
Rationale
•
Included approval of Dovato in
multiple countries
•
Updated to align with
current approvals

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Section # and Name
Description of Change
Brief Rationale
Section 3.3.1 Risk 
Assessment
•
Removed reference to TDF and
FTC
•
Removed reported risk
associated with the use of TDF
in clinical practice
•
Updated exclusionary language
•
Updated risk of neural tube
defect to reflect current data
(change in rate from 0.3% to
0.19).
•
Clarified how renal function will
be monitored
•
Risk mitigation strategy
related to renal function
(Section 3.3.1) was
updated to align with
changes applied in Section
12.9.1.3 (Decline in Renal
Function).
•
Recent data from
surveillance study in
Botswana added for
completeness.
Section 7.9 
Concomitant Therapy
•
Added COVID-19 treatment and
drug interaction guidance
•
Clarified to consult with
Study Medical Monitor to
evaluate appropriate
options and whether study
participation remains
appropriate.
Section 8.2 Withdrawal 
from the Study and 
Stopping Criteria and 
12.4.3 Informed 
Consent and Assent 
Process
•
Added instruction on how to
manage participants who have
a guardianship status change
such that they become a ward
of State during the study
•
This modification was
made to clarify and simplify
participant management
Sections 9.3.2, 12.8.6 
and 12.10.2
Pregnancy
•
Updated pregnancy reporting
timeframes from 2 weeks to 24
hours
•
To align with current
pregnancy notification
timelines
Section 9.4 Treatment 
of Overdose
•
Added reference for intentional
overdose
•
Added a reference to
Section 9.3.4 which
provides additional
instruction
Section 9.6.1.1 
Collection of Sparse 
PK Samples
•
Added collection timeframe post
previous dose
•
Clarified the pre-dose
samples should be
collected 20-28 hours post
previous dose
Section 10.3.4 Other 
Analyses
•
Added special statistical and
data analysis may be warranted
•
These may be warranted in
the event COVID-19,
related epidemics or
natural disasters that may
affect the study

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Section # and Name
Description of Change
Brief Rationale
Section 11 References
•
Added DTG Investigator’s
Brochure versions 13 and 14
•
Updated references
•
Added DTG Investigator’s
Brochure (IB) version
updates for completeness
•
Updated references to
align with amendment
modifications for
completeness.
Section 12.4.3 
Informed Consent and 
Assent Process
•
Added instruction on how to
manage participants who have
a guardianship status change
such that they become a ward
of the state during the study
•
This modification was
made to clarify and simplify
participant management
Section 12.7 Appendix 
7 
Laboratory/Chemistries 
Table
•
Added instruction to use
absolute value for creatinine
and creatinine clearance to
determine severity grade
•
For clarity, added
reference to Section
12.9.1.3  for details on
toxicity management
Section 12.8.7 
Appendix Reporting 
COVID-19 AEs and 
SAEs
•
Added section for reporting
COVID-19 AEs and SAEs
•
To provide guidance on the
reporting of COVID-19
specific AEs and SAEs
Section 12.9 Appendix 
9: Toxicity 
Management
•
Added reference for general
guidelines on the management
of specific toxicities
•
For clarity, added cross
reference to Section 12.9.1
for general guidelines on
the management of
specific toxicities
Section 12.9.1.3 
Appendix Decline in 
Renal Function
•
Modified to incorporate
instruction based on change
from baseline in DAIDS AE
severity grading (Grades 1- 4)
for serum creatinine and eGFR
(with further clarification of how
to determine creatinine and
eGFR grade) and guidance on
further
investigations/discussions
required for appropriate patients
and the need for timely
confirmatory testing.
•
This modification was
made to clarify and simplify
participant management
Section 12.12 
Appendix 12: COVID-
19 Guidance
•
Added COVID-19 guidance
•
This modification was
made to provide COVID-19
participant management

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Section # and Name
Description of Change
Brief Rationale
Throughout
•
Incorporated minor
clarifications, updated links and
abbreviations and corrected
typos
•
To improve quality of the
protocol

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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................4
1.
SUMMARY.............................................................................................................12
2.
SCHEDULE OF ACTIVITIES (SOA).......................................................................14
3.
INTRODUCTION....................................................................................................22
3.1.
Study Rationale ..........................................................................................22
3.2.
Background ................................................................................................23
3.3.
Benefit/Risk Assessment ............................................................................25
3.3.1.
Risk Assessment .........................................................................26
3.3.2.
Benefit Assessment.....................................................................30
3.3.3.
Overall Benefit:Risk Conclusion...................................................30
4.
OBJECTIVES AND ENDPOINTS...........................................................................30
5.
STUDY DESIGN ....................................................................................................31
5.1.
Overall Design ............................................................................................31
5.2.
Number of Participants ...............................................................................32
5.3.
Participant and Study Completion...............................................................33
5.4.
Scientific Rationale for Study Design ..........................................................33
5.5.
Dose Justification........................................................................................33
6.
STUDY POPULATION...........................................................................................34
6.1.
Inclusion Criteria.........................................................................................35
6.2.
Exclusion Criteria........................................................................................36
6.3.
Screen Failures...........................................................................................38
7.
TREATMENTS.......................................................................................................39
7.1.
Treatments Administered............................................................................39
7.2.
Dose Modification .......................................................................................39
7.3.
Treatment Assignment................................................................................39
7.4.
Blinding.......................................................................................................40
7.5.
Packing and Labeling .................................................................................40
7.6.
Preparation/Handling/Storage/Accountability..............................................40
7.7.
Compliance with Study Treatment Administration.......................................40
7.8.
Study Treatment Overdose.........................................................................41
7.9.
Concomitant Therapy..................................................................................41
7.9.1.
Permitted Medications and Non-Drug Therapies..........................41
7.9.2.
Prohibited Medications and Non-Drug Therapies.........................42
7.10.
Treatment after the End of the Study ..........................................................43
8.
DISCONTINUATION CRITERIA.............................................................................44
8.1.
Discontinuation of Study Treatment ............................................................44
8.1.1.
Virologic Criteria for Withdrawal, Participant Management 
and Viral Resistance Testing .......................................................44
8.1.1.1.
Virologic Withdrawal Criteria.......................................44
8.1.1.2.
Managing Participants Meeting Suspected 
Virologic Withdrawal Criteria.......................................45

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8.1.1.3.
Managing Participants Meeting Confirmed 
Virologic Withdrawal Criteria.......................................45
8.1.2.
Liver Chemistry Stopping Criteria ................................................46
8.1.3.
Temporary Discontinuation of Study Treatment ...........................47
8.1.4.
Study Treatment Restart or Rechallenge .....................................48
8.2.
Withdrawal from the Study and Stopping Criteria........................................48
8.3.
Lost to Follow Up........................................................................................49
9.
STUDY ASSESSMENTS AND PROCEDURES .....................................................50
9.1.
Screening and Critical Baseline Assessments ............................................50
9.1.1.
Screening Assessments ..............................................................50
9.1.2.
Baseline Assessments.................................................................52
9.2.
Efficacy Assessments.................................................................................52
9.3.
Safety Assessments ...................................................................................53
9.3.1.
Adverse Events and Serious Adverse Events..............................53
9.3.1.1.
Time Period and Frequency for Collecting AE 
and SAE Information ..................................................53
9.3.1.2.
Method of Detecting AEs and SAEs ...........................54
9.3.1.3.
Follow-up of AEs and SAEs........................................54
9.3.1.4.
Cardiovascular and Death Events ..............................54
9.3.1.5.
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................54
9.3.1.6.
Regulatory Reporting Requirements for SAEs............55
9.3.2.
Pregnancy ...................................................................................55
9.3.3.
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs...............................................56
9.3.4.
Suicidal Risk Monitoring...............................................................56
9.4.
Treatment of Overdose...............................................................................57
9.4.1.
Physical Examinations.................................................................58
9.4.2.
Electrocardiograms......................................................................58
9.4.3.
Clinical Safety Laboratory Assessments ......................................58
9.5.
Viral Genotyping and Phenotyping..............................................................60
9.5.1.
HIV-1 Polymerase Viral Genotyping and Phenotyping .................60
9.5.2.
HIV-1 Exploratory Analyses .........................................................60
9.6.
Pharmacokinetics .......................................................................................61
9.6.1.
Blood Sample Collection..............................................................61
9.6.1.1.
Collection of Sparse PK samples – All 
Participants ................................................................61
9.6.1.2.
Collection of Ctrough samples- All Participants ..........61
9.6.2.
Important Information on collection of PK samples ......................62
9.6.2.1.
Timing of sparse PK sample collection .......................62
9.6.2.2.
Dosing Diary Cards ....................................................62
9.6.2.3.
Collection of Intensive Serial PK samples...................62
9.6.3.
Sample Analysis ..........................................................................63
9.7.
Pharmacodynamics ....................................................................................63
9.8.
Genetics .....................................................................................................63
9.9.
Biomarkers .................................................................................................63
9.10.
Health Economics.......................................................................................63
10. STATISTICAL CONSIDERATIONS........................................................................63
10.1.
Sample Size Determination ........................................................................63
10.2.
Populations for Analyses ............................................................................64

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10.2.1.
Intent-to-Treat Exposed (ITT-E) Population .................................64
10.2.2.
Per Protocol (PP) Population .......................................................64
10.2.3.
Safety Population.........................................................................64
10.2.4.
Pharmacokinetic Populations.......................................................64
10.2.5.
Analysis Data Sets.......................................................................64
10.3.
Statistical Analyses.....................................................................................65
10.3.1.
Efficacy Analyses.........................................................................65
10.3.2.
Safety Analyses...........................................................................65
10.3.3.
Pharmacokinetic Analyses...........................................................66
10.3.3.1.
Intensive Pharmacokinetic Analyses ..........................66
10.3.3.2.
Sparse Pharmacokinetic Analysis...............................67
10.3.4.
Other Analyses ............................................................................67
10.3.5.
Secondary Analyses ....................................................................67
11. REFERENCES.......................................................................................................69
12. APPENDICES........................................................................................................73
12.1.
Appendix 1: Abbreviations and Trademarks................................................73
12.2.
Appendix 2: Child-Pugh Classification ........................................................76
12.3.
Appendix 3: Liver Safety Required Actions and Follow up 
Assessments ..............................................................................................77
12.4.
Appendix 4: Study Governance Considerations..........................................80
12.4.1.
Posting of Information on Publicly Available Clinical Trial 
Registers .....................................................................................80
12.4.2.
Regulatory and Ethical Considerations ........................................80
12.4.3.
Informed Consent and Assent Process........................................81
12.4.4.
Data Protection............................................................................82
12.4.5.
Independent Data Monitoring Committee.....................................82
12.4.6.
Dissemination and Publication of Clinical Study Data ..................83
12.4.6.1.
Dissemination of Study Data ......................................83
12.4.6.2.
Publication of Study Data ...........................................83
12.4.7.
Data Quality Assurance and Control............................................83
12.4.7.1.
Quality Assurance ......................................................83
12.4.7.2.
Quality Control............................................................84
12.4.8.
Source Documents and Retention ...............................................84
12.4.8.1.
Source Documents.....................................................84
12.4.8.2.
Records Retention......................................................85
12.4.9.
Study and Site Closure ................................................................85
12.5.
Appendix 5: Liver Safety – Study Treatment Restart or Rechallenge 
Guidelines...................................................................................................87
12.5.1.
Drug Rechallenge Following Liver Events that are 
Possibly Related to IP..................................................................87
12.5.2.
Drug Restart Following Transient Resolving Liver Events 
Not Related to IP .........................................................................88
12.6.
Appendix 6: CDC Classification and WHO Staging for HIV-1 
Infection......................................................................................................90
12.6.1.
CDC Classification for HIV-1 Infection .........................................90
12.6.2.
World Health Organization. WHO Classification of HIV-
Related Disease in Adults and Adolescents.................................92
12.7.
Appendix 7: Division of AIDS Table for Grading Severity of Adults 
and Pediatric Adverse Events.....................................................................94

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12.8.
Appendix 8: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................123
12.8.1.
Definition of AE..........................................................................123
12.8.2.
Definition of Serious Adverse Event...........................................124
12.8.3.
Definition of Cardiovascular Events ...........................................125
12.8.4.
Sentinel Events..........................................................................126
12.8.5.
Recording and Assessing AE and SAE......................................126
12.8.6.
Reporting of SAE to ViiV Healthcare/GSK/PPD .........................128
12.8.7.
Reporting COVID-19 AEs and SAEs..........................................130
12.9.
Appendix 9: Toxicity Management ............................................................131
12.9.1.
Specific Toxicities/Adverse Event Management.........................132
12.9.1.1.
Liver Chemistry Stopping and Follow-up 
Criteria......................................................................132
12.9.1.2.
Restarting Study Drug ..............................................133
12.9.1.3.
Decline in Renal Function.........................................133
12.9.1.4.
Allergic reaction........................................................134
12.9.1.5.
Rash.........................................................................134
12.9.1.6.
Hypertriglyceridemia/Hypercholesterolemia..............135
12.9.1.7.
Creatine Phosphokinase (CPK) Elevation ................135
12.10. Appendix 10: Modified List of Highly Effective Methods for Avoiding 
Pregnancy and Collection of Pregnancy Information.................................136
12.10.1. Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential (FRP) ............136
12.10.2. Collection of Pregnancy Information ..........................................136
12.11. Appendix 11: Decision Flow- Screening Tests for Hepatitis B Virus 
Serology, Interpretation and Action...........................................................138
12.12. Appendix 12: COVID-19 Guidance ...........................................................139
12.12.1. COVID -19 Experimental Agents ...............................................139
12.12.2. COVID-19 Specific Data Capture...............................................139
12.12.2.1. Capturing COVID-19 Specific Protocol 
Deviations ................................................................139
12.12.2.2. Capturing COVID-19 Specific AEs and SAEs...........139
12.13. Appendix 13: Protocol Amendment History...............................................142

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1.
SUMMARY
Protocol Title: An open-label, single arm study to evaluate the week 48 efficacy and 
safety of a two-drug regimen of dolutegravir/lamivudine (DTG/3TC) as a fixed dose 
combination (FDC), in antiretroviral therapy (ART)-naive HIV-1-infected adolescents, 
12 to <18 years of age who weigh at least 25 kg.
Short Title: An open label, single arm study of the safety and efficacy of DTG/3TC in 
therapy-naïve HIV-1 infected adolescents.
Rationale: Data from this adolescent trial is intended to supplement datasets from 
GEMINI-1 and GEMINI-2 studies (204861 and 205543), 2 large, global, randomized, 
double-blind, active controlled clinical trials of DTG plus 3TC in HIV-1 infected ART-
naïve adults. As such, data from this trial will provide ‘bridging’ information for 
regulatory authorities and treating clinicians. The dual combination of DTG plus 3TC is 
under assessment in pediatric participants 2 to <12 years of age in a separate study.
Objectives and Endpoints:
Objective
Endpoint
Primary

To assess the antiviral activity of DTG/3TC 
in antiretroviral naïve HIV-1 infected 
adolescents.

The proportion of participants with plasma 
HIV-1 RNA less than 50 c/mL at Week 48 
using the Snapshot algorithm (ITT-E 
population).
Secondary

To assess the early antiviral activity of 
DTG/3TC and to determine the extended 
long term (≥96 weeks) safety, tolerability, 
and viral response of DTG/3TC in 
antiretroviral naïve HIV-1 infected 
adolescents.

Proportion of participants with plasma HIV-
1 RNA <200 and <50 copies/mL at Week 
24, Week 96 and Week 144.

Proportion of participants with plasma HIV-
1 RNA <200 copies/mL at Week 48

Incidence and severity of AEs and 
laboratory abnormalities through 144 
weeks

Proportion of participants who discontinue 
treatment due to AEs through 144 weeks

Safety and tolerability assessments at 
Weeks 96 and 144.

Viral load monitoring after Week 48 
through Week 144.

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Objective
Endpoint

To evaluate the effect of DTG/3TC on 
immunologic response from baseline to 24 
and 48 weeks

Change from baseline in CD4+ and CD8+ 
cell count and ratio at Week 24 and 48.

Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome (AIDS), and 
death) through Weeks 24 and 48.

To assess the safety and tolerability of 
DTG/3TC in HIV-1 infected adolescents at 
24 and 48 weeks

Incidence and severity of AEs and 
laboratory abnormalities through 24 and 
48 weeks

Proportion of participants who discontinue 
treatment due to AEs through 24 and 48 
weeks

To assess DTG and 3TC exposure and to 
evaluate the steady-state 
pharmacokinetics of DTG and 3TC in HIV-
1 infected adolescents 

Steady-state plasma PK parameters of 
DTG and 3TC will be assessed using 
intensive PK collected in a subset of 
participants.

To assess development of viral resistance 
to DTG and 3TC in participants 
experiencing protocol-defined virologic 
failure (i.e. meeting confirmed virologic 
withdrawal criteria).

Incidence of observed genotypic and 
phenotypic resistance to DTG and 3TC for 
participants meeting confirmed virologic 
withdrawal criteria. 
Overall Design: This is an open label, single arm, 48-week assessment of the fixed dose 
combination of DTG/3TC in HIV-1 infected, antiretroviral naïve adolescents.
Number of Participants: This study will be conducted in approximately 30 HIV-1 
infected, treatment naïve adolescent participants with screening plasma HIV-1 RNA 
500,000 c/mL.  Approximately 80 participants will be screened to enable enrolment of 
approximately 30 participants.
Treatment Groups and Duration: All participants will receive the fixed dose 
combination of DTG/3TC (50/300 mg) for once daily dosing. After a Screening Period of 
up to 28 days, all participants will be treated for 48-week Treatment Phase.  Participants 
who successfully complete 48 weeks of therapy and who continue to receive benefit from 
this two-drug regimen may enter a 96-week study Extension Phase.  Participants who 
successfully complete the Extension Phase and who continue to receive benefit from this 
two-drug regimen will have access to this regimen in a Continuation Phase until it is 
available locally.
Analysis: The primary endpoint of the proportions of participants meeting the criteria for 
virologic success as defined by the US Food and Drug Administration (FDA) snapshot 
algorithm will be reported with exact Clopper Pearson 95% confidence intervals.  Safety 
analyses will be summarized by visit.

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2.
SCHEDULE OF ACTIVITIES (SOA)
Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
a Screening: Enrolment may occur as soon as all Screening results are available.
b Extension Phase: All participants who successfully complete treatment through Week 48 will have the opportunity to enter the Extension Phase.
c Continuation Phase: If required by local regulations, study participants who have successfully completed the study through Week 144 may enter the Continuation Phase, 
regardless of age, and will continue to receive DTG/3TC until it is available locally (See Section 7.10, Treatment after the End of the Study). Prior to transitioning to locally 
approved and available supply, the participant will return to complete a final End of Continuation Phase visit.
d Withdrawal: Participants will complete a Withdrawal visit at the time they withdraw from the study and will return for a follow-up visit 4 weeks after the last dose of study 
medication.
e Follow-up: An in-clinic Follow-Up visit will be conducted 4 weeks after the last dose of study medication upon withdrawal from study. A follow-up visit will not be applied 
for participants completing the End of Continuation Phase Visit, (as they will continue to receive DTG plus 3TC) or for participants who withdraw consent for further 
participation at the time of early withdrawal from the study.
Clinical and Other 
Assessments
Written informed consent 
and assent
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Assent will be obtained as 
appropriate according to local 
guidelines. Written informed 
consent must be obtained from the 
participant if he/she reaches the 
age of majority while on study.

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Inclusion and exclusion criteria
SC
B
.
.
.
.
.
.
.
.
.
.
.
.
.
Inclusion/exclusion criteria will be 
assessed fully at the Screening visit. 
Changes between the Screening visit 
and the Day 1 visit should be 
considered to ensure eligibility, 
including review of additional 
assessments performed at Day 1.
Demography 
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Including year of birth, sex, race, 
ethnicity.
Medical history 
(includes substance abuse)
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Full medical history will be conducted 
prior to enrollment and include 
assessments of cardiovascular, 
metabolic (e.g., Type I or II diabetes 
mellitus), psychiatric (e.g., depression), 
renal (e.g., nephrolithiasis, 
nephropathy, renal failure), and bone 
disorders.
Prior ART/PMTCT history, 
as applicable
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Tanner staging score 
B
.
.
.
.
.
.
.
48
E 
(Every 48 
Weeks)
.
.
.
.
Tanner scoring will be collected until 
the end of adolescence.  During the 
Extension Phase, assess Tanner 
Score only every 48 weeks.
Concurrent medical conditions
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Vital signs
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
HIV risk factors and 
mode of transmission
.
B
.
.
.
.
.
.
.
.
.
.
.
.
.
CDC or WHO HIV-1 
classification
SC
B
.
.
.
.
.
.
.
.
.
.
.
.
.
See Section 12.6, Appendix 6: CDC 
Classification and WHO Staging for 
HIV-1 Infection
HIV associated conditions
.
.
.
4
8
12
16
24
36
48
E
C
EC
W
.
Columbia Suicidality Rating 
Scale
.
B
.
4
8
12
16
24
36
48
E
C
EC
W
.
On Day 1, the electronic Columbia 
Suicidality Severity Rating Scale eC-
SSRS, (patient completed 
questionnaire) is to be administered 
prior to enrolment. 
CSSRS participant level reports should 
reviewed, signed by Investigator or 
Sub-Investigator and filed in site 
source. Actions taken for positive 
findings should be clearly documented.
Concomitant medication
SC
B
.
4
8
12
16
24
36
48
E
C
EC
W
F
Symptom directed physical 
examination/Medical decision-
making including height and 
weight
SC
B
.
4
8
12
16
24
36
48
E
.
W
F

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
12-lead ECG
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Perform 12-lead ECG after resting in a 
semi-supine position for at least 5 
minutes.
Adverse events
SC
B
4
8
12
16
24
36
48
E
C
EC
W
F
Only SAEs related to study 
participation or to a concomitantly 
administered ViiV 
Healthcare/GlaxoSmithKline (GSK) 
product will be collected between 
obtaining informed consent and 
administration of study drug at Day 1.
Serious adverse events
SC  
B
4
8
12
16
24
36
48
E
C
EC
W
F
Laboratory Assessments
Sites should make every effort to ship 
lab samples to Q2 on the same day as 
sample collection.
Plasma for HIV genotyping
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Quantitative plasma HIV-1 RNA
SC
B
.
4
8
12
16
24
36
48
E
C
EC
W
.
Lymphocyte subsets
SC
B
.
4
8
12
16
24
36
48
E  
.
.
W
.

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Plasma for storage
SC
B
.
4
8
12
16
24
36
48
E
C
EC
W
.
Plasma samples for storage will be 
collected at each visit starting at 
Screening, including any unscheduled 
visits.  These samples will be used 
when needed such as when samples 
are lost, arrive at the laboratory 
unevaluable, or for PK or genotypic 
and/or phenotypic analyses when 
participants meet Suspected and 
Confirmed Virologic Withdrawal 
criteria.
Clinical chemistry
SC
B
.
4
8
12
16
24
36
48
E
.
.
W
F
Hematology
SC
B
.
4
8
12
16
24
36
48
E
.
.
W
F
PT/INR
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Fasting lipids, glucose, HbA1c
.
B
.
.
.
.
.
24
48
E
.
.
W
.
An overnight fast is preferred; 
however, a minimum of a 6-hour fast is 
acceptable. During Extension Phase, 
collect fasting lipids, glucose, and 
glycated haemoglobin (Hb1Ac) only 
every 24 weeks.
Collect at Withdrawal only if withdrawal 
visit occurs at Weeks 48,96 or 144
Urinalysis and spot urine for 
protein analysis
.
B
.
.
.
12
.
24
.
48
E
.
.
W
F
A morning specimen is preferred

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Pregnancy test
SC 
(S)
B 
(U)
.
4 
(S)
8 
(S)
12 
(S)
16 
(S)
24 
(S)
36 
(S)
48 
(S)
E 
(S)
C 
(S)
EC
(S)
W 
(S)
.
Pregnancy testing will be conducted 
(females of reproductive potential only) 
on serum (S) samples with the 
exception of Day 1, which must be a 
urine (U) test to confirm status prior to 
administration of study treatment.
Remind females of reproductive 
potential of the need to avoid 
pregnancy while in study and 
adherence to the study’s contraception 
requirements.
HBsAg, anti-HBc, anti-HBs, 
and HBV DNA
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
HBV DNA testing will be performed for 
participants with positive anti-HBc and 
negative HBsAg and negative anti-HBs 
(past and/or current evidence).  
Participants will have to return to the 
clinic to provide a sample for HBV DNA 
testing prior to enrollment.
HCV antibody
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
RPR
SC
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Sample for Ctrough 
measurement
.
.
.
.
8
.
16
.
36
48
.
.
.
.
.

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Sample for pharmacokinetic 
analysis (sparse collection – all 
participants)
.
.
.
4
.
12
.
24
.
.
.
.
.
.
.
At each scheduled visit, collect a pre-
dose sample and a post dose sample 
as described in Section 9.6.1
Dispense PK Diary Card 
.
B
.
4
8
12
16
24
36
48
.
.
.
.
.
Participant to complete dosing diary for 
3 days prior to PK and Ctrough 
sampling visits. The PK visit should be 
re-scheduled if the participant took 
their morning dose prior to coming into 
the clinic on the sparse or intensive PK 
sampling day.  
Sample for pharmacokinetic 
analysis (intensive serial 
collection – subset of 
participants)
.
.
1
.
.
.
.
.
.
.
.
.
.
.
.
To be collected in a subset of 
participants between Days 5 and 10.  
Samples will be drawn between days 5 
and 10 at the following timepoints: pre-
dose, 0.5, 1, 1.5, 2, 3, 4, 6,10, and 24 
hours post dose.  See Section 9.6.2.3
Dispense Intensive PK Diary 
Card to Intensive PK sub-set
.
B
.
.
.
.
.
.
.
.
.
.
.
.
.
Participant to complete dosing diary for 
3 days prior to PK sampling visit. The 
PK visit should be re-scheduled if the 
participant took their morning dose 
prior to coming into the clinic on the 
intensive PK sampling day.  

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Procedure
Screeninga
Treatment Phase (Week)
Extension 
Phaseb
Continuation 
Phasec
End Continuation 
Phase Visit
Withdrawal d
Follow Up e
Notes
Baseline/ Day 1
1
4
8
12
16
24
36
48
Every 12 
weeks 
after 
Week 48 
through 
Week 144
Every 12 
weeks after 
Week 144
.
.
.
Whole blood sample (virology)
.
B
.
.
.
.
.
.
.
48
E
(at Week 
144)
.
.
W
F
Whole blood (Virology) may be used 
for virologic analyses as described in 
the protocol. In the Extension Phase, 
collect only at Week 144.
Study Treatment
IVRS/IWRS
SC
B
1
4
8
12
16
24
36
48
E
C
EC
W
F
Dispense study medication
.
B
.
4
8
12
16
24
36
48
E
C
.
.
.
Medication may be dispensed until the 
participant’s last on study visit.
Study medication accountability 
.
.
.
4
8
12
16
24
36
48
E
C
EC
W
.
anti-HBc = antibody to hepatitis B core antigen, anti-HBs = hepatitis B surface antibody, ART = antiretroviral therapy, B= Baseline, C= Continuation Phase, CDC = Centers for Disease 
Control and Prevention, DNA = deoxyribonucleic acid, E = Extension Phase Visit, EC= End of Continuation Phase Visit, ECG = electrocardiograph, F= Follow-up Visit, HBsAg = hepatitis B 
surface antigen, HCV = hepatitis C virus, HIV-1 = human immunodeficiency virus type 1, INR = international normalized ratio, IVRS = interactive voice recognition system, IWRS = interactive 
web recognition system, PMTCT = prevention of mother to child transmission, RNA = ribonucleic acid, RPR = rapid plasma regain, SC= Screening, W= Withdrawal Visit

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3.
INTRODUCTION
3.1.
Study Rationale
Current HIV treatment guidelines recommend first-line antiretroviral (ARV) regimens 
consisting of two nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) 
as a “backbone” combined with a third agent from the non-nucleoside reverse 
transcriptase inhibitor (NNRTI), protease inhibitor (ritonavir-boosted) (PI/RTV), or 
integrase strand transfer inhibitor (INSTI) classes [DHHS, 2019; EACS, 2020; 
International Antiviral Society -USA, 2018].  These regimens are highly efficacious and 
generally well tolerated.  However, because these regimens need to be taken life-long, 
there is growing concern about long-term toxicities thus there is great interest from 
patients and clinicians in unique regimens that might avoid such toxicities by minimizing 
the number of antiretrovirals without sacrificing long-term antiviral efficacy.
DTG is a potent dual cation binding INSTI, exhibiting rapid reduction in viral load, best 
in class efficacy, and a high barrier to resistance.  In addition, due to its mechanism of 
metabolism, DTG lacks many of the frequent drug interactions associated with other 
medications commonly taken by HIV-positive patients.  To date, the efficacy, 
pharmacokinetics (PK), safety and drug interaction potential of DTG has been evaluated 
in an extensive program of Phase I to IIIB clinical trials [TIVICAY Package Insert, 2020; 
DTG Investigators Brochure GlaxoSmithKline Document Number RM2007/00683/12].
3TC is a potent cytidine nucleoside analogue without major side effects and has a well 
proven safety profile.  Available since 1995 as a single agent [EPIVIR™ Package Insert, 
2020], it is also available as part of the FDC products COMBIVIR (zidovudine 
(ZDV)/3TC), TRIZIVIR (abacavir (ABC)/ZDV/3TC), EPZICOM/KIVEXA (ABC/3TC) 
and TRIUMEQ (DTG/ABC/3TC).  3TC monotherapy is known to select for resistance 
due to a single point mutation that reduces antiviral activity.  However, it is predicted that 
3TC, when combined with DTG with its high barrier to resistance and ability to confer a 
very rapid decline in HIV-1 RNA, may be less likely to select for resistance consistent 
with clinical studies combining DTG, 3TC and ABC [DTG Investigators Brochure 
GlaxoSmithKline Document Number RM2007/00683/12; Walmsley, 2013].
DTG plus 3TC FDC (50/300 mg) is marketed as DOVATO and approved in the United 
States, Canada, Europe and multiple other markets. DTG plus 3TC provides a novel, 
well-tolerated two-drug first-line regimen for HIV-infected treatment- naïve patients, 
limiting the risk of many common adverse reactions associated with other ARV drugs.  
This regimen is particularly valuable for patients with co-morbid conditions such as bone 
or cardiovascular disease, and in resource-limited settings due to DTG’s known efficacy 
advantages and both drugs’ tolerability and long-term safety profiles, as well as ease of 
use (once daily dosing, no food dosing effects/requirements, and limited potential for 
drug-drug interactions).
The combination of DTG plus 3TC is under investigation in 2 large, randomized, double-
blind, active controlled clinical trials in adult participants (GEMINI-1 and GEMINI-2 
Studies 204861 and 205543).  GEMINI 1 and GEMINI 2 showed that in adult HIV-1 
infected ART-naïve participants with a Screening HIV-1 RNA of ≥500,000 copies/mL 

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(c/mL) and with no drug-resistance mutations, DTG + 3TC was non-inferior to DTG + 
tenofovir disoproxil fumarate/ emtricitabine  (TDF/FTC) at Week 48 [Cahn, 2019]. The 
proportion of participants with plasma HIV-1 RNA <50 c/mL was similar in each 
treatment group. At least 90% of participants in each treatment group had plasma HIV-1 
RNA <50 c/mL using the Snapshot algorithm. DTG + 3TC was effective across a diverse 
spectrum of ART-naïve participants, including those with high Baseline HIV-1 RNA 
(>100,000 c/mL). DTG plus 3TC continued to offer non-inferior efficacy to DTG plus 
TDF/FTC at Week 96 [Cahn, 2019]. A pooled analysis of the two studies at Week 96 
showed that 86% (616/716) in the DTG + 3TC arm had HIV-1 RNA <50 copies per 
millilitre (c/mL) compared with 90% (642/717) in the DTG plus TDF/FTC arm [adjusted 
difference -3.4 (-6.7,0.0)] [Cahn, 2019].  Across both studies, 11 participants (1.5%) on 
DTG plus 3TC and seven (1.0%) on DTG plus TDF/FTC met protocol-defined virologic 
withdrawal criteria through to Week 96. No patient who experienced confirmed virologic 
withdrawal in either treatment arm developed treatment-emergent resistance. The safety 
results for DTG plus 3TC were consistent with the product labelling for the medicines.  
No patient who experienced virologic failure in either treatment arm developed 
treatment-emergent resistance.
Data from this adolescent trial is intended to supplement the dataset in adults.  As such, 
this trial will provide ‘bridging’ information for regulatory authorities and treating 
clinicians (CDER, 2015). The dual combination of DTG plus 3TC will be assessed in 
pediatric participants 2 to <12 years of age in a separate study.
3.2.
Background
A number of clinical studies have reported supportive clinical data on the efficacy as well 
as favorable safety of two-drug treatment regimens as either initial therapy or as switch 
therapy in virologically suppressed patients, when they include a highly-effective ARV, 
such as a boosted PI or an INSTI.
One of the potential risks of a two-drug regimen, such as DTG plus 3TC, is the increase 
in virologic failure associated with the emergence of resistance.  DTG, with its higher 
barrier to resistance, may reduce treatment-emergent resistance in patients taking a two-
drug regimen.  The overall efficacy data from the pivotal Phase III studies of DTG in 
ART-naïve participants are extensive, with no resistance mutations being identified 
through 144 weeks of treatment (SINGLE, ING114467) [Walmsley, 2015].  The absence 
of treatment-emergent mutations to DTG or background agents in ART-naïve 
individuals, rapid virologic response demonstrated for DTG-based regimens, and the in 
vitro potency and well-tolerated safety profile of both DTG and 3TC all provide a strong 
rationale for the development of a DTG/3TC single tablet regimen (STR) as a treatment 
option for patients.  In the Gemini studies, there was no emergent INSTI or NRTI 
resistance observed for participants meeting confirmed virologic withdrawal criterion in 
either the DTG + 3TC or DTG + TDF/FTC treatment arms [Cahn, 2019].

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Two-drug regimens in HIV-1 infected, antiretroviral treatment-naïve 
patients.
Three randomized clinical trials have shown comparable results of PI/RTV-based dual 
therapies among treatment-naïve patients:

The AIDS Clinical Trials Group Study A5142 found that the virological efficacy of an 
NRTI-sparing regimen of efavirenz (EFV) plus lopinavir/ritonavir (LPV/RTV) was 
similar to that of the EFV plus two NRTIs but was more likely to be associated with 
drug resistance [Riddler, 2008].

In the PROGRESS study, patients were randomly assigned to an NRTI-sparing 
regimen of LPV/RTV plus raltegravir (RAL) or a standard triple-therapy regimen
consisting of LPV/RTV plus TDF/FTC FDC [Reynes, 2011].  At 48 weeks, 83.2% of 
participants in the LPV/RTV plus RAL group and 84.6% of those in the LPV/RTV
plus TDF/FTC group achieved plasma viral loads of <50 c/mL, although this study did 
not enroll patients with advanced HIV disease.  The mean baseline HIV-1 RNA was 
low (~18,000 c/mL).

The GARDEL (Global AntiRetroviral Design Encompassing Lopinavir/r and 
Lamivudine vs LPV/r based standard therapy) study randomly assigned 426 treatment-
naïve patients with HIV to receive open-label LPV/RTV (400 mg/100 mg) twice daily 
plus two NRTIs (triple therapy) or an experimental dual therapy regimen of LPV/RTV 
plus 3TC (150 mg) twice daily [Butler, 2017].

[Cahn, 2014].  After 48 weeks of treatment, the virological response rates were 88.3% 
in the dual-therapy group and 83.7% in the triple-therapy group, meeting the study’s 
primary non-inferiority endpoint.  All enrolled participants who maintained viral 
suppression at Week 48 were invited to participate in an extension phase up to Week 
96; non-inferiority was again demonstrated with response rates at Week 96 of 90.3% 
(dual therapy) and 84.4% (triple-therapy) [Cahn, 2015].
In addition, two pilot studies supported the concept of a DTG + 3TC two-drug initial 
regimen.

The PADDLE trial assessed DTG (50 mg once daily) + 3TC (300 mg once daily) as 
initial therapy in 20 HIV treatment-naïve participants with no genotypic resistance to 
3TC and a viral load of ≤100,000 c/mL at Screening.  Participants were enrolled in 
two separate groups of 10, allowing close evaluation of response while employing a 
set of stopping rules with intensive follow-up in each cohort.  At Week 96, all 18 of 
the 20 participants who completed the study had undetectable plasma HIV-1 RNA 
(<50 c/mL).  Two participants discontinued treatment early; 1 due to virologic failure 
at Week 48 and 1 due to a SAE (also at Week 48) [Figueroa, 2017].

ACTG5353 [Taiwo, 2017] enrolled 120 study participants into the pilot study 
assessing DTG (50 mg once daily) + 3TC (300 mg once daily) as initial therapy.  
Participants in this trial had no history or major NRTI, INSTI, nor PI mutations 
(INSTI resistance testing was performed at Screening) and had plasma HIV-1 RNA 
between 1000 and 500,000 c/mL.  At Week 24, 90% of participants had plasma HIV-1 
RNA <50 c/mL.  Three participants had plasma HIV-1 RNA ≥50 c/mL.  Four 
participants discontinued study prior to Week 24 (2 moved location, 1 was 

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incarcerated, 1 was lost to follow up) and three participants discontinued treatment (1 
due to pregnancy, 1 for non-compliance and 1 was unable to attend clinic).
Immunologic responses in both of these trials were positive with increases in CD4+ cell 
counts.
Finally, data from the DOLUAM study [Reynes, 2017] supported the concept of DTG + 
3TC as a switch regimen in maintain virologic suppression in participants with plasma 
HIV-1 RNA <50 c/mL for at least 12 months.  In 27 heavily experiences subjects with 
tolerability issues, there we no reported cases of virologic failure.  Two subjects 
discontinued study early due to AE and one subjects experience a viral ‘blip’ and wanted 
to intensify the antiretroviral regimen.
3.3.
Benefit/Risk Assessment
Summaries of findings from both clinical and non-clinical studies conducted with DTG 
and 3TC can be found in the most recent version of the DTG Investigator’s Brochure (IB) 
and any IB supplements and DTG, 3TC and DOVATO product labels.  The following 
section outlines the risk assessment and mitigation strategy primarily for DTG in this 
protocol.

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3.3.1.
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) [DTG/3TC]
Refer to DTG IB and country product labels for lamivudine for additional information
DTG: Hypersensitivity reaction (HSR) 
and rash
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. 
Participants with history of allergy/sensitivity to any of the study drugs 
are excluded (Section 6.2).
Specific/detailed toxicity management guidance is provided for HSR 
(Section 12.9.1.4) and rash (Section 12.9.1.5).
The participant informed consent form includes information on this risk 
and the actions participants should take in the event of 1) an HSR or 
associated signs and symptoms, or 2) developing any type of rash or 
skin abnormality.  For Grade 3/4 rash, except where the aetiology is 
clear and not associated with study drug or where there is a definitive 
diagnosis clearly attributable to a concomitant medication (and not to 
study drug) or to a concomitant infection, participants must 
permanently discontinue study drug and be withdrawn from the study.
DTG: Drug induced liver injury (DILI) 
and other clinically significant liver 
chemistry elevations
3TC: Use in HBV co-infected 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 participants 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 
participants, likely contributed to significant elevations in liver 
chemistries. A review of postmarketing data found that the 
number of cases reporting particularly severe liver dysfunction 
was found to be very low in the context of exposure to DTG and 
DTG/ABC/3TC. The reported cases of severe liver dysfunction 
(including acute hepatic failure) are complex with potential 
confounding factors but in a very small number of cases, drug-
Participants meeting either of the following criteria during the screening 
period are excluded from participating (Section 6.2).

Alanine aminotransferase (ALT) 5 times the upper limit of normal 
(ULN) or ALT 3x ULN and bilirubin 1.5x ULN (with >35% direct 
bilirubin);

Participants positive for Hepatitis B surface antigen (HBsAg); 
participants negative for HBsAg and negative for Hepatitis B 
surface antibody (anti-HBs or HBsAb) but positive for Hepatitis B 
core antibody (anti-HBc) and positive for HBV DNA;

Participants with an anticipated need for any HCV therapy during 
the first 48 weeks of the study and for HCV therapy based on 
interferon or any drugs that have a potential for adverse drug:drug 
interactions with study treatment throughout the entire study 
period.

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
induced liver injury is likely and the role of DTG containing 
regimens cannot be ruled out particularly in those involving DTG 
with ABC/3TC or DTG/ABC/3TC.
3TC: Current treatment guidelines [DHHS, 2019; EACS, 2020]
do not recommend monotherapy with 3TC for patients with HBV 
infection, which is what participants enrolled 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 participants can result in severe exacerbations of 
hepatitis B.
Specific/detailed liver stopping criteria and toxicity management 
guidance is provided for suspected DILI or other clinically significant 
liver chemistry elevations (Section 12.3 and Section 12.9.1.1).
DTG: Psychiatric disorders
Psychiatric disorders including suicidal ideation and behaviors 
are common in HIV-infected patients. Events of suicidal ideation, 
attempt, behavior and completion were observed in clinical 
studies of DTG, primarily in participants with a pre-existing 
history of depression or other psychiatric illness. The events 
respond rapidly to withdrawal of DTG, or appropriate drug 
therapy and psychiatric support. 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 plus ABC/3TC compared to EFV/TDF/FTC in 
ING114467; however, this was not duplicated in any other 
Phase IIb/III study conducted with DTG.
Participants who in the investigator’s judgment, pose a significant 
suicidality risk, are excluded from participating (Section 6.2).
Because of the elevated risk in the HIV- infected population, treatment 
emergent assessment of suicidality will be monitored during this study.  
Investigators are advised to consider mental health consultation or 
referral for participants who experience signs of suicidal ideation or 
behaviour (Section 9.3.4).
The participant informed consent form includes information on this risk 
of depression and suicidal ideation and behaviours.
DTG and 3TC: Increased rates of 
virologic failure/ observed resistance
Lower responses in participants with higher baseline viral loads 
have been observed in previous treatment-naïve studies, 
including studies with 2-drug arms such as the MODERN study 
[Stellbrink, 2014].
Participants with evidence of primary viral resistance based on the 
presence of any major resistance-associated mutation (including 
M184V) are excluded from this study (Section 6.2). 

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
DTG, with its higher barrier to resistance, may reduce treatment-
emergent resistance in patients taking a two-drug regimen.  
Week 96 and Week 144 analyses for the Phase III/IIIb clinical 
studies demonstrate robust maintenance of viral suppression 
with no finding of HIV-1 resistance in treatment-naïve 
participants.
3TC: M184V is a common single mutation that leads to full 
resistance to 3TC.
The study initially will enroll participants with a Screening HIV 1 RNA of 
1000 to 500,000 c/mL.
Participants will have HIV-1 RNA measured at each study visit. An 
Independent data monitoring committee (IDMC) will be instituted to 
ensure external objective medical and/or statistical review of efficacy 
and safety (Section 12.4.5).  An ad-hoc review of data by the IDMC will 
be triggered whenever the number of CVWs exceeds thresholds pre-
specified in the IDMC charter (Section 12.4.5).
DTG: Theoretical serious drug 
interaction with dofetilide, pilsicainide 
and fampridine (also known as 
dalfampridine)
Co-administration of DTG may increase 
dofetilide/pilsicainide/fampridine plasma concentration via 
inhibition of organic cation transporter 2 (OCT2), resulting in 
potentially life-threatening toxicity. 
The co-administration of DTG with dofetilide, pilsicainide or fampridine 
is prohibited in the study (Section 7.9.2).
DTG, 3TC: Renal function
Mild elevations of creatinine have been observed with DTG 
which are related to a likely benign effect on creatinine secretion 
with blockade of OCT2.  DTG has been shown to have no 
significant effect on glomerular filtration rate (GFR) or effective 
renal plasma flow.
3TC, is eliminated by renal excretion and exposures increase in 
patients with renal dysfunction
Participants with a creatinine clearance (CrCL) <50 mL/min/1.73 m2
are excluded (Section 6.2).
CrCl is calculated in all patients prior to initiating therapy, and renal 
function (CrCl, serum electrolytes) will continue to be monitored at all 
subsequent study visits. Other measures of renal function, such as 
urine protein and urine creatinine, will be measured at regular, less 
frequent intervals throughout. 
Specific/detailed toxicity management guidance is provided for 
participants who develop a decline in renal function (Section 12.9.1.3).
DTG: Rhabdomyolysis and Creatine 
Phosphokinase (CPK) elevations
Grade 3 to 4 CPK elevations have been observed with DTG. 
Creatine phosphokinase (CPK) elevations were mainly in 
association with exercise and asymptomatic.
No increased risk for clinically significant or serious 
musculoskeletal disorders such as rhabdomyolysis have been 
Specific detailed toxicity management guidance is provided for 
participants who develop Grade 3 to 4 CPK elevations (Section
12.9.1.7).

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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
identified for DTG with longer exposure. However, as  
rhabdomyolysis and myositis are labelled for RAL this is 
therefore considered a potential risk for DTG.
DTG:  Neural tube defects 
3TC:
In a birth outcome surveillance study in Botswana, a numerically 
higher rate of neural
tube defects was reported with exposure to DTG compared to 
non-dolutegravir containing antiretroviral regimens at the time of 
conception, however, the difference was not statistically 
significant. Seven cases of neural tube defects were reported in 
3,591 deliveries (0.19%) to mothers taking DTG-containing 
regimens at the time of conception, compared with 21 cases in 
19,361 deliveries (0.11%) to mothers taking non-DTG containing
regimens at the time of conception (Prevalence Difference 
0.09%; 95% CI -0.03-0.30).
In the same study, no increased risk of neural tube defects was 
reported in women who started DTG during pregnancy. Two out 
of 4,448 deliveries (0.04%) to mothers who started DTG during 
pregnancy had a neural tube defect, compared with 5 out of 
6,748 deliveries (0.07%) to mothers who started non-DTG-
containing regimens during pregnancy.
Available data from the Antiretroviral Pregnancy Registry show 
no difference in the risk of overall major birth defects for 
lamivudine compared with the background rate for major birth 
defects of 2.7% in the US reference population of the 
Metropolitan Atlanta Congenital Defects Program (MACDP). 
Lamivudine produced embryonic toxicity in rabbits at a dose that 
produced similar human exposures as the recommended clinical 
dose. The relevance of animal findings to human pregnancy 
registry data is not known.
Females of childbearing potential are required to have a negative 
pregnancy test at both Screening and Day 1 of the study.
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 10, Section 12.10.1) 
from 28 days prior to the first dose of study medication and until 
the last dose of study medication and completion of the Follow-up 
visit.
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 will have study treatment discontinued and 
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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3.3.2.
Benefit Assessment
DTG is conveniently dosed once daily, without need for a PK booster, and with limited 
safety implications resulting from theoretical or actual drug:drug interactions compared 
to other ARV agents.  DTG and 3TC in combination with other ARVs has demonstrated 
durable virologic and immunologic response.  In addition, the high barrier to resistance 
observed with DTG should help protect against the development of resistance to both 
components of the DTG plus 3TC regimen.
Two-drug regimens have been tested in a number of clinical trials (see Section 3.2).  
Results from these trials paved the way for the exploration of other dual-therapy 
strategies.  DTG plus 3TC, a regimen of two well-characterized antiretrovirals, provides a 
novel, well-tolerated two-drug regimen for HIV-infected patients, limiting the risk of 
many common adverse reactions associated with other ARV drugs.  Dual therapy also 
has the potential benefit of decreasing the likelihood of drug-drug interactions and 
preserving future treatment options by limiting drug exposure.
Study participants may also benefit from the medical tests and screening procedures 
performed as part of the study.
3.3.3.
Overall Benefit:Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in 
this study, the potential risks identified in association with DTG/3TC are justified by the 
anticipated benefits that may be afforded to HIV-1 infected treatment-naïve adolescents 
starting this two-drug first-line regimen.
4.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To assess the antiviral activity of 
DTG/3TC in antiretroviral naïve HIV-1 
infected adolescents.

The proportion of participants with plasma 
HIV-1 RNA less than 50 c/mL at Week 48 
using the Snapshot algorithm (ITT-E 
population).
Secondary

To assess the early antiviral activity of 
DTG/3TC and to determine the extended 
long term (≥48 weeks) safety, tolerability, 
and viral response of DTG/3TC in 
antiretroviral naïve HIV-1 infected 
adolescents.

Proportion of participants with plasma HIV-
1 RNA <200 and <50 copies/mL at Week 
24, Week 96 and Week 144.

Proportion of participants with plasma HIV-
1 RNA <200 copies/mL at Week 48

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Objectives
Endpoints

Incidence and severity of AEs and 
laboratory abnormalities through 144 
weeks

Proportion of participants who discontinue 
treatment due to AEs through 144 weeks

Safety and tolerability assessments at 
Weeks 96 and 144.

Viral load monitoring after Week 48 
through Week 144.

To evaluate the effect of DTG/3TC on 
immunologic response from baseline to 24 
and 48 weeks.

Change from baseline in CD4+ and CD8+ 
cell count and ratio at Week 24 and 48.

Incidence of disease progression (HIV-
associated conditions, AIDS, and death) 
through Weeks 24 and 48.

To assess the safety and tolerability of 
DTG/3TC in HIV-1 infected adolescents at 
24 and 48 weeks.

Incidence and severity of AEs and 
laboratory abnormalities through 24 and 
48 weeks.

Proportion of participants who discontinue 
treatment due to AEs through 24 and 48 
weeks.

To assess DTG and 3TC exposure and to 
evaluate the steady-state 
pharmacokinetics of DTG and 3TC in HIV-
1 infected adolescents.

Steady-state plasma PK parameters of 
DTG and 3TC will be assessed using 
intensive PK collected in a subset of 
participants

To assess development of viral resistance 
to DTG and 3TC in participants 
experiencing protocol-defined virologic 
failure (i.e. meeting confirmed virologic 
withdrawal criteria).

Incidence of observed genotypic and 
phenotypic resistance to DTG and 3TC for 
participants meeting confirmed virologic 
withdrawal criteria. 
All virologic endpoints will be determined in a central laboratory.
5.
STUDY DESIGN
5.1.
Overall Design
This is a Phase IIIb, single-arm, open-label, multi-center assessment of DTG/3TC in 
approximately 30 HIV-1 infected, treatment-naive adolescents with plasma HIV-1 RNA 
between 1,000 and ≤500,000 c/mL.  All enrolled participants will receive an open-label, 
two-drug regimen of DTG/3TC for 48 weeks.  Participants who successfully complete 48 
weeks of treatment may enter the study Extension Phase for an additional 96 weeks.  At 

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the end of the study, participants who continue to receive benefit from DTG/3TC and for 
whom these medications are not locally accessible, will have access to medication in a 
Continuation Phase until it is available locally (See Section 7.10).
Data from this study will be used to assess the safety, efficacy and tolerability of this 
combination of DTG/3TC in adolescents relative to what is observed in large and 
controlled clinical studies being conducted in adults.
The study will comprise:

Screening Phase (approximately Day -28 to Day 1)

Treatment Phase (Day 1 to Week 48)

Extension Phase (Week 48 to Week 144)

Continuation Phase (After Week 144; See Section 7.10)
Figure 1
205861 Study Schematic
5.2.
Number of Participants
Approximately 80 participants will be screened to achieve 30 enrolled participants.  See 
Section 10.1 for sample size determination details.
Participants who prematurely discontinue the study will not be replaced.
A subset of approximately 12 participants will provide intensive PK samples to ensure 
data are available from at least 10 evaluable participants.

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5.3.
Participant and Study Completion
A participant will be considered evaluable for the primary endpoint if he/she is 
successfully treated exclusively with DTG/3TC and has completed 48 weeks of treatment 
or is classified as a treatment failure (met any withdrawal criteria).
A participant will be considered to have completed treatment if he/she completes the 
Week 48 study visit while still taking DTG/3TC.
A participant will be considered to have completed the study if he/she completes 48 
weeks of treatment and either completes the follow up visit or continues into the 
Extension Phase of this study.
A participant will be considered to have completed the Extension Phase if he/she 
completes the Week 144 visit.
A participant will be considered to have completed the Continuation Phase after 
completion of the End of Continuation Phase Visit.
The end of the study will occur after the last participant visit occurs.
The end of the study is defined as the date of the last visit of the last participant in the 
study.
5.4.
Scientific Rationale for Study Design
This study is being conducted to fulfill regulatory requirements and is intended to further 
inform on the safety and effectiveness and PK of DTG/3TC FDC in adolescent 
participants and is intended to supplement the adequate and well-controlled data set being 
generated in adult participants, an open-label trial is appropriate.  This study is not
powered to test an efficacy hypothesis and is intended to generate safety and descriptive 
efficacy data; therefore a comparator is not relevant.
5.5.
Dose Justification
The efficacy, PK, safety, and drug interaction potential of DTG and 3TC as individual 
agents have been evaluated in extensive clinical development programs.  DTG and 3TC 
are approved and marketed as TIVICAY 50 mg once daily and EPIVIR 300 mg once 
daily, respectively. In addition, the fixed dose combination of DTG plus 3TC is approved 
in the United States, Canada and EU and is marketed as DOVATO. 
The use of DTG plus 3TC (50 mg/300 mg) is supported by the approved 3TC 300 mg 
total daily dose for children weighing ≥25 kg , which may be taken as 150 mg BID or 
300 mg once daily [EPIVIR™ Package Insert, 2020]; and DTG PK data from the 
paediatric ODYSSEY study. The ODYSSEY study is an open-label, randomized, non-
inferiority, Phase II/III, trial comparing the efficacy and safety of DTG-based ART 
versus standard of care in children aged less than 18 years who are starting first-line ART 
or switching to second-line ART. A crossover PK substudy within ODYSSEY provided 
within-patient comparative PK and safety data in children weighing 25 kg to ≤40 kg, 

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switching from 25 mg and 35 mg DTG film coated tablet (FCT) doses to the adult 50 mg 
FCT dose, in order to simplify DTG administration. Data from this substudy indicate that 
in children weighing 25 kg to less than 40 kg, DTG 50 mg achieve appropriate plasma 
exposure as Ctrough and AUC0-24 h were comparable to DTG exposures in adults on 
50 mg daily. For children weighing 25 kg to less than 30 kg, after switching from DTG 
25 mg to DTG 50 mg, Ctrough and AUC0-24h values were 0.75(42) mg/L and 58.7(27) 
h*mg/L respectively. For children weighing 30 kg to less than 40 kg, after switching 
from DTG 35mg to DTG 50 mg, Ctrough and AUC0-24h values were 0.63(49) mg/L and 
53.5(32) h*mg/L respectively. For adults, DTG 50 mg Ctrough and AUC0-24 h reference 
values (VIKING study, 112961) were 0.83(26) mg/L and 43.4(20) h*mg/L respectively. 
[Turkova, 2018].  
6.
STUDY POPULATION
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 participants for a trial of an oral medication, taking into consideration 
any local treatment practices or guidelines and good clinical practice (GCP).
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on DTG/3TC that may impact participant eligibility is 
provided in the DTG IB and the product labels for TIVICAY, EPIVIR and DOVATO. To 
assess any potential impact on participant eligibility with regard to safety, the investigator 
must refer to the IB and supplements, approved product labels, and/or local prescribing 
information for detailed information regarding warnings, precautions, contraindications, 
AEs, drug interactions, and other significant data pertaining to the study drugs.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.  Deviations from inclusion 
and exclusion criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability or participant safety.  Therefore, 
adherence to the criteria as specified in the protocol is essential.
Participants are allowed to re-screen for this study one time, except where exclusionary 
HIV-1 resistance was present; re-screening will require a new participant screening 
number.
With the exception of a disqualifying viral genotype, a single repeat test (re-test) per 
analyte or assessment is allowed during the screening period to determine eligibility.  
Laboratory results provided from the central laboratory services will be used to assess 
eligibility.
The screening period for this study is defined as 28 days prior to the first dose of study 
medication.  In cases of central laboratory assay failure or shipment failure, the screening 
period may be extended to 35 days to accommodate sample analysis and reporting.  
Approval of the Medical Monitor is required.
The study team will monitor gender distribution during the recruitment period to ensure 
adequate numbers of females and males are included in this study.

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6.1.
Inclusion Criteria
Eligible participants 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 oral medication (e.g. consideration of substance abuse, no acute major organ 
disease, no significant gastrointestinal disturbance that would interfere with absorption, 
etc.).
It is the responsibility of each investigator to carefully assess participants for suitability 
for participation in a clinical trial of an investigational agent.  This includes assessment of 
physical and mental conditions, including substance abuse, which could significantly 
impact ability to complete protocol visits and assessments.  Additionally, investigators 
must understand and be prepared to manage potential barriers to appropriate compliance 
with trial assessments.
A participant will be eligible for inclusion in this study only if all of the following criteria 
apply: 
AGE AND WEIGHT
1. HIV-1 infected adolescents 12 to <18 years of age at the time of signing the 
informed consent form.
2. Weight 25 kg at the time of signing the informed consent form.
TYPE OF PARTICIPANT AND DIAGNOSIS INCLUDING DISEASE 
SEVERITY 
3. Screening plasma HIV-1 RNA between 1,000 and 500,000 c/mL.
4. Antiretroviral-naïve (defined as no prior therapy with any antiretroviral agent for 
the treatment of HIV following a diagnosis of HIV-1 infection). 
-
Participants who received antiretroviral therapy for prevention of mother to 
child transmission of HIV in the first 3 months of life are allowed.
-
Participants who received HIV post-exposure prophylaxis (PEP) or pre-
exposure prophylaxis (PrEP) in the past are allowed as long as the last 
PEP/PrEP dose was >6 months from HIV diagnosis or there is documented 
HIV seronegativity at least 2 months after the last prophylactic dose and 
prior to the date of HIV diagnosis. The study site must have documentation 
of the seronegative test available and placed into the study source 
documents.

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SEX
5. Male or female.
A female participant is eligible to participate if she is not pregnant (as confirmed by 
a negative serum human chorionic gonadotrophin (hCG) test at Screening and 
negative urine hCG test before Enrollment) and not lactating.
Female participants who are of child bearing potential and who are engaging in 
sexual activity that could lead to pregnancy, must agree to use one of the birth 
control methods listed in Appendix 10 (Section 12.10) from 28 days prior to the first 
dose of study medication, and until 4 weeks after the last dose of study medication 
(and completion of the Follow-up visit). Condoms are recommended in addition, 
because their appropriate use is the only contraception method effective for 
preventing HIV-1 transmission.
The investigator is responsible for ensuring that participants understand how to 
properly use these methods of contraception.
All participants participating in the study should also be counselled 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
6. The participant’s parent(s) or legal guardian or the participant is capable of giving 
signed informed consent as described in Section 12.4.3 which includes compliance 
with the requirements and restrictions listed in the consent form and in this 
protocol.  Where applicable, participants must provide written assent.
6.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY
1. Females 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 and/or Category C or WHO Stage 4 disease (Appendix 6, Section 12.6), except 
cutaneous Kaposi’s sarcoma not requiring systemic therapy and historical or 
current CD4 cell counts less than 200 cells/mm3 or CD4% <15%.
3. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh 
classification (Section 12.2).
4. Unstable liver disease (as defined by the presence of ascites, encephalopathy, 
coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent 

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jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's 
syndrome or asymptomatic gallstones).
5. Evidence of HBV infection based on the results of testing at Screening for HBV 
surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody 
(anti-HBs or HBsAb), and HBV DNA as follows:

Participants positive for HBsAg are excluded;

Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg 
status) and positive for HBV DNA are excluded.  
NOTE: Participants positive for anti-HBc (negative HBsAg status) and positive 
for anti-HBs (past and/or current evidence) are immune to HBV and are not 
excluded (See Section 12.11, Appendix 11: Decision Flow- Screening Tests for 
Hepatitis B Virus Serology, Interpretation and Action). 
6. Anticipated need for any HCV therapy during the first 48 weeks of the study and 
for HCV therapy based on interferon or any drugs that have a potential for adverse 
drug:drug interactions with study treatment throughout the entire study period.
7. Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening 
without clear documentation of treatment).  Participants who are at least 24 hours 
post completed treatment are eligible.
8. History or sensitivity to any of the study medications or their components or drugs 
of their class, or a history of drug or other allergy that in the opinion of the 
Investigator or Medical Monitor contraindicates participation.
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; other localized malignancies require agreement 
between the investigator and the Study Medical Monitor for inclusion of the 
participant.
10. Participants who in the investigator’s judgment, poses a significant suicidality risk.  
Recent history of suicidal behavior and/or suicidal ideation may be considered as 
evidence of serious suicide 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
i.
radiation therapy,
ii.
cytotoxic chemotherapeutic agents,

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iii.
any systemic immune suppressant;
13. Treatment with any agent with documented activity against HIV-1 in vitro within 
28 days of first dose of study treatment.
14. Receipt of any prohibited mediation listed in Section 7.9.2 and inability or 
unwillingness to switch to an alternative medication.
15. 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 treatment.
LABORATORY VALUES OR CLINICAL ASSESSMENTS AT SCREENING
16. Any evidence of pre-existing viral resistance based on the presence of any major 
resistance-associated mutation [International Antiviral Society -USA, 2017] in the 
Screening result or, if known, in any historical resistance test result.  NOTE: retests 
of disqualifying Screening genotypes are not allowed.
17. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during 
the Screening period to verify a result.
18. Any acute laboratory abnormality at Screening, which, in the opinion of the 
Investigator, would preclude the participant’s participation in the study of an 
investigational compound.
19. Alanine aminotransferase (ALT) 5 times the upper limit of normal (ULN) or ALT 
3xULN and bilirubin 1.5xULN (with >35% direct bilirubin).
20. Creatinine clearance of <50 mL/min/1.73 m2 using the Schwartz equation method.
OTHER CRITERIA
21. Children who are wards of the state or government.
6.3.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently enrolled. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse events (SAEs) (see Section 
9.3.1).

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Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened for this study one time within 30 days, except where exclusionary 
HIV-1 resistance was present; re-screening will require new screening number.
Retesting of an exclusionary laboratory result, except for exclusionary HIV-1 resistance, 
is allowed during the screening period and does not require a new screening number.
7.
TREATMENTS
Study treatment is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.  In this trial, study treatment will be the fixed dose combination of 
DTG/3TC.
7.1.
Treatments Administered
Study Treatment
Product name:
DTG + 3TC FDC
Formulation description:
Clinical Trial Material
Dosage form:
Tablet
Unit dose strength(s)/Dosage level(s):
50 mg/300 mg
Route of Administration:
Oral
Dosing instructions:
Take one tablet daily.
7.2.
Dose Modification
Not applicable.
7.3.
Treatment Assignment
Participants will be centrally enrolled using an Interactive Voice/Web Response System 
(IVRS/IWRS).  Before the study is initiated, the telephone number and call-in directions 
for the IVRS and/or the log in information and directions for the IWRS will be provided 
to each site.
Study treatment will be dispensed at the specified study visits summarized in the SoA.
Returned study treatment will not be re-dispensed to participants.
Informed consent must be obtained prior to any study procedures, including any 
screening assessment.  Eligible participants will be provided open-label study treatment.  
Study enrollment will be facilitated by the interactive voice/web recognition system 
(IVRS/IWRS).  Following confirmation of fulfilment of study entry criteria, study site 

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personnel will be required to contact the IVRS/IWRS to enroll participants.  Each 
participant will be assigned a unique identifier and a unique treatment number. 
Participants will maintain the same study treatment through study discontinuation.
Participants who are enrolled into the study and subsequently withdrawn may not be 
rescreened.  Once a participant number has been assigned it must not be re-assigned.
7.4.
Blinding
This is an open-label, single-arm study, therefore blinding will not be used.
7.5.
Packing and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements.
7.6.
Preparation/Handling/Storage/Accountability

The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment.

Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatment 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized site staff.

The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study treatment 
are provided in the Investigator site file.

Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.

A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
ViiV Healthcare/GSK.
7.7.
Compliance with Study Treatment Administration
Compliance with study treatment will be assessed through querying the participant during 
the site visits and documented in the source documents and eCRF.  Study treatment 
accountability will be evaluated using pill counts of unused study treatment (DTG/3TC).  
This assessment will be conducted each time the participant receives a new (refill) supply 
of study treatments through the Withdrawal visit or study completion.  These data will be 
recorded in the participant’s eCRF and may be summarized for analysis purposes.

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Additionally, at each visit, participants will be asked about missed doses and the primary 
reasons or barriers for missing doses. Answers to these queries will be recorded in the 
eCRF and summarized.
7.8.
Study Treatment Overdose
For this study, any tablet intake exceeding the prescribed daily number of tablets for 
study treatment, e.g. more than one tablet, will be considered an overdose (see 
[TIVICAY Package Insert, 2020]; [EPIVIR Package Insert, 2020]).  The Investigator
should use clinical judgment in treating overdose, as ViiV Healthcare/GSK is unable to
recommend specific treatment.
For the purposes of this study, an overdose is not an AE (see Section 9.3.1) unless it is 
accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is an SAE (see Section 9.3.1). 
If an overdose occurs and is associated with an adverse event requiring action, study 
medications should be temporarily discontinued until the adverse event resolves.
7.9.
Concomitant Therapy
Participants should be advised to notify their investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
drug:drug interactions between such treatments and the study drugs.  The investigator 
should evaluate any potential drug:drug interactions at every visit, including reviewing 
the most current version of the U.S. and local prescribing information for DTG and 3TC, 
especially if any new concomitant medications are reported by participants.  All 
concomitant medications taken during the study will be recorded in the eCRF.
If any treatments for Coronavirus Disease-2019 (COVID-19) are planned for a study 
participant, please consult with the Study Medical Monitor to ensure that relevant drug 
interactions are considered and to ensure that continued study participation remains 
appropriate.  Refer to Section 12.12 (Appendix 12 COVID-19 Guidance) for safety 
reporting requirements and instruction for data capture.
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy.
7.9.1.
Permitted Medications and Non-Drug Therapies
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study (except prohibited medications described in 
Section 7.9.2).  Chemoprophylaxis for HIV-associated conditions is encouraged, if 
appropriate, at the discretion of the participant and their physician.  All concomitant 
medications, blood products, and vaccines taken during the study will be recorded in the 
eCRF 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 

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immediately after a scheduled visit after all samples for laboratory tests have been drawn 
and only when scheduled visits are ≥4 weeks apart.  This approach will minimize the risk 
of non-specific 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 or sucralfate containing polyvalent cations (e.g. aluminium and 
magnesium) 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 calcium or iron supplements.
Metformin concentrations may be increased by DTG.  A dose adjustment of metformin 
should be considered when starting and stopping co-administration of DTG/3TC with 
metformin, to maintain glycemic control.
Clinical monitoring is recommended for participants taking methadone as methadone 
maintenance therapy may need to be adjusted in some participants.
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 participant. 
7.9.2.
Prohibited Medications and Non-Drug Therapies
The following concomitant medications or therapies are not permitted at any time during 
the study:

HIV immunotherapeutic vaccines are not permitted at any time during the study (see 
Section 7.9.1 for guidance regarding non-HIV vaccines). 

Other experimental agents, ART drugs not otherwise specified in the protocol, 
cytotoxic chemotherapy, or radiation therapy (see Exclusion Criteria, Section 6.2). 

Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the Investigator site file).  
This includes topical agents with substantial systemic exposure and systemic effects.  
Use of topical imiquimod is permitted.

HCV therapy during the study is prohibited during the first 48 weeks; interferon-
based HCV therapy and HCV therapy based any drugs that have a potential for 
adverse drug:drug interactions with study treatment are prohibited throughout the 
entire study. 

Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided; 
however, topical, inhaled or intranasal use of glucocorticosteroids of any duration 
will be allowed.  Short treatment courses (14 days or less) of oral prednisone/ 
prednisolone/methylprednisolone are allowed.

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
For participants with an unanticipated requirement for HCV therapy during study, 
interferon or any other medications that have a potential for adverse drug-drug 
interactions with study treatment are prohibited during the conduct of the study.

Acetaminophen is not to be used in patients with acute viral hepatitis [James, 2009].

The following medications or their equivalents may cause decreased concentrations 
of DTG and therefore must not be administered concurrently with DTG/3TC.

Carbamazepine

Oxcarbamazepine

Phenobarbital

Phenytoin

Rifampicin or rifapentine

St. John’s wort (Hypericum perforatum)
Dofetilide, pilsicainide and fampridine (also known as dalfampridine) are prohibited as 
DTG may inhibit their renal tubular secretion resulting in increased 
dofetilide/pilsicainide/fampridine concentrations and potential for toxicity.
NOTE: Any prohibited medications that substantially decrease DTG 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 and 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.
For information on concurrent therapies and interactions suspected to be relevant to other 
antiretroviral therapy in the regimen, please consult the local prescribing information.
7.10.
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 participant’s medical condition, whether or not ViiV Healthcare is 
providing specific post-study treatment.
Participants who successfully complete 48 weeks of treatment will have the opportunity 
to continue to receive DTG/3TC through Week 144 in the study Extension Phase.
If required by local regulations, study participants who have successfully completed both 
the Treatment Phase through 48 weeks and the Extension Phase through Week 144 will 
be given the opportunity to continue to receive DTG/3TC once daily in the Continuation 
Phase until:

DTG and 3TC are both locally approved for use as part of a dual regimen, and the 
single entities of DTG and 3TC are available to patients (e.g. through public health 
services), or

the DTG/3TC FDC tablet, if required by local regulations, is locally approved and 
available (e.g. commercially or through public health services), or

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
the participant no longer derives clinical benefit, or

the participant meets a protocol-defined reason for discontinuation, or 

development of the DTG plus 3TC dual regimen is terminated.
Participants completing the Continuation Phase must return to the clinic for a final End of 
Continuation Phase Visit when transitioning to locally approved available supply. At this 
final visit, the site will conduct study assessments noted within the End of Continuation 
Phase Visit column of the SOA (See Section 2).
8.
DISCONTINUATION CRITERIA
Participants permanently discontinuing study treatment are considered to be withdrawn 
from the study.  Similarly, participants who enter the Extension Phase and Continuation 
Phase but permanently discontinue participation prior to transitioning to commercially 
available DTG + 3TC are considered to be withdrawn from study treatment and from the 
study.  Withdrawn participants will not be replaced.
8.1.
Discontinuation of Study Treatment
8.1.1.
Virologic Criteria for Withdrawal, Participant Management and 
Viral Resistance Testing
For the purposes of clinical management in this study, suspected virologic withdrawal 
(SVW) and confirmed virologic withdrawal (CVW) criteria are defined here wherein 
the virologic withdrawal criteria revolve around the HIV-1 RNA cut-off of 200 c/mL.
8.1.1.1.
Virologic Withdrawal Criteria
Suspected Virologic Withdrawal criteria

A single HIV-1 RNA value as defined by Virologic Non-response or Virologic 
Rebound (see below)
Confirmed Virologic Withdrawal criteria

A second and consecutive HIV-1 RNA value meeting Virologic Non-response or 
Rebound 
Virologic withdrawal criteria must be confirmed for each criterion by a repeat and 
consecutive plasma HIV-1 RNA measurement between 2 and 4 weeks after the 
participant met a SVW criterion unless a delay is necessary to meet the requirements of 
confirmatory HIV-1 RNA testing as described below in Section 8.1.1.2.  For the purposes 
of clinical management in this study, virologic withdrawal criteria are defined as any of 
the following:
Virologic Non-response

A decrease in plasma HIV-1 RNA of less than 1 log10 c/mL at or after Week 12, with 
subsequent confirmation, unless plasma HIV-1 RNA is <200 c/mL.

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
Confirmed plasma HIV-1 RNA levels ≥200 c/mL at or after Week 24.
Virologic Rebound

Confirmed rebound in plasma HIV-1 RNA levels to ≥200 c/mL after prior confirmed 
suppression to <200 c/mL.
Participants who meet any CVW criterion must be discontinued from the study.
Cases of participants meeting CVW criteria will trigger virologic resistance testing.  
Investigators should use their discretion as to the most appropriate clinical management 
of their participants if more stringent local guidelines apply.
8.1.1.2.
Managing Participants Meeting Suspected Virologic Withdrawal Criteria
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic withdrawal criteria.  Upon notification that a participant’s HIV-1 RNA 
plasma level qualifies him/her as meeting an SVW criterion, the Investigator should 
query the participant regarding intercurrent illness, recent immunisation, or interruption 
of therapy as inadequate adherence is a common cause of elevated HIV-1 RNA 
measurements.
All cases that meet an SVW criterion must be confirmed by a second measurement 
performed at least 2 weeks but not more than 4 weeks apart from the date of the 
original sample, unless a delay is necessary to meet the requirements of 
confirmatory HIV-1 RNA testing as outlined below.
The following guidelines should be followed for scheduling confirmatory HIV-1 RNA 
testing in an effort to avoid false-positive results:

Confirmatory testing should be scheduled 2 to 4 weeks following resolution of any 
intercurrent illness, during which time the participant should receive full doses of all 
study drugs.

Confirmatory testing should be scheduled at least 4 weeks following any 
immunisation, during which time the participant should receive full doses of study 
drugs.

If therapy is interrupted due to toxicity management, non-compliance, or other 
reasons, confirmatory testing should be scheduled 2 to 4 weeks following 
resumption of full doses of study drugs.

The participant should have received full doses of study drugs for at least 2 weeks at 
the time confirmatory plasma HIV-1 RNA is done.
Sites should contact Medical Monitor to discuss individual participants, whenever 
necessary.
8.1.1.3.
Managing Participants Meeting Confirmed Virologic Withdrawal Criteria
Once a participant has been confirmed as meeting a virologic withdrawal criterion, the 
‘plasma for storage’ sample from the time of meeting SVW criteria and the Day 1 sample 

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will be sent as soon as possible for genotypic and phenotypic resistance testing and the 
result made known to the Investigator if and when available.
Note: shipment of storage samples must occur promptly following confirmation of a 
virologic withdrawal criterion and separately from other samples drawn in real 
time at any visit.
Participants may continue to receive study drug at the discretion of the investigator until 
results of resistance testing are available at which time the participant must be withdrawn 
from the study, except in cases where participant samples have HIV-1 RNA <500 c/mL 
as noted below.  A participant who meets a CVW criterion must be discontinued 
from the study.
The protease (PR)/reverse transcriptase (RT)/integrase assays used in this study are not 
validated for plasma HIV-1 RNA levels <500 c/mL.  Nevertheless, for all participants 
who meet CVW Criteria, additional plasma samples will be analysed in an attempt to 
obtain genotype/phenotype data on as many samples as possible. Participants with 
confirmed HIV-1 RNA levels between 200 c/mL and <500 c/mL should be transitioned 
off study drug within 30 days even if no resistance testing data becomes available, as 
genotype/phenotype data may not be reliably generated from plasma samples collected 
from these participants.  
If a participant is prematurely discontinued from participation in the study, the 
Investigator must make every effort to perform the evaluations outlined in the Time and 
Events Schedule (Section 2).  These data will be recorded, as they comprise an essential 
evaluation that needs to be done before discharging any participant from the study.
8.1.2.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf
Discontinuation of study treatment for abnormal liver tests should be considered by the 
investigator when a participant meets one of the conditions outlined below or if the 
investigator believes that it is in the best interest of the participant.

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Liver Chemistry Stopping and Increased Monitoring Algorithm
Liver Chemistry Increased Monitoring Algorithm with Continued Therapy for ALT 
5xULN but <8xULN
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Section 12.3.
8.1.3.
Temporary Discontinuation of Study Treatment
Participants 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, consultation with the Medical Monitor is required.

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8.1.4.
Study Treatment Restart or Rechallenge
If a participant meets liver chemistry stopping criteria do not restart/rechallenge the 
participant with study treatment unless:

ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted,

Ethics and/or Institutional Review Board (IRB) approval is obtained, if required, and

Separate consent for treatment restart/rechallenge is signed by the participant.
Refer to Appendix 5, Section 12.5 for full guidance.
8.2.
Withdrawal from the Study and Stopping Criteria
A participant may withdraw from study treatment at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioural 
or administrative reasons.  If a participant withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records.  Withdrawn participants will not be replaced.
Participants are not obligated to state the reason for withdrawal.  However, the reasons 
for withdrawal, or failure to provide a reason, must be documented by the Investigator on 
the Completion/Withdrawal section of the electronic case report form (eCRF).  Every 
effort should be made by the Investigator to follow up participants who withdraw from 
the study.
Participants 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, consultation with the Medical Monitor is required.
Participants may be prematurely discontinued from the study for any of the 
following reasons:

Participant or Investigator non-compliance ;

At the request of the participant, Investigator, GSK or ViiV Healthcare;

The participant requires concurrent prohibited medications during the course of the 
study. The participant may remain in the study if in the opinion of the Investigator 
and the Medical Monitor such medication will not interfere with the conduct or 
interpretation of the study or compromise the safety of the participant.

The participant becomes a ward of State or any other agency, institution or entity. 
The site Investigator must notify the Study Medical Monitor immediately if a 
participant's guardianship status changes such that they become a ward during the 
study. If this occurs, the ViiV Chief Medical Officer must determine if the 
participant may continue in the study. 

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Participants must be discontinued from the study for any of the following reasons:

Virologic failure criteria as specified in Section 8.1.1.1 are met;

Participant requires substitution or dose modification of DTG or 3TC;

Liver toxicity where stopping criteria specified in Section 8.1.2 are met and no 
compelling alternate cause is identified;

Renal toxicity criteria as specified in Appendix 9 (Section 12.9.1.3) are met and no 
compelling alternate cause is identified;

Grade 4 clinical AE considered causally related to study drug (Appendix 9, Section 
12.9); 

Allergic reaction or rash criteria as specified in Appendix 9 (Section 12.9.1.5) are 
met and no compelling alternate cause is identified;

Pregnancy (intrauterine), regardless of termination status of pregnancy (Section 
9.3.2).  As a reminder, females of reproductive potential who changed 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.

If a participant is prematurely or permanently withdrawn from the study, the 
procedures described in the SoA (Section 2) for the Withdrawal visit – and if 
necessary, the Follow Up visit – are to be performed.
8.3.
Lost to Follow Up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study.

Before a participant is considered lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 

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9.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA.

Protocol waivers or exemptions are not allowed.

Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study treatment.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA.

The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will be described in 
the study informed consent form.

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.
9.1.
Screening and Critical Baseline Assessments
Written and informed consent must be obtained from each potentially eligible 
participant’s legal guardian (or by the participant as required by local law) by study site 
personnel prior to the initiation of any Screening procedures as outlined in this protocol.  
Where appropriate, participants must also provide written assent.  Note: where “informed 
consent” is referred to in this protocol, the term covers both written consent and assent, 
where applicable.  The consent form and assent form must have been approved by the 
IRB/Independent Ethics Committee (IEC).  After providing written informed consent, 
participants will complete Screening assessments to determine participant eligibility.  
Each participant being screened for study enrolment evaluation will be assigned a 
participant screening number at the Screening visit.  This number will be given 
sequentially in chronological order of participant presentation.
9.1.1.
Screening Assessments
Assessment to be conducted as Screening assessments are provided in the SOA Table 
(Section 2).
Eligibility criteria must be carefully assessed at the Screening visit.  Physical 
examinations should be conducted as part of normal routine clinical care but will not be 

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collected systematically in the eCRF.  Vital signs, height, weight and other baseline status 
information will be collected.
Medical and medication history will be assessed as related to the inclusion/exclusion 
criteria listed in Section 6.
Other information to be collected at Screening includes current medical conditions.
The following demographic parameters will be captured: year of birth, sex, race and 
ethnicity.
All participants must provide a plasma sample for determination of viral genotypic 
resistance by the central laboratory.  For eligibility, the resistance report must show no 
evidence of primary viral resistance based on the presence of any major resistance-
associated mutation [International Antiviral Society -USA, 2017].  The study virologists 
will confirm the lack or presence of exclusionary resistance mutations, and communicate 
eligibility based on the resistance test results.
Note: in cases of assay failure at the central laboratory, viral genotypic and phenotypic 
results from a locally available assay may be considered for eligibility.  Prior discussion 
approval with the Medical Monitor will be required.
Severe hepatic impairment is exclusionary and will be assessed by Child-Pugh grading at 
Screening (see Appendix 2, Section 12.2).
CrCl is calculated at Screening, and participants with a CrCL <50 mL/min per 1.73 m2
are excluded due to requirements for dose reduction of 3TC.
Participants with chronic active hepatitis B are excluded.  Evidence of HBV infection is 
based on the results of testing at Screening for HBsAg, anti-HBc, anti-HBs (HBsAb), and 
HBV DNA.  HBV DNA testing will only be performed during screening and prior to 
enrollment for participants with positive anti-HBc and both negative HBsAg and anti-
HBs (past and/or current evidence).
All participants will be screened for syphilis using a rapid plasma reagin (RPR) at 
Screening.  Participants with untreated syphilis infection, defined as a positive RPR 
without clear documentation of treatment, are excluded.  Participants with a positive RPR 
test who have not been treated may be rescreened at least 24 hours after completion of 
antibiotic treatment for syphilis.
Participants who meet all entry criteria may be enrolled as soon as all Screening 
assessments are complete, and the results are available and documented.  All participants 
will complete the Screening period of approximately 28 days prior to Baseline (Day 1) 
during which all clinical and laboratory assessments of eligibility must be performed and 
reviewed.  All Screening results must be available prior to enrollment.
Participants not meeting all inclusion and exclusion criteria at initial screen may be 
rescreened and receive a new participant number one time unless they were excluded for 
reason of having exclusionary historic genotypic resistance.  Participants who are 

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enrolled into the trial and subsequently withdrawn from the study for any reason may not 
be rescreened.
9.1.2.
Baseline Assessments
Assessments to be conducted at Baseline (Day 1) are provided in the SOA Table 
(Section 2).
At Day 1 and prior to enrollment, any changes to the eligibility parameters must be 
assessed and any results required prior to enrollment (e.g. Day 1 urine pregnancy test for 
females) must be available and reviewed.
The electronic Columbia Suicidality Severity Rating Scale (eC-SSRS) must also be 
administered prior to enrollment.
Participants Co-infected with Hepatitis C Virus (HCV)
Investigators should consult current treatment guidelines when considering choice of 
therapy for participants with chronic HCV infection.  Participants with an anticipated 
need for HCV therapy prior to the primary endpoint may not be enrolled into this study.
For participants with an unanticipated requirement for HCV therapy during the conduct 
of the study, the Investigator must consult with the medical monitor.  HCV treatment 
based on interferon or any other medications that have a potential for adverse drug-drug 
interactions with study treatment, is prohibited during the conduct of the study (see 
Section 7.9.2).
9.2.
Efficacy Assessments
Plasma HIV-1 RNA
Plasma for quantitative HIV-1 RNA will be collected according to the SoA Table 
(Section 2).  Methods to be used may include but are not limited to the Abbott RealTime 
HIV-1 Assay with a lower limit of quantitation of 40 c/mL.  In some cases (e.g. where the 
plasma HIV-1 RNA is below the lower limit of detection for a given assay) additional 
exploratory methods may be used to further characterize plasma HIV-1 RNA levels.
Lymphocyte Subsets
Lymphocyte subsets will be collected for assessment by flow cytometry (total 
lymphocyte counts, percentage, and absolute CD4+ cell counts) according to the SOA 
Table (Section 2).

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HIV-1 Classification and HIV Associated Conditions
HIV-associated conditions will be recorded as per the SOA Table (Section 2).  HIV 
associated conditions will be assessed according to the 2014 CDC Classification System 
for HIV Infection in Adults or, where most appropriate, the WHO Clinical Staging 
System of HIV/AIDS for Adults and Adolescents (see Appendix 6, Section 12.6).  
Indicators of clinical disease progression are defined as:
CDC Class A/WHO Stage 1 at enrolment → Stage 3 event;
CDC Class B/WHO Stage 2 at enrolment → Stage 3 event;
CDC Class C/WHO Stage 3 at enrolment → New Stage 3 Event;
CDC Class A, B, C/WHO Stage 1, 2 or 3 at enrolment → Death.
9.3.
Safety Assessments
9.3.1.
Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 8 (Section 12.8).
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 12.8.6). 
9.3.1.1.
Time Period and Frequency for Collecting AE and SAE Information

All SAEs will be collected from the start of treatment until the follow-up visit or 
contact at the time points specified in the SoA (Section 2).  Any SAEs assessed 
as related to study participation (e.g., study treatment, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a ViiV 
Healthcare product will be recorded from the time a participant consents to 
participate in the study.

All AEs will be collected from the start of treatment until the follow-up visit or 
contact at the time points specified in the SoA (Section 2).

Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the case report form (CRF) not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 8 (Section 12.8.6). The investigator will submit any updated SAE data 
to the sponsor within 24 hours of it being available.

Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study treatment or study 
participation, the investigator must promptly notify the Medical Monitor.

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
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 8 (Section 12.8.6).
9.3.1.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.
9.3.1.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 8.3).  Further information on follow-up procedures is given in 
Appendix 8 (Section 12.8).
9.3.1.4.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 8 (Section 12.8.3) and all deaths, 
whether or not they are considered SAEs, specific Cardiovascular (CV) and Death 
sections of the eCRF will be required to be completed. These sections include questions 
regarding cardiovascular (including sudden cardiac death) and non-cardiovascular death. 
The CV eCRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms. The CV information should be 
recorded in the specific cardiovascular section of the eCRF within one week of receipt of 
a CV Event data query prompting its completion. 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported.  Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.
9.3.1.5.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs
The events or outcomes listed in the CDC Classification System for HIV-1 Infections 
(Appendix 6, Section 12.6) will be recorded on the HIV-Associated Conditions eCRF 
page if they occur.  However, these individual events or outcomes, as well as any sign, 
symptom, diagnosis, illness, and/or clinical laboratory abnormality that can be linked to 
any of these events or outcomes are not reported to ViiV Healthcare/GSK/Pharmaceutical 
Product Development (PPD) as AEs and SAEs even though such event or outcome may 
meet the definition of an AE or SAE, unless the following conditions apply:

The investigator determines that the event or outcome qualifies as an SAE under part 
‘f’ of the SAE definition (see Section 12.8.2), or

The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual participant, or

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
Death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly.

Lymphomas and invasive cervical carcinomas are excluded from this exemption; 
they must be reported as SAEs even if they are considered to be HIV-related.
9.3.1.6.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to ViiV Healthcare or designee of a SAE 
is essential so that legal obligations and ethical responsibilities towards the 
safety of participants and the safety of a study treatment under clinical 
investigation are met. 

ViiV Healthcare/GSK has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about the safety of a study 
treatment under clinical investigation.  ViiV Healthcare/GSK will comply with 
country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Boards (IRB)/Independent Ethics 
Committees (IEC), and investigators.

Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and ViiV 
Healthcare/GSK policy and forwarded to investigators as necessary.

An investigator who receives an investigator safety report describing a SAE or 
other specific safety information eg, summary or listing of SAE) from ViiV 
Healthcare/GSK will review and then file it along with the Investigator’s 
Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements.
9.3.2.
Pregnancy
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected in addition to the regular pregnancy testing required by 
the protocol.
Details of all pregnancies (intrauterine) in female participants will be collected after the 
start of study treatment and until the final Follow-up visit.  Pregnancies that occur 
following the first dose of study drug will be reported to the Medical Monitor.  Follow-up 
information will be collected for pregnancies occurring from Day 1 to the final Follow-up 
visit.
If a pregnancy is reported, the investigator should inform ViiV Healthcare/GSK/PPD
within  24 hours of learning of the pregnancy and should follow the procedures outlined 
in Section 12.10.2.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form. The pregnancy must be followed up to determine outcome 

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(including premature termination) and status of mother and child(ren). Pregnancy 
complications and elective terminations for medical reasons must be reported as an AE or 
SAE. Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the participant has completed the study and considered by the investigator 
as possibly related to the study treatment must be reported promptly to ViiV 
Healthcare/GSK (or designee).  GSK’s central safety department will forward this 
information to the ART Pregnancy Registry. The international registry is jointly 
sponsored by manufacturers or licensees of ARV products. Additional information and a 
list of participating manufacturers/licensees are available from 
http://www.apregistry.com/.
9.3.3.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs
The events or outcomes listed in the CDC Classification System for HIV-1 Infections 
(Appendix 6, Section 12.6) will be recorded on the HIV-Associated Conditions eCRF 
page if they occur.  However, these individual events or outcomes, as well as any sign, 
symptom, diagnosis, illness, and/or clinical laboratory abnormality that can be linked to 
any of these events or outcomes are not reported to ViiV Healthcare/GSK as AEs and 
SAEs even though such event or outcome may meet the definition of an AE or SAE, 
unless the following conditions apply:

The investigator determines that the event or outcome qualifies as an SAE under part 
‘f’ of the SAE definition (Section 12.8.2) or

The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual participant, or

Death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly.
Lymphomas and invasive cervical carcinomas are excluded from this exemption; they 
must be reported as SAEs even if they are considered to be HIV-related.
If either of the above conditions is met then record the Disease Related Event on the 
SAE page rather than the HIV Associated Conditions eCRF page and report 
promptly to PPD/ViiV Healthcare/GSK.
9.3.4.
Suicidal Risk Monitoring
Participants with HIV infection occasionally may present with symptoms of depression 
and/or suicidality (suicidal ideation or behavior).  In addition, there have been some 
reports of depression, suicidal ideation and behavior (particularly in patients with a 
pre-existing history of depression or psychiatric illness) in some patients being treated 
with INIs, including DTG.  Therefore, it is appropriate and important to monitor 
participants for suicidality before and during treatment. 

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Participants should be monitored appropriately and observed closely for suicidal ideation 
and behavior or any other unusual changes in behavior. It is recommended that the 
investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior. Participants presenting with new 
onset/treatment emergent depression should be advised to contact the investigator 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop, because medical intervention and discontinuation of the study 
medication may be required. Consideration should be given to discontinuing DTG/3TC in 
participants who experience signs of suicidal ideation or behavior.
Assessment of treatment-emergent suicidality will be monitored during this study using 
the electronic version of the Columbia Suicidality Severity Rating Scale (eC-SSRS). The 
definitions of behavioral suicidal events used in this scale are based on those used in the 
Columbia Suicide History Form [Posner, 2007].  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 eC-SSRS is 
to be administered as a patient completed questionnaire specified in the SOA Table 
(Section 2).  The eC-SSRS will be conducted electronically by telephone or by 
computer/tablet connected to the internet.
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the AE (non-serious or SAE) eCRF form 
on any participant that experiences a possible suicidality-related AE while participating 
in this study.  This may include, but is not limited to, an event that involves suicidal 
ideation, a preparatory act toward imminent suicidal behavior, 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 ViiV Healthcare/GSK within 1 week of the investigator 
diagnosing a possible suicidality-related AE.
Families and caregivers of participants being treated with DTG/3TC should be alerted 
about the need to monitor participants for the emergence of unusual changes in behavior, 
as well as the emergence of suicidal ideation and behavior and to report such symptoms 
immediately to the study investigator.
9.4.
Treatment of Overdose
For this study, any tablet intake exceeding the protocol-define daily dose (i.e. 1 tablet) 
will be considered an overdose (see [TIVICAY Product Information, 2020]; [EPIVIR
Product Information, 2020]).  The Investigator should use clinical judgment in treating 
overdose, as ViiV Healthcare/GSK is unable to recommend specific treatment.
For the purposes of this study, an overdose is not an AE (see Section 12.8.1) unless it is 
accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is an SAE (see Section 12.8.2). 

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If the overdose was intentional, please refer to Section 9.3.4 (Suicidal Risk Monitoring) 
which provides instruction for the collection of possible suicidality related AE 
information.
If an overdose occurs and is associated with an adverse event requiring action, all study 
medications should be temporarily discontinued until the adverse event resolves.
In the event of an overdose, the Investigator should:
1.
Contact the Medical Monitor immediately.
2.
Closely monitor the participant for AE/SAE and laboratory abnormalities until 
DTG/3TC can no longer be detected systemically (at least 2 days).
3.
Obtain a plasma sample for PK analysis within 60 hours from the date of the last 
dose of study treatment if requested by the Medical Monitor (determined on a case-
by-case basis).
4.
Document the quantity of the excess dose as well as the duration of the overdosing in 
the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.
9.4.1.
Physical Examinations
Physical exams should be conducted as part of normal routine clinical care but will not be 
collected systematically in the eCRF.  Abnormalities noted during any exam must be 
recorded in the eCRF (e.g. in the current medical conditions or AE logs).
9.4.2.
Electrocardiograms
A 12-lead ECG will be performed at Screening for possible use as a reference during the 
study (i.e. in evaluation of any pertinent cardiovascular event).
9.4.3.
Clinical Safety Laboratory Assessments

The list of clinical laboratory tests to be performed is below; refer to the SoA 
(Section 2) for the timing and frequency.

The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the eCRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition.

All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 5 days after the last dose of study 
treatment should be repeated until the values return to normal or baseline or are 

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no longer considered significantly abnormal by the investigator or medical 
monitor. 

If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified.

All protocol-required laboratory assessments, as defined below must be 
conducted in accordance with the laboratory manual and the SoA.
Table 1
Protocol Required Safety Laboratory Assessments
Hematology:
Platelet count
Automated WBC differential:
RBC count
Neutrophils
WBC count (absolute)
Lymphocytes
Hemoglobin
Monocytes
Hematocrit
Eosinophils
MCV
Basophils
MCH
Clinical Chemistry:
BUN
Potassium
AST
Total bilirubina
Creatinine
Chloride
ALT
Albumin
Glucoseb
Total CO2
Alkaline phosphatase
Creatine phosphokinase
Sodium
Phosphate
GFR/Creatinine clearancec
Calcium
Protein
Cystatin-C (Day 1 only)
Fasting Lipid Paneld
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
Urinalysis
specific gravity, pH, glucose, protein, blood and ketones by dipstick (with microscopic examination if 
blood or protein is abnormal), urine albumin/creatinine ratio, urine protein/creatinine ratio, urine 
phosphate
Other Tests
Plasma HIV-1 RNAe
CD4+ and CD8+ lymphocyte counts (including CD4:CD8 ratio)
Hepatitis B (HBsAg, anti-HBc, anti-HBs, HBV DNA)
Hepatitis C (anti-HCV)
PT/INR 
RPR
HbA1c
Pregnancy test for females of childbearing potentialf
MCV = mean corpuscular volume, RBC = red blood cells, WBC = white blood cells, BUN = Blood urea nitrogen, 
AST=aspartate aminotransferase, ALT = alanine aminotransferase, CO2 = carbon dioxide, HbA1c = glycated 
haemoglobin, HDL = high density lipoprotein, LDL = low density lipoprotein, HbsAg= hepatitis B virus surface 
antigen, PT/INR = prothrombin time/international normalized ratio, RPR = Rapid Plasma Reagin.
a.
Direct bilirubin will be reflexively performed for all total bilirubin values >1.5 × ULN.
b.
For fasting glucose assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments.

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c.
Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Bedside Schwartz 
equation [Schwartz, 2009]. In addition, GFR will be estimated by the central laboratory using Creatinine-
Cystatin C-Based CKiD Equation [Schwartz, 2012] at day 1 and when indicated by renal toxicity criteria.
d.
For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments.
e.
For participants meeting virologic withdrawal criteria, plasma samples will be analyzed in attempt to obtain 
genotype/phenotype data.
f.
Urine pregnancy test/ serum pregnancy test will be performed according to the SoA (Section 2). 
9.5.
Viral Genotyping and Phenotyping
Whole venous blood samples will be obtained from each participant to provide plasma 
for storage samples according to the SoA in Section 2 (for potential viral genotypic and 
phenotypic analyses).  Participants meeting confirmed virologic failure criteria will have 
plasma samples tested for HIV-1 PR and RT genotype and phenotype and HIV-1 
integrase (IN) genotype and phenotype from Baseline samples and from samples 
collected at the time of meeting suspected virologic failure criteria; these results will be 
reported to the investigator as soon as available to provide guidance for election of an 
alternative regimen.
Details concerning the handling, labelling and shipping of these samples will be supplied 
separately.  Genotypic analyses for RT and PR will be carried out at Screening by Q2
Solutions, or Monogram Biosciences if needed due to technical issues, and on-study 
genotypic and phenotypic analyses may be carried out by Monogram Biosciences using, 
but not limited to, their Standard PhenoSense and GenoSure testing methods for RT and 
PR.
9.5.1.
HIV-1 Polymerase Viral Genotyping and Phenotyping
A secondary endpoint of the study will be the incidence of observed genotypic and 
phenotypic resistance to DTG or 3TC and to current ART for participants meeting 
Virologic Withdrawal criteria. The virologic endpoint may also be assessed based on 
third-agent class.
9.5.2.
HIV-1 Exploratory Analyses
To assess the future drug options in participants meeting confirmed virologic failure 
criteria, drugs potentially impacted and remaining available for participants with 
treatment emergent resistance will be evaluated.
After meeting virologic withdrawal criteria, additional analyses for HIV-1 resistance 
may, for example, be carried out on peripheral blood mononuclear cell (whole blood) 
samples collected at Baseline and/or on stored plasma samples from other relevant time 
points.  These analyses may include but are not limited to additional viral genotyping 
and/or phenotyping, as well as other virologic evaluations such as linkage and minority 
species analyses, low level HIV-1 RNA quantitation and measurement of viral replicative 
capacity.  HIV-1 PR and RT genotype and phenotype and HIV-1 integrase genotype and 
phenotype will also be determined on the last on-treatment isolates from participants who 
have HIV-1 RNA 400 c/mL regardless of confirmatory HIV-1 RNA.

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9.6.
Pharmacokinetics
9.6.1.
Blood Sample Collection

Serial (intensive) and sparse blood samples will be collected for measurement of 
plasma concentrations of DTG at the time points specified in the SoA (Section 2) 
and in Section 9.6.2.3. The date and time of dosing and actual date and time of 
each blood sample collection will be recorded. 

Samples will be used to evaluate the plasma PK of DTG and 3TC. For each time 
point identified in SoA, approximately 2 mL of blood will be collected into di-
potassium ethylenediaminetetraacetic acid (K2EDTA) tubes. Details of PK blood 
sample collection, processing, storage and shipping procedures are provided in the 
Investigator site file.

Genetic analyses will not be performed on these blood samples. Participant 
confidentiality will be maintained.
9.6.1.1.
Collection of Sparse PK samples – All Participants
Table 2
Pharmacokinetic Sparse Sample Schedule
Week
Sample Times Relative to Dose
4
1 pre-dosea sample AND
1 sample 2 to 4 hr post doseb
12
1 pre-dose samplea AND
1 sample 4 to 12 hr post doseb
24
1 pre-dose samplea AND
1 sample 12 to 24 hr post dose b
a.
Pre-dose samples will be collected immediately before the dose (i.e. within 15 minutes) which 
will be taken under observation at the clinic.  Pre-dose samples should be collected 20-28 hours 
post previous dose.
b.
All sample timepoints must be obtained from each participant. These samples may be drawn at 
any time during the specified interval.
Note: Participants are to complete a dosing diary card for 3 days prior to PK sampling visit. The PK 
visit should be re-scheduled if the participant took their morning dose prior to coming into the clinic 
on the PK sampling day.  
9.6.1.2.
Collection of Ctrough samples- All Participants
A single sample for analysis of Ctrough will be collected at other clinical visits (i.e. 
Weeks 8, 16, 36, and 48). These samples will be collected immediately prior to dosing 
which will be taken under observation at the clinic.

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9.6.2.
Important Information on collection of PK samples
It is important to collect PK samples according to the specified procedure and timeline.
9.6.2.1.
Timing of sparse PK sample collection
Flexibility is allowed in collecting the post-dose samples (anywhere from 2 to 4 hours 
and 12 to 24 hours post dose) to accommodate participant schedules and so that a range 
of sample times can be obtained.  Participants may choose to remain in clinic until 2 to 4 
hours after taking study medication.  Also, to allow flexibility in scheduling PK draws 
while maintaining quality and accuracy, the week 4, week 12, week 24 samples can be 
drawn interchangeably (i.e. 2 to 4 hours post-dose drawn at week 12 and the 4 to 12 
hours post-dose drawn at week 4) as long as all three samples (2 to 4 hours, 4 to 12 hours, 
and 12 to 24 hours post-dose) are obtained for each participant.
9.6.2.2.
Dosing Diary Cards
To enhance the quality of Ctrough, sparse and intensive PK data collection, participants 
will be asked to complete a dosing diary card with the following information which will 
be included in eCRF:

The date and time of the DTG/3TC FDC administration for 3 days prior to the 
scheduled Ctough, sparse or intensive PK clinic visit;

Whether or not the doses were taken with a meal;

Whether or not the subject vomited within 4 hours of taking the study drug
Three days prior to the scheduled Ctrough, sparse or intensive PK visits, the site 
personnel will contact the participant to remind them:

When their next visit is scheduled, time to arrive at the site and any other practical 
information and instructions with regard to the PK sampling;

To complete all sections of the dosing card for 3 days prior to the visit;

No doses can be missed during the 3 days prior to the scheduled PK visit;

Not take a dose of IP before the clinic visit so that a pre-dose sample can be 
drawn before that days DTG/3TC FDC dose
If a participant presents at clinic for a pre-dose PK sample collection having already 
taken the morning dose or having missed doses within the previous 3 days, it is 
recommended to reschedule PK sampling at the next clinic visit or an ad hoc clinic visit 
for this purpose.  It is not recommended to collect PK samples if date and time of dosing 
for the previous 3 days cannot be reliably confirmed.
9.6.2.3.
Collection of Intensive Serial PK samples
Intensive serial PK samples will be collected in a subset of approximately 12 participants 
to ensure data from 10 evaluable participants at selected sites.  Serial PK sampling should 
be scheduled between Days 5 and 10.  Flexibility is allowed in scheduling serial PK 
collection to accommodate participants’ schedules.

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Additional details on sample collection in this subset of participants is provided in the 
Investigator site file.
Table 3
Pharmacokinetic Serial Intensive Sample Schedule
Day
Sample Times Relative to Dose
5 to 10
Pre-dosea, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24b hours post dose
a.
Pre-dose samples will be collected immediately before the dose (i.e. within 15 minutes) which will be 
taken under observation at the clinic.
b.
Participants in the intensive PK sampling group must return to the site the next morning for the 24-hour 
post dose blood sample collection.
9.6.3.
Sample Analysis
Plasma analysis will be under the control of Platform Technology Services (PTS) PTS 
GlaxoSmithKline, the details of which are provided in the Investigator site file. 
Concentrations of DTG and 3TC will be determined in plasma samples using he currently 
approved bioanalytical methodology. Raw data will be archived at the bioanalytical site 
(detailed in the Investigator site file). 
Analysis of the PK data collected is explained in detail in Section 10.3.3
9.7.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
9.8.
Genetics
Genetics are not evaluated in this study.
9.9.
Biomarkers
Biomarkers are not evaluated in this study.
9.10.
Health Economics
Health Economics/Medical Resource Utilization parameters are not evaluated in this 
study.
10.
STATISTICAL CONSIDERATIONS
10.1.
Sample Size Determination
This study will enroll 30 adolescent participants and is proposed to complement the fully 
powered non-inferiority evaluation of the DTG/3TC combination performed in adults. 
The reported Week 48 response rates for DTG+2NRTIs in adults are 88% to 90% (ITT-
E, % <50 c/mL by Snapshot algorithm). It is therefore reasonable to conservatively 

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expect a lower response rate of 77% (23/30) or 80% (24/30) in adolescents based on their 
recognized treatment adherence difficulties. 
A single arm study with 30 participants will provide an exact Clopper Pearson 95% CI of 
61%-92% for an assumed response rate of 80% (% <50 c/mL by Snapshot algorithm at 
Week 48). The study will provide an exact Clopper Pearson 95% CI of 58%-90% if the 
assumed response rate is 77% (% <50 c/mL by Snapshot algorithm at Week 48).
10.2.
Populations for Analyses
For purposes of analysis, the following populations are defined:
10.2.1.
Intent-to-Treat Exposed (ITT-E) Population
This population will consist of all enrolled participants who receive at least one dose of 
study medication. Unless stated otherwise, the ITT-E Population will be used for efficacy 
analyses.
10.2.2.
Per Protocol (PP) Population
This population will consist of participants in the ITT-E Population with the exception of 
major protocol violators: e.g., violations which could affect the assessment of antiviral 
activity; this will be defined in the RAP. The PP population will be used for sensitivity 
analyses of the primary efficacy measure.
10.2.3.
Safety Population
The Safety Population is defined as all participants who receive at least one dose of study 
medication. Participants will be analyzed according to the actual treatments received. 
Unless otherwise stated, the Safety Population will be used for safety analyses.
10.2.4.
Pharmacokinetic Populations
Sparse PK population is defined as all participants who received at least 1 dose of 
DTG/3TC and have evaluable sparse samples with drug concentrations reported.
Intensive PK population is defined as the subset of participants enrolled into intensive PK 
sampling, who received at least 1 dose of DTG/3TC and have evaluable drug 
concentrations reported.
The defining of evaluable drug concentrations and further details on the PK populations 
will be described in the reporting and analysis plan (RAP).
10.2.5.
Analysis Data Sets
The primary analysis set of data is based on virologic failure and success as defined by 
the FDA snapshot MSDF (Missing, Switch of Discontinuation = Failure) algorithm. With 

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the exception below, virologic failure includes participants who changed any component 
of background therapy to a new drug class, changed background components that were 
not permitted per protocol, or changed any background drug in the regimen because of 
lack of efficacy (perceived or documented) before Week 48; patients who discontinued 
study drug or study before Week 48 for lack or loss of efficacy and patients who are 
equal to or above 50 c/mL in the 48-week window. This will also be reported by study 
visit. This algorithm treats all participants without HIV-1 RNA data at the visit of interest 
(due to missing data or discontinuation of IP prior to visit window) as non-responders, as 
well as participants who switch their concomitant ART prior to the visit of interest, since 
no switches (with the exception below) are allowed in the protocol.
Otherwise, virologic success or failure will be determined by the last available HIV-1 
RNA assessment while the participant is on-treatment within the visit of interest window 
(to be specified in the RAP).  Full details of this snapshot algorithm will be contained in 
the RAP.
Another secondary set of data will treat participants as censored if they discontinue for 
reasons other than those related to treatment (AEs, tolerability and lack of efficacy). This 
data set will be the Treatment Related Discontinuation = Failure (TRDF) data set.
The observed case (OC) dataset, which uses only data that are available at a particular 
time point with no imputation for missing values, will be the primary dataset for 
assessing safety and will also be used for some analyses of efficacy.
Further details will be provided in the RAP.
10.3.
Statistical Analyses
10.3.1.
Efficacy Analyses
All efficacy analyses will be performed on the IIT-E and per protocol populations.
The primary endpoint of the proportions of participants meeting the criteria for virologic 
success as defined by the FDA snapshot algorithm will be reported with exact Clopper 
Pearson 95% confidence intervals.
Change in CD4/8 count and percent from baseline to weeks 24 and 48 will be bounded by 
95% confidence intervals.
Further details including details on the week 96 and 144 analyses will be provided in the 
RAP.
10.3.2.
Safety Analyses
All safety analyses will be performed on the Safety Population. 
Exposure to study medication, measured by the number of weeks on study drug, will be 
summarized.  The proportion of participants reporting AEs will be tabulated.  The 
following summaries of AEs will be provided:

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
Incidence and severity of all AEs

Incidence and severity of treatment related AEs

Incidence and severity of AEs leading to withdrawal

Incidence of SAEs

Cumulative incidence of AEs by time to first occurrence

Cumulative incidence of treatment related AEs by time to first occurrence
Laboratory data will be summarized by visit. In addition, the number and percentage of 
participants with graded laboratory toxicities (based on Division of AIDS [DAIDS] 
categories) will be summarized. The proportion of participants experiencing changes 
from Baseline in their National Cholesterol Education Program (NCEP) lipid categories 
will be summarized. Further details of safety analyses will be included in the RAP.
10.3.3.
Pharmacokinetic Analyses
10.3.3.1.
Intensive Pharmacokinetic Analyses
PK analyses will be the responsibility of Clinical Pharmacology Modeling and 
Simulation department within GSK or their designee. 
For participants participating in serial sampling, plasma DTG and 3TC concentration-
time data will be analyzed by non-compartmental methods with Phoenix WinNonlin 
version 4.1 or higher. Calculations will be based on the actual sampling times recorded
during the study. From the plasma concentration-time data, the following 
pharmacokinetics parameters will be determined as data permit:

Maximum observed plasma concentration (Cmax)

Time of maximum observed plasma concentration (tmax)

Area under the plasma concentration-time curve [AUC from time zero (pre-
dose) to last time of quantifiable concentration, AUC(0-t) and AUC over the 
dosing interval, AUC(0-)] 

Apparent terminal half-life (t1/2)

Observed pre-dose (trough) concentration (C0)

Observed plasma concentration at the end of a dosing interval (e.g. 
concentration at 24 hours) (C24)
Any additional PK parameters that are calculated will be provided in the RAP. 
Results based on samples collected from a participant with emesis within 4 hours of the 
dose will not be considered. 
All PK data will be stored in the R&D archives, GSK. 

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Statistical analyses of the PK parameter data will be the responsibility of the study 
sponsor and/or its delegate services provider. Details of the statistical analysis will be 
provided in the RAP. An outline is provided below: 
PK data will be presented in graphical and tabular form and will be summarized 
descriptively. Plasma DTG concentration-time data will be listed by participant and time 
point and summarized descriptively at each time point. Individual participant profiles for 
DTG concentration-time data will be presented on both a linear and semi-log scale. Plots 
on the linear and semi-log scale for mean and median DTG plasma concentrations versus 
time will also be generated. Plasma DTG parameters will be log-transformed prior to 
analysis.
10.3.3.2.
Sparse Pharmacokinetic Analysis
Sparse plasma concentration-time data collected in all participants may be combined with 
serial data and pooled with data from other studies to perform an integrated population 
PK analysis. Further details of the population PK analysis will be provided in the RAP. If 
performed, this analysis will be reported separately. 
10.3.4.
Other Analyses
All other analyses will be described in the reporting and analysis plan.
Additionally, special statistical and data analysis considerations may be warranted in the 
event that the COVID-19 or related epidemics or natural disasters may affect the study 
and data integrity. To the extent possible, these will be described in the main study RAP; 
alternatively, a separate RAP focusing on modified data handling rules (e.g., changes to 
analysis populations, visit windows and endpoints) and analyses (e.g., sensitivity analyses 
to assess impact of and account for missing data) may be prepared, taking into account 
applicable regulatory guidance and best practices for handling such situations.
10.3.5.
Secondary Analyses
At least three analyses will be conducted to evaluate primary and secondary objectives of
the protocol, one when all subjects have completed their visits at Week 48, at Week 96, 
and at Week 144. Further data cuts and analyses may be conducted as
necessary after Week 144, in the Continuation Phase, to support regulatory submissions 
and publications.
The Week 48 analysis will be primary. No adjustment for multiplicity caused by
repeated evaluation of the primary endpoint will be made as the Week 96, and
Week 144 analyses will be secondary. 
An IDMC will be instituted to ensure external objective medical and/or statistical review
of efficacy and safety in order to protect the ethical interests and well-being of subjects
and to protect the scientific validity of this study. An initial IDMC data look will occur 
after 3 participants complete the Week 12 visit. Subsequent meetings will occur 
approximately once every 6 months with potential for additional ad-hoc meetings. Ad-
hoc reviews of data by the IDMC may be triggered whenever the number of CVWs 

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exceeds thresholds pre-specified in the IDMC charter. Full details of the methods, timing, 
decision criteria and operating characteristics will be pre-specified in the IDMC Charter.

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11.
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GlaxoSmithKline Document Number 2017N352880_00: GSK1349572 (Dolutegravir) 
Clinical Investigator's Brochure, version 11, supplement 01. December 2017
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GlaxoSmithKline Document Number RM2007/13: GSK1349572 (Dolutegravir) Clinical 
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International Antiviral Society (IAS)-USA Antiretroviral Treatment of Adult HIV 
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Günthard HF, Saag MS, Benson CA, et al. JAMA.2018; 320(4):379-396.
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Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification 
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FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 
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Reynes J, Lawal A, Pulido F, et al. Examination of noninferiority, safety, and tolerability 
of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/ 
emtricitabine in antiretroviral-naive subjects: the PROGRESS study, 48-week results. 
HIV Clin Trials. 2011;12:255-267.
Reynes J, Meftah N, Tuaillon E, et. al. Dual regimen with Dolutegravir and Lamivudine 
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HIV Science, 23 – 26 July 2017, Paris, France, Abstract .
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Schwartz GJ, Schneider MF, Maier PS, et al. Improved equations estimating GFR in 
children with chronic kidney disease using an immunonephelometric determination of 
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Stellbrink H.-J, Pulik P, Szlavik J, MurphyD, Lazzarin A, Portilla J, et. al.Maraviroc 
(MVC) dosed once daily with darunavir/ritonavir (DRV/r) in a 2 drug-regimen compared 
to emtricitabine/tenofovir (TDF/FTC) with DRV/r; 48-week results from MODERN 
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Taiwo BO, Zheng L, Nyaku AN, et. al. ACTG A5353: A pilot study of dolutegravir 
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TIVICAY (dolutegravir) Product Insert.  Available at: 
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among patients with syphilis in the era of the HIV infection epidemic: incidence and risk 
factors. Clin Infect Dis. 2010; 51: 976–979

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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
3TC
Lamivudine, EPIVIR
ABC
Abacavir, ZIAGEN
ABC/3TC
Abacavir/lamivudine, EPZICOM, KIVEXA
AE
Adverse event
AIDS
Acquired immunodeficiency syndrome
ALT
Alanine aminotransferase
Anti-HBc
Hepatitis B core antibody
Anti-HBs
Hepatitis B surface antibody
ARV
Antiretroviral
ART
Antiretroviral therapy
AST
Aspartate aminotransferase
AUC
Area Under the Curve
B
Baseline
C
Continuation phase
CDC
Centers for Disease Control and Prevention
cm
Centimeter
CMO
Chief Medical Officer
COVID-19
Coronavirus Disease 2019
CrCl
Creatinine clearance
CRF
Case report form
CVW
Confirmed virologic withdrawal
DAIDS
Division of Acquired Immunodeficiency Syndrome
DNA
Deoxyribonucleic acid
DTG
Dolutegravir, TIVICAY
DTG/3TC
Dolutegravir/lamivudine, DOVATO
dL
Deciliter
E
Extension Phase Visit
EC
End of Continuation Phase Visit
ECG
Electrocardiogram
eCRF
electronic Case report form
eC-SSRS
electronic Columbia Suicidality Severity Rating Scale
EU
European Union
F
Follow-up Visit
FDA
Food and Drug Administration
FDC
Fixed-dose combination
FRP
Females of reproductive potential
GCP
Good clinical practice
eGFR
Estimated Glomerular filtration rate
GSK
GlaxoSmithKline
Hb1Ac
Glycated hemoglobin

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HBsAb
Hepatitis B surface antibody
(anti)-HBc
Hepatitis B core antibody
HBV
Hepatitis B virus
hCG
Human chorionic gonadotrophin
HCV
Hepatitis C virus
IDMC
Independent data monitoring committee
IN
Integrase
INR
International normalized ratio
INSTI
Integrase strand transfer inhibitor
ITT
Intent to treat
IVRS/IWRS
Interactive voice/web response system
mL
Milliliter
Min
Minute
NNRTI
Non-nucleoside reverse transcriptase inhibitor
NRTI
Nucleoside reverse transcriptase inhibitor
PEP
Post-exposure prophylaxis
PrEP
Pre-exposure prophylaxis
PI
Protease inhibitor
PK
Pharmacokinetic
PMTCT
Prevention of mother to child transmission
PPD
Pharmaceutical Product Development
PR
Protease
RAL
Raltegravir
RAP
Reporting and analysis plan
RNA
Ribonucleic acid
RPR
Rapid plasma reagin
RT
Reverse transcriptase
RTV
Ritonavir
SAE
Serious adverse event
SC
Screening Visit
STR
Single tablet regimen
SVW
Suspected virologic withdrawal
TDF/FTC
Tenofovir disoproxil fumarate/ emtricitabine
ULN
Upper limit of normal
VSLC
ViiV Healthcare safety and labelling committee
W
Withdrawal Visit
WHO
World Health Organization
ZDV
Zidovudine, RETROVIR
ZDV/3TC
Zidovudine/lamivudine, COMBIVIR

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Trademark Information
Trademarks of the ViiV Healthcare 
group of companies
Trademarks not owned by the ViiV 
Healthcare group of companies
COMBIVIR
GenoSure
DOVATO
MedDRA
EPIVIR
PhenoSense
EPZICOM
WinNonlin
KIVEXA
TIVICAY
TRIZIVIR

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12.3.
Appendix 3: Liver Safety Required Actions and Follow up 
Assessments
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 INR>1.5, if INR measured
Cannot 
Monitor
ALT 5xULN but <8xULN and cannot 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 3xbaseline (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 discontinue study treatment.

Report the event to the Medical Monitor
within 24 hours.

Complete the liver event eCRF and 
complete an SAE data collection tool if the 
event also meets the criteria for an SAE2.

Complete the liver imaging and/or liver 
biopsy eCRFs if these tests are performed.

Perform liver event follow up assessments. 

Monitor the participant until liver chemistries 
resolve, stabilise, or return to within 
baseline (see MONITORING below).

Do not restart participant with study 
treatment unless allowed per protocol and 
VSLC approval is granted (refer to 
Appendix 5, Section 12.5– Liver Safety –
Study Treatment Restart of Rechallenge 
Guidelines).

Viral hepatitis serology, including:

Hepatitis A immunoglobulin M (IgM) 
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 
eCRF

Serum acetaminophen adduct HPLC 
assay (quantifies potential 

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
If restart is not allowed or not granted, 
permanently discontinue study treatment 
and may continue participant in the study 
for any protocol specified follow up 
assessments.
MONITORING:

Make every reasonable attempt to have 
participants return to clinic within 24 hours
for repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver event follow up assessments 
(at the central laboratory) as described to 
the right. 

Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline.

A specialist or hepatology consultation is 
recommended.
acetaminophen contribution to liver injury 
in participants with definite or likely 
acetaminophen use in the preceding 
week [James, 2009]).  The site must 
contact the Medical Monitor when this 
test is required.

Blood sample for pharmacokinetic (PK) 
analysis, obtained within 60 hours of last 
dose4.

Serum CPK and lactate dehydrogenase 
(LDH).

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 (IgG or gamma 
globulins).

Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms.

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, fatigue, decreased 
appetite, nausea, vomiting, abdominal 
pain, jaundice, fever, or rash as relevant 
on the AE report form.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant 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) must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); INR measurement is not required, and the threshold 
value stated will not apply to participants 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).
4.
Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to 
blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the Investigator site file

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Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
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 participant 
safety.

Participant can continue study treatment

Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until resolution, stabilisation (ALT 
<5×ULN on 2 consecutive evaluations) or return 
to within baseline

If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above

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12.4.
Appendix 4: Study Governance Considerations
12.4.1.
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 participants begins.
12.4.2.
Regulatory and Ethical Considerations
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines

Applicable ICH Good Clinical Practice (GCP) Guidelines

Applicable laws and regulations
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC

Notifying the IRB/IEC of SAE or other significant safety findings as required by 
IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 

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Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
12.4.3.
Informed Consent and Assent Process

The investigator or his/her representative will explain the nature of the study to 
the participant and his/her legally authorized guardian.

Participants must be informed that their participation is voluntary. Each 
participant’s legally authorized guardian (or the participant as required by local 
law) will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center. 

Where appropriate, participants must also provide written assent for 
participation in the study.  The written assent form will meet requirements of 21 
CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC 
or study center.

The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF.

Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 

As participants meet what is considered the age of majority in the country (e.g. 
18 years of age), they must sign the currently approved informed consent form 
to continue in the study.

A copy of the ICF(s) must be provided to the participant and the participant’s 
legally authorized guardian.

Participants who are rescreened or who restart study medication after 
temporarily stopping for toxicity management are required to sign a new ICF.
The informed consent process will include information exchange, detailed discussion, 
and assessment of understanding of all required elements of informed consent, including 
the potential risks, benefits, and alternatives to study participation. Written informed 
consent must be obtained from the participant (or parents or legal guardians of 
participants who cannot consent for themselves, such as those below the legal age). The 
participant's assent must also be obtained if he or she is able to understand the nature, 
significance, and risks of the study. The informed consent will describe the purpose of the 
study, the procedures to be followed, and the risks and benefits of participation. A copy 
of the consent form will be given to the participant (or parent or legal guardian).

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It is generally expected that only one parent or legal guardian will provide informed 
consent for the child’s participation in this study. However, parental consenting 
requirements at each site will depend on the IRB/IEC risk determination.
Should the parent or legal guardian of an enrolled child die or no longer be available for 
any reason, no further study-specific visits or procedures may be performed until 
informed consent for continued study participation is obtained from a locally authorized 
guardian. Study sites should establish and maintain written procedures describing the 
standards that will be followed to identify who may serve as guardian for an enrolled 
adolescent, reflective of applicable IRB/IEC guidance for conduct of human participants 
research within the context of available local law, regulation, or government policy.
Children who are wards of State or any other agency, institution or entity are excluded 
from enrollment into this study.  The site Investigator must notify the Study Medical 
Monitor immediately if a participant's guardianship status changes such that they become 
a ward during the study. If this occurs, the ViiV Chief Medical Officer must determine if 
the participant may continue in the study. 
12.4.4.
Data Protection

Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 

The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant. 

The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities.
12.4.5.
Independent Data Monitoring Committee
Because a dual regimen of DTG/3TC represents a new treatment paradigm for HIV 
infection, an IDMC will be used in this study to ensure external objective medical and/or 
statistical review of safety and/or efficacy issues in order to protect the ethical and safety 
interests of participants and to protect the scientific validity of this study.  The schedule 
of the analysis plan for IDMC review is described in the IDMC charter, which is 
available upon request.
All communications received from the IDMC regarding the status of the study will be 
shared with investigators in a timely manner.

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12.4.6.
Dissemination and Publication of Clinical Study Data
12.4.6.1.
Dissemination of Study Data
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The Investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a ViiV Healthcare/GSK site or other 
mutually-agreeable location.
ViiV Healthcare/GSK will also provide the investigator with the full summary of the 
study results.  The Investigator is encouraged to share the summary results with the study 
participants, 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 with ViiV 
Healthcare/GSK Policy.
12.4.6.2.
Publication of Study Data
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments. 
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement.
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.
12.4.7.
Data Quality Assurance and Control
12.4.7.1.
Quality Assurance

All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (eg, laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF. 

The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. To 
ensure compliance with GCP and all applicable regulatory requirements, ViiV 
Healthcare/GSK/PPD 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. 

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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.
12.4.7.2.
Quality Control
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. The investigator and the head of the medical institution 
(where applicable) agrees to allow the monitor direct access to all relevant documents.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
In accordance with applicable regulations including GCP, and PPD procedures, PPD 
monitors will contact the site 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 
ViiV Healthcare, GSK or PPD requirements.
When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the eCRF will serve 
as the source document.
PPD will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of participants are being protected.

Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements.
12.4.8.
Source Documents and Retention
12.4.8.1.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site.
All participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (eg, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. Data reported on the eCRF or entered in the eCRF that 
are transcribed from source documents must be consistent with the source documents or 

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the discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current medical 
records must be available.
12.4.8.2.
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 Healthcare/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.
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final Clinical Study 
Report (CSR)/ equivalent summary unless local regulations or institutional policies 
require a longer retention period. No records may be destroyed during the retention 
period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
The investigator must notify ViiV Healthcare, GSK or PPD 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.
12.4.9.
Study and Site Closure
Upon completion or premature discontinuation of the study, the PPD monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and PPD Standard Operating 
Procedures.
ViiV Healthcare/GSK reserves the right to close the study site or terminate the study at 
any time for any reason at the sole discretion of ViiV Healthcare/GSK. For multicenter 
studies, this can occur at one or more or at all sites. Reasons for early closure of a study 
may include safety or ethical issues or severe non-compliance.  Reasons for early closure 
of a study site by the sponsor or investigator may include but are not limited to:

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
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study treatment development
Study sites will be closed upon study completion. A study site is considered closed when 
all required documents and study supplies have been collected and a study-site closure 
visit has been performed.

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12.5.
Appendix 5: Liver Safety – Study Treatment Restart or 
Rechallenge Guidelines
If a participant meets liver chemistry stopping criteria, do not restart/rechallenge 
participant with study treatment unless:

ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted

Ethics and/or IRB approval is obtained, if required, and

Separate consent for treatment restart/rechallenge is signed by the participant
If VSLC approval to restart/rechallenge participant with study treatment is not granted, 
then participant must permanently discontinue study treatment and may continue in the 
study for protocol-specified follow up assessments.
12.5.1.
Drug Rechallenge Following Liver Events that are Possibly 
Related to IP
Following drug-induced liver injury, drug rechallenge is associated with a 13% 
mortality across all drugs in prospective studies [Andrade, 2009]. Clinical outcomes 
vary by drug, with nearly 50% fatality with halothane readministered within one month 
of initial injury. However, some drugs seldom result in recurrent liver injury or fatality.  
Risk factors for a fatal drug rechallenge outcome include:

Hypersensitivity [Andrade, 2009] with initial liver injury (e.g. fever, rash, 
eosinophilia) 

jaundice or bilirubin >2xULN with initial liver injury (direct bilirubin >35% of 
total)

participant currently exhibits severe liver injury defined by: ALT 3xULN, 
bilirubin 2xULN (direct bilirubin >35% of total), or INR1.5

serious adverse event or fatality has earlier been observed with drug 
rechallenges [Hunt, 2010; Papay, 2009]

evidence of drug-related preclinical liability (e.g. reactive metabolites; 
mitochondrial impairment [Hunt, 2010].
Rechallenge refers to resuming study treatment following drug induced liver injury 
(DILI). Because of the risks associated with rechallenge after DILI this should only be 
considered for a participant for whom there is compelling evidence of benefit from a 
critical or life-saving medicine, there is no alternative approved medicine available, and a 
benefit:risk assessment of rechallenge is considered to be favourable.
Approval by the VSLC for drug rechallenge can be considered where:

Principal Investigator (PI) requests consideration of rechallenge with study 
treatment for a participant is receiving compelling benefit, benefit of drug restart 
exceeds risk, and no effective alternative therapy is available.  Ethics Committee 

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or Institutional Review Board approval of drug restart/rechallenge must be 
obtained, as required.

If the restart/rechallenge is approved by the VSLC in writing, the participant 
must be provided with a clear description of the possible benefits and risks of 
drug administration, including the possibility of recurrent, more severe liver 
injury or death.

The participant must also provide signed informed consent specifically for the 
IP restart/rechallenge. Documentation of informed consent must be recorded in 
the study chart.

Study drug must be administered at the dose specified by the VSLC.

Participants approved by the VSLC for rechallenge of IP must return to the 
clinic twice a week for liver chemistry tests for a minimum of one month and 
thereafter for as long as clinically indicated and then laboratory monitoring may 
resume as per protocol. 

If after study treatment rechallenge, participant meets protocol defined liver 
chemistry stopping criteria, study drug must be permanently discontinued.

The Medical Monitor and the Ethics Committee or Institutional Review Board 
as required, must be informed of the participant’s outcome following study 
treatment rechallenge

Any adverse events should be recorded on the appropriate eCRF(s), and reported 
where applicable, as per Section 9.3.1.1.
12.5.2.
Drug Restart Following Transient Resolving Liver Events Not 
Related to IP
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g. biliary obstruction, 
pancreatic events, hypotension, acute viral hepatitis). Furthermore, there should be no 
evidence of alcoholic hepatitis or hypersensitivity, and the study treatment should not be 
associated with HLA markers of liver injury.
Approval by the VSLC for drug restart can be considered where:

Investigator requests consideration for study treatment restart if Liver 
chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension 
and liver chemistries have improved to normal or are within 1.5 x baseline and 
ALT <5xULN). 

Furthermore, there should be no evidence of fever, rash, eosinophilia, 
hypersensitivity, alcoholic hepatitis or possible study treatment-induced liver, 
and the drug should not be associated with HLA markers of liver injury.  (If 
restart of TRIUMEQ or any other abacavir- containing product is being 
considered then the Participant must be HLA-B*5701 negative).

Ethics Committee or Institutional Review Board approval of drug 
restart/rechallenge must be obtained, as required.

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
If restart of drug is approved by the VSLC in writing, the participant must be 
provided with a clear description of the possible benefits and risks of drug 
administration, including the possibility of recurrent, more severe liver injury or 
death.

The participant must also provide signed informed consent specifically for the 
restart.  Documentation of informed consent must be recorded in the study chart.

Study drug must be administered at the dose specified by the VSLC.

Participants approved by the VSLC for restarting IP must return to the clinic 
once a week for liver chemistry tests for a minimum of one month and thereafter 
for as long as clinically indicated and then laboratory monitoring may resume as 
per protocol.  

If after study treatment re-start, participant meets protocol-defined liver 
chemistry stopping criteria, follow usual stopping criteria instructions.

The Medical Monitor and the Ethics Committee or Institutional Review Board 
as required, must be informed of the participant’s outcome following study 
treatment restart

Any adverse events should be recorded on the appropriate eCRF(s), and reported 
where applicable, as per Section 9.3.1.1.
References:
Andrade RJ, Robles M, Lucena MI.  Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf. 2009;8:709-714.
Hunt, CM.  Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review.  Hepatol. 2010;52:2216-
2222.
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, Hunt CM.  Drug-induced liver 
injury following positive drug rechallenge.  Regul Tox Pharm. 2009;54:84-90.

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12.6.
Appendix 6: CDC Classification and WHO Staging for HIV-1 
Infection
12.6.1.
CDC Classification for HIV-1 Infection
Note that the CD4+ T-lymphocyte count takes precedence over the CD4+ T-lymphocyte 
percentage in HIV infection stages 1, 2, and 3.  The CD4+ T-lymphocyte percentage 
should only be considered if the count is missing.
HIV infection, stage 0
Indicates early HIV infection, inferred from a negative or indeterminate HIV test result 
within 180 days of a positive result.  The criteria for stage 0 supersede and are 
independent of criteria used for other stages.
HIV infection, stage 1

Laboratory confirmation of HIV infection with no AIDS-defining condition, and
o
CD4+ T-lymphocyte count of ≥500 cells/L, or
o
CD4+ T-lymphocyte percentage of total lymphocytes of ≥26%.
HIV infection, stage 2

Laboratory confirmation of HIV infection with no AIDS-defining condition, and
o
CD4+ T-lymphocyte count of 200 to 499 cells/L, or
o
CD4+ T-lymphocyte percentage of total lymphocytes of 14% to 25%.
HIV infection, stage 3 (AIDS)

Laboratory confirmation of HIV infection, and
o
CD4+ T-lymphocyte count of <200 cells/L, or
o
CD4+ T-lymphocyte percentage of total lymphocytes of <14%, or
o
Documentation of an AIDS-defining condition (see below).
Documentation of an AIDS-defining condition supersedes a CD4+ T-lymphocyte count 
of >200 cells/L and a CD4+ T-lymphocyte percentage of total lymphocytes of >14%.
HIV infection, stage unknown

Laboratory confirmation of HIV infection, and
o
No information on CD4+ T-lymphocyte count or percentage, and
o
No information on presence of AIDS-defining conditions.
Category C-defining opportunistic illnesses in HIV infection

Candidiasis of bronchi, trachea, or lungs 

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
Candidiasis of oesophagus

Cervical cancer, invasive

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (>1 month's duration)

Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or 
oesophagitis (onset at age >1 month)

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month's duration)

Kaposi's sarcoma

Lymphoma, Burkitt's (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or Mycobacterium kansasii, disseminated or 
extrapulmonary

Mycobacterium tuberculosis of any site, pulmonary, disseminated or extrapulmonary 

Mycobacterium, other species or unidentified species, disseminated or 
extrapulmonary

Pneumocystis jirovecii pneumonia

Pneumonia, recurrent

Progressive multifocal leukoencephalopathy

Salmonella septicaemia, recurrent

Toxoplasmosis of brain, onset at age >1 month

Wasting syndrome attributed to HIV.
Reference:
Centers for Disease Control and Prevention. 1993 revised classification system for HIV 
infection and expanded surveillance case definition for AIDS among adolescents and 
adults. MMWR Recomm Rep. 1992 Dec 18;41(RR-17):1-19. Available at: 
https://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm. Accessed December 4, 
2017.

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12.6.2.
World Health Organization. WHO Classification of HIV-Related 
Disease in Adults and Adolescents
Clinical Stage 1

Asymptomatic
Persistent generalized lymphadenopathy
Clinical Stage 2

Moderate unexplained weight loss (<10% of presumed or measured body weight)a

Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media and 
pharyngitis)

Herpes zoster

Angular cheilitis

Recurrent oral ulceration

Papular pruritic eruptions

Seborrhoeic dermatitis

Fungal nail infection
Clinical Stage 3

Unexplainedb severe weight loss (>10% of presumed of measured body weight)

Unexplained chronic diarrhoea for longer than one month

Unexplained persistent fever (above 36.7°C intermittent or constant for longer than 
one month)

Persistent oral candidiasis

Oral hairy leukoplakia

Pulmonary tuberculosis (current)

Severe bacterial infections (such as pneumonia, empyema, pyomyositis, bone or joint 
infection, meningitis or bacteraemia)

Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 x 109 per litre) or chronic 
thrombocytopaenia (<50 x 109 per litre)
Clinical Stage 4c

HIV wasting syndrome

Pneumocystis pneumonia

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
Recurrent sever bacterial pneumonia

Chronic herpes simplex infection (orolabial, genial or anorectal of more than one 
month’s duration or visceral at any site)

Oesophageal candidiasis (or candidiasis or trachea, bronchi or lungs)

Extrapulmonary tuberculosis

Kaposi’s sarcoma

Cytomegalovirus infection (retinitis or infection of other organs)

Central nerous system toxoplasmosis

HIV encephalopathy

Extrapulmonary cryptococcosis including meningitis

Disseminate non-tuberculous mycobacterial infection

Progressive multifocal leukoencephalopathy

Chronic cryptosporidiosis (with diarrhoea)

Chronic isosporiasis

Disseminated mycosis (coccidiomycosis or histoplasmosis)

Recurrent non-typhoidal Salmonella bacteraemia

Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated tumours

Invasive cervical carcinoma

Atypical disseminated leishmaniasis

Symptomatic HIV-associated nephropathy or symptomatic HIV-associated 
cardiomyopathy
a Assessment of body weight in pregnant woman needs to consider the expected weight gain of pregnancy
b Unexplained refers to where the condition Is not explained by other causes
c Some additional specific conditions can also be included in regional classifications (such as reactivation 
of American trypanosomiasis [meningoencephalitis and/or myocarditis]) in the WHO Region of the 
Americas and disseminated penicilliosis in Asia).
Reference:
World Health Organization. WHO Case Definitions of HIV for Surveillance and Revised 
Clinical Staging and Immunological Classification of HIV-Related Disease in Adults and 
Children. 2007. Available at:
http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf?ua=1. Accessed 
December 4, 2017.

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12.8.
Appendix 8: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
12.8.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment.

NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study treatment.
Events Meeting the AE Definition 

Any abnormal laboratory test results (hematology, clinical chemistry, or
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not 
related to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition of 
an AE or SAE.
Events NOT Meeting the AE Definition 

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition.

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
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
12.8.2.
Definition of Serious Adverse Event
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
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, 
which hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.

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e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
g.
Is associated with liver injury and impaired liver function defined as:
ALT 3xULN and total bilirubin* 2xULN (>35% direct), or
ALT 3xULN and INR** > 1.5.
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT 3xULN and total bilirubin 2xULN, then the event is still to be reported as an 
SAE.
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to 
be recorded on the SAE form.
12.8.3.
Definition of Cardiovascular Events
Cardiovascular Events (CV) Definition:
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs:

Arrhythmias

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization

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12.8.4.
Sentinel Events
Sentinel Event Definition:
A sentinel event is a GSK/VHC-defined SAE that is not necessarily drug-related but 
has been associated historically with adverse reactions for other drugs and is therefore 
worthy of heightened pharmacovigilance. Medical Monitor review of all SAEs for 
possible sentinel events is mandated at GSK/VHC. The Medical Monitor may request 
additional clinical information on an urgent basis if a possible sentinel event is 
identified on SAE review. The current GSK/VHC-defined sentinel events are listed 
below:

Acquired Long QT Syndrome

Agranulocytosis/Severe neutropenia 

Anaphylaxis and anaphylactoid reactions 

Hepatotoxicity

Acute renal failure

Seizure

Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN)
12.8.5.
Recording and Assessing AE and SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to ViiV Healthcare/GSK in lieu of completion of the ViiV 
Healthcare/GSK /AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by ViiV Healthcare/GSK. In this case, all participant identifiers, with 
the exception of the participant number, will be redacted on the copies of the 
medical records before submission to ViiV Healthcare/GSK.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.

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Assessment of Intensity
Every AE and SAE reported during the trial should be evaluated by the investigator 
and graded in the eCRF according to the DAIDS toxicity scales (see Appendix 7). 
Note: Grade 4 DAIDS toxicity grades for laboratory parameters that are asymptomatic 
would not necessarily be considered SAEs, a clinical correlation would be necessary.
Where a DAIDS toxicity scale is not available for a particular event or parameter, then 
the investigator will instead make an assessment of intensity using one of the following 
categories:
1. Mild:  An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.
2. Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities.
3. Severe:  An event that prevents normal everyday activities. - an AE that is assessed 
as severe will not be confused with an SAE. Severity is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality

The investigator is obligated to assess the relationship between study treatment 
and each occurrence of each AE/SAE.

A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to ViiV Healthcare/GSK. 
However, it is very important that the investigator always make an assessment 
of causality for every event before the initial transmission of the SAE data to 
ViiV Healthcare/GSK.

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
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by ViiV 
Healthcare/GSK to elucidate the nature and/or causality of the AE or SAE as fully 
as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide ViiV Healthcare/GSK with a copy 
of any post-mortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to ViiV Healthcare/GSK 
within 24 hours of receipt of the information.
12.8.6.
Reporting of SAE to ViiV Healthcare/GSK/PPD
SAE Reporting to ViiV Healthcare/GSK/PPD via Electronic Data Collection Tool

The primary mechanism for reporting SAE to ViiV Healthcare/GSK/PPD will be 
the electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the Medical Monitor by telephone.

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
Contacts for SAE reporting can be found on the Sponsor/Medical Monitor Contact 
Information Page of this protocol.
SAE Reporting to ViiV Healthcare/GSK/PPD via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the Medical Monitor.

In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames.

Contacts for SAE reporting can be found on the Sponsor/Medical Monitor Contact 
Information Page of this protocol.
Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
“SAE” data 
collection tool
24 hours
Updated “SAE” data 
collection tool
Cardiovascular or 
death event
Initial and 
follow-up 
reports to be 
completed 
when the 
cardiovascular 
event or death 
is reported 
“CV events” and/or 
“death” data 
collection tool(s) if 
applicable
Initial and follow-up 
reports to be 
completed when 
the cardiovascular 
event or death is 
reported
Updated “CV events” 
and/or “death” data 
collection tool(s) if 
applicable
Pregnancy
24 hours
“Pregnancy 
Notification Form”
24 hours 
“Pregnancy Follow-
up Form”
ALT 3×ULN and
bilirubin 2×ULN 
(>35% direct)
24 hoursa
“SAE” data 
collection tool. 
“Liver Event eCRF” 
and “Liver Imaging” 
and/or “Liver 
Biopsy” eCRFs, if 
applicableb
24 hours
Updated “SAE” data 
collection tool/“Liver 
Event” documentsb

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Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
ALT≥5×ULN that 
persists ≥2 weeks 
24 hoursa
Liver Event eCRFb
24 hours 
Updated Liver Event 
eCRFb
ALT ≥8×ULN 
24 hoursa
Liver Event eCRFb
24 hours 
Updated Liver Event 
eCRFb
ALT ≥3×ULN  (if 
baseline ALT is <ULN) 
or ALT ≥3 fold 
increase from baseline 
value (if
baseline ALT >ULN) 
with appearance or 
worsening of 
symptoms of hepatitis 
or hypersensitivity
24 hoursa
Liver Event eCRFb
24 hours
Updated Liver Event 
eCRFb
a. The Medical Monitor must be contacted at onset of liver chemistry elevations to discuss participant safety.
b. Liver event documents (i.e., “Liver Event eCRF” and updates, “Liver Imaging eCRF” and/or “Liver Biopsy eCRF”, 
as applicable) should be completed as soon as possible.
12.8.7.
Reporting COVID-19 AEs and SAEs
Refer to Section 12.12.2.2 (Appendix 12 COVID-19 Guidance) for guidance on the 
reporting of COVID-19 specific AEs and SAEs.

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12.9.
Appendix 9: Toxicity Management
Adverse events that occur during the trial should be evaluated by the investigator and 
graded according to the DAIDS toxicity scales (see Appendix 7). Additional information 
regarding detecting, documenting and reporting AEs and SAEs are available in Section 
9.3.1.
Study drug may be interrupted at the discretion of the investigator and according to the 
severity of the AE. If one or more ART medication is held due to toxicity or AEs, all 
ART medications should be held to reduce the risk of development of resistance taking 
into account the length of the planned interruptions and the PK half-life of each ART of 
the regimen, in order to minimise the risk of development of resistance.
No toxicity-related dose reductions of study drugs will be allowed.  Study drugs should 
be restarted as soon as medically appropriate; in general, this should be no longer than 
4 weeks after interruption (unless Grade 3 or 4 toxicities persist).  Decisions regarding 
sequential reintroduction of study drugs or temporary interruption of one but not all drugs 
within the ART regimen should be made with the understanding that these changes may 
result in incomplete viral suppression and selection of resistant virus.  Guidance is 
provided below on participant management and study drug interruptions based on the 
severity of the AE for specific toxicities.  All changes in study drug must be accurately 
recorded in the participant’s eCRF.
[For general guidelines on the management of specific toxicities [including liver 
chemistry stopping and follow up criteria, restarting study drug, decline in renal function, 
allergic reaction, rash, hypertriglyceridaemia/hypercholesterolaemia and CPK elevation]  
that are considered to be related or possibly related to study treatment see Section 12.9.1
Specific Toxicities/Adverse Event Management.
Grade 1 or Grade 2 Toxicity/Adverse Event
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study 
treatment at the discretion of the investigator.  Participants who choose to withdraw from 
the study due to a Grade 1 or 2 AE should have study withdrawal and follow-up 
evaluations completed.
Grade 3 Toxicity/Adverse Event
Participants who develop a Grade 3 AE or toxicity should be managed as follows: 
If the investigator has compelling evidence that the Grade 3 AE or toxicity has not been 
caused by study treatment, dosing may continue after discussion with the Medical 
Monitor.
Participants who develop a Grade 3 AE or toxicity that the investigator considers related 
or possibly related to the study drugs should have study treatment withheld and be 
rechecked each week until the AE returns to Grade 2.  Once the AE is Grade ≤2, study 
treatment may be restarted. 

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Should the same Grade 3 AE recur within 28 days in the same participant, study 
treatment should be permanently discontinued and the participant withdrawn from study.  
Participants experiencing Grade 3 AEs requiring permanent discontinuation of study 
treatment should be followed weekly until resolution of the AE and have withdrawal 
study evaluations completed.  A Follow-up visit should be performed 4 weeks after the 
last dose of study drugs.
Participants with asymptomatic Grade 3 laboratory abnormalities should be investigated 
for all potential non-drug related causes, and, following discussion with the Medical 
Monitor, may continue study drug if the investigator has compelling evidence that the 
toxicity is not related to study treatment.
Exceptions are noted for lipid abnormalities in Section 12.9.1.6 and rash in Section 
12.9.1.5
Grade 4 Toxicity/Adverse Event
Participants who develop a Grade 4 AE or toxicity should have study treatment 
discontinued.  However, if the investigator has compelling evidence that the AE is not 
causally related to the study drugs, dosing may continue after discussion with and assent 
from the Medical Monitor.  Participants should be rechecked each week until the AE 
returns to Grade 2.
Participants experiencing Grade 4 AEs requiring permanent discontinuation of study 
treatment should be followed weekly until resolution of the AE and encouraged to 
complete the withdrawal and follow-up study evaluations as noted above.
Participants with asymptomatic Grade 4 laboratory abnormalities should be investigated 
for all potential non-drug related causes, and, following discussion with the Medical 
Monitor, may continue therapy if the investigator has compelling evidence that the 
toxicity is not related to study treatment.  Exceptions are noted for lipid abnormalities in 
Section 12.9.1.6.  An in-clinic Follow-up visit will be conducted approximately 4 weeks 
after the last dose of study medication for participants with ongoing AEs, and SAEs and 
also any laboratory abnormalities that are considered to be AEs or potentially harmful to 
the participant, at the last on-study visit.
12.9.1.
Specific Toxicities/Adverse Event Management
General guidelines for the management of specific toxicities that are considered to 
be related or possibly related to study treatment are provided below. 
Participants who permanently discontinue study treatment for reasons of toxicity should 
be followed weekly until resolution of the AE and encouraged to complete the 
withdrawal and follow-up study evaluations as noted in Section 12.9.
12.9.1.1.
Liver Chemistry Stopping and Follow-up Criteria
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event aetiology during administration of study drug and the 

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follow-up period. For a complete listing of stopping and follow-up criteria refer to
Section 8.1.2.
12.9.1.2.
Restarting Study Drug
Refer to Section 8.1.4 and Section 12.5 Appendix 5 for details on drug restart following 
transient resolving liver events not related to study treatment.
12.9.1.3.
Decline in Renal Function
Note: DTG can inhibit the tubular secretion of creatinine and can therefore be associated 
with a slight increase in serum creatinine and apparent decrease in the estimated 
glomerular filtration rate (generally by 10% or less). This typically occurs within the first 
4 weeks of treatment with DTG and remains stable thereafter and is not associated with 
renal damage or true decline in renal function. See below for advice on management of 
renal toxicity by DAIDS grading.
Note:  Utilize absolute creatinine or creatinine clearance value when determining the 
respective DAIDS severity bands.  
Serum creatinine and eGFR rates will be routinely monitored in this study. At each time 
point when serum creatinine testing is performed, the eGFR rate will be calculated using 
the bedside Schwartz formula: 
eGFR (mL/min/1.73 m2) = 0.413 * height (in cm) ÷ serum creatinine (in mg/dL)
Both the serum creatinine level and the eGFR rate will be graded for severity and 
assessed for change from baseline and clinical significance. When abnormal results are 
obtained, confounding factors and other non-study drug explanations (e.g., concomitant 
medications, concomitant illness, dehydration) should be considered and a nephrology 
consult may be obtained. 
Creatinine 
Participants who experience an increase to Grade 2 from a normal or Grade 1 serum 
creatinine level at baseline, or an increase to Grade 3 from a normal, Grade 1 or Grade 2 
creatinine level at baseline may continue study treatment but should undergo 
confirmatory testing within 2-4 weeks. Participants who develop a Grade 4 creatinine 
level should have study treatment temporarily held and have confirmatory testing within 
2 weeks. Serum creatinine testing should be repeated and consideration should also be 
given to performing a urinalysis assessing urine albumin:creatinine and urine 
protein:creatinine ratios and if the elevation is confirmed, the study Medical Monitor 
should be consulted regarding further follow-up and management. 
For a confirmed Grade 4 creatinine, study drug should be permanently 
discontinued. 

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eGFR
Participants who experience an increase from a normal, Grade 1, or Grade 2 eGFR at 
baseline to Grade 3 eGFR rate may continue study treatment but should undergo 
confirmatory testing within 2-4 weeks. Participants who develop a Grade 4 eGFR should 
have study treatment temporarily held and have confirmatory testing within 2 weeks. 
Other signs of renal toxicity should be sought and any alternative cause of renal 
impairment should be explored and treated appropriately. Consideration should also be 
given to assessing cystatin-C and performing a urinalysis assessing urine 
albumin:creatinine and urine protein:creatinine ratios.
If the increase to Grade 3 eGFR and/or a Grade 3 creatinine is confirmed, study drug 
should be temporarily held and the study Medical Monitor should be consulted regarding 
further follow-up and management.
Consideration should be given to a nephrology consultation, and the case discussed by 
the study team to determine benefit risk balance of continuing with study drug. 
For a confirmed Grade 4 eGFR, study drug should be permanently discontinued.
Participants requiring permanent discontinuation of study drug should be followed 
weekly until resolution and have withdrawal study evaluations completed. A follow-up 
visit should be performed 4 weeks after the last dose of study drugs.
12.9.1.4.
Allergic reaction
Participants may continue study drug for Grade 1 or 2 allergic reactions at the discretion 
of the Investigator.  The participant 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. 
Participants with Grade ≥3 allergic reactions that are considered to be possibly or 
probably related to the study drug should permanently discontinue study treatment and 
the participant should be withdrawn from the study.  Participants should be treated as 
clinically appropriate and followed until resolution of the AE.
12.9.1.5.
Rash
Mild to moderate rash is an expected adverse reaction for DTG-containing ART.  
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.  
No instances of serious skin reaction, including SJS, TEN and erythema multiforme, have 
been reported for DTG in clinical trials.  For further characterisation of HSR and rash 
observed with DTG-containing ART, please see the current version of the IB 
[GlaxoSmithKline Document Number RM2007/00683/12].
Participants with an isolated Grade 1 rash may continue study drug at the Investigator’s 
discretion.  The participant should be advised to contact the Investigator immediately if 

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there is any worsening of the rash, if any systemic signs or symptoms appear, or if 
mucosal involvement develops.
Participants may continue study drug for an isolated Grade 2 rash.  However, study drug 
(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 participant 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 mucosal 
involvement develops.
Participants should permanently discontinue study drug [and all other concurrent 
medication(s) suspected in the Investigators causality assessment] for an isolated Grade 3 
or 4 rash, except where the aetiology of the rash has been definitively diagnosed as NOT 
attributable to study drug (see below), and the participant should be withdrawn from the 
study.  Participants should be treated as clinically appropriate and followed until 
resolution of the AE.  Every effort should be made to collect as much information as 
possible about the evolution of the event and any relationship with potentially related 
medical events (e.g. viral infection) or start of concomitant medication.
The rash and any associated symptoms should be reported as adverse events and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS toxicity 
gradings, Section 12.7).
However, if the aetiology of the rash has been definitively diagnosed as being unrelated 
to study drug and due to a specific medical event or a concomitant infection or a 
concomitant non-study medication, routine management should be performed and 
documentation of the diagnosis provided. In this situation, the study drug should be 
continued. 
12.9.1.6.
Hypertriglyceridemia/Hypercholesterolemia
Samples for lipid measurements must be obtained in a fasted state according to the 
Schedule of Activities Table (Section 2).  Participants who experience asymptomatic 
triglyceride or cholesterol elevations may continue to receive study drug.
12.9.1.7.
Creatine Phosphokinase (CPK) Elevation
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2 to 4 
weeks to ensure the result is transient or due to exercise and will not require a change in 
study treatment.  A history regarding use of drugs known to cause increase of CPK (such 
as statins), physical activity or exercise preceding the CPK evaluation should be obtained.  
Grade 4 elevations in CPK should have a repeat assessment after the participant has 
abstained from exercise for >24 hours.  For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the study drugs, study treatment should be 
discontinued and the participant withdrawn from the study.

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12.10.
Appendix 10: Modified List of Highly Effective Methods for 
Avoiding Pregnancy and Collection of Pregnancy 
Information
12.10.1.
Modified List of Highly Effective Methods for Avoiding Pregnancy 
in Females of Reproductive Potential (FRP)
The list does not apply to FRP with same sex partners or for participants who are and will 
continue to be abstinent from penile-vaginal intercourse on a long term and persistent 
basis, when this is their preferred and usual lifestyle. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception.
FRP are eligible to participate if they agree to use a highly effective method of 
contraception consistently and correctly as described
1.
Contraceptive subdermal implant
2.
Intrauterine device or intrauterine system
3.
Combined estrogen and progestogen oral contraceptive [Hatcher, 2011]
4.
Injectable progestogen [Hatcher, 2011]
5.
Contraceptive vaginal ring [Hatcher, 2011]
6.
Percutaneous contraceptive patches [Hatcher, 2011]
7.
Male partner sterilisation with documentation of azoospermia prior to the female 
participant's entry into the study, and this male is the sole partner for that participant 
[Hatcher, 2011].The documentation on male sterility can come from the site 
personnel’s review of participant’s medical records, medical examination, and/or 
semen analysis, or medical history interview provided by her or her partner.
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The investigator is responsible for 
ensuring that participants understand how to properly use these methods of contraception.
12.10.2.
Collection of Pregnancy Information

Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study.

Information will be recorded on the appropriate form and submitted to ViiV 
Healthcare/GSK within 24 hours of learning of a participant's pregnancy.

Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to ViiV Healthcare/GSK/PPD Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. GSK’s 
central safety department also will forward this information to the Antiretroviral 
Pregnancy Registry. The international registry is jointly sponsored by manufacturers 

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or licensees of antiretroviral products. Additional information and a list of 
participating manufacturers/licensees are available from http://www.apregistry.com/.

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.

A spontaneous abortion is always considered to be an SAE and will be reported as 
such.

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to ViiV 
Healthcare/GSK as described in Section 12.8.6. While the investigator is not 
obligated to actively seek this information in former study participants, he or she 
may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant (intrauterine) while participating in 
this study must be withdrawn from the study and must immediately discontinue 
study drug.
Reference
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007:28.
Hatcher RA, Trussell J, Nelson AL, et al, editors. Contraceptive Technology. 
20th edition. Atlanta, Georgia: Ardent Media, Inc., 2011: 50. Table 3-2.

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12.11.
Appendix 11: Decision Flow- Screening Tests for Hepatitis B 
Virus Serology, Interpretation and Action

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12.12.
Appendix 12: COVID-19 Guidance
12.12.1.
COVID -19 Experimental Agents
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study medical monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate.
12.12.2.
COVID-19 Specific Data Capture
12.12.2.1. Capturing COVID-19 Specific Protocol Deviations
Your PPD Monitor will provide specific guidance on capturing protocol deviations as a 
result of COVID-19, if needed.  
12.12.2.2.
Capturing COVID-19 Specific AEs and SAEs
It is important for the study team to describe COVID-19 related adverse events/serious 
adverse events and their impact on study data and outcomes. Standardization of case 
definitions will facilitate future data analysis. 
Please use the following guidance: 
1.
AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual study 
procedures and timelines. 
2.
When an in-person clinic visit is not possible, please conduct a remote telehealth 
visit to assess for, and document any AEs/SAEs.
3.
Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released 20 March 2020, represents a time point for 
standardized collection. We recognize definitions are likely to continue to evolve. 
When reporting both serious and non- serious adverse events (related to 
COVID-19 infection, investigators should use the following Verbatim terms: 
a.
Suspected COVID-19 infection; or 
b. Probable COVID-19 infection; or 
c.
Confirmed COVID-19 infection. 
4.
Sites should contact the study Medical Monitor for questions related to definitions 
and reporting, and decisions around impact to study drug continuation. 
5.
A new COVID-19 infection Case Report Form has been added to the eCRF to 
collect additional details about the reported COVID-19 AE or SAE data. It is 
important to collect the correct information from each participant reporting a 
COVID-19 AE or SAE. Therefore, please use the CRF templates to collect this 
information.

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WHO Case Definition – 20 March 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)): 
Suspected case: 
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset; 
OR 
B.
A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset; 
OR 
C. A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation. 
Probable case: 
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(Inconclusive being the result of the test reported by the laboratory). 
OR 
B.
A suspect case for whom testing could not be performed for any reason. 
Confirmed case: 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms. 
Covid-19 Contact:
A contact is a person who experienced any one of the following exposures during the 
2 days before and the 14 days after the onset of symptoms of a probable or confirmed 
case: 
1.
Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes; 
2.
Direct physical contact with a probable or confirmed case; 
3.
Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR 

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4.
Other situations as indicated by local risk assessments. 
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before, through the 14 days after the date on which the sample was taken which led to 
confirmation.

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12.13.
Appendix 13: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
Amendment 1, 13-Jun-2018
Overall Rationale for the Amendment:
In one ongoing birth outcome surveillance study in Botswana, early results from an 
unplanned interim analysis show that 4/426 (0.9%) of women who were taking DTG 
when they became pregnant had babies with neural tube defects compared to a 
background rate of 0.1%. 
Risk of neural tube defect was added to the Benefit/Risk Assessment for this study. 
The protocol was updated to reinforce the importance of pregnancy avoidance and 
contraception requirements. 
A correction to the timing of intensive PK sample collection was made within the 
Schedule of Activities footnote.

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Section # and Name
Description of Change
Brief Rationale
Section 2, Schedule of 
Activities: Sample for 
pharmacokinetic 
analysis (intensive 
serial collection-
subset of participants
Footnote corrected to remove 
sample collection timepoints at 
8 and 12 hours and insert a 
sample collection timepoint at 
10 hours.
Clarification of collection timepoints 
for intensive PK sampling.
Section 2, Schedule of 
Activities: Pregnancy 
Testing
Footnote added for 
Investigators and/or site staff to 
remind females of reproductive 
potential of the need to avoid 
pregnancy while in study and 
adhere to the study’s 
contraception requirements.
Updated to reinforce the importance 
of pregnancy avoidance and 
contraception requirements. 
Section 3.3.1, Risk 
Assessment
DTG: Addition of neural tube 
defects as a potential risk of 
clinical significance during use 
in pregnancy. Updated 
mitigation strategy.
In one ongoing birth outcome 
surveillance study in Botswana, early 
results from an unplanned interim 
analysis show that 4/426 (0.9%) of 
women who were taking DTG when 
they became pregnant had babies 
with neural tube defects compared to
a background rate of 0.1%. 
Risk of neural tube defect was added 
to the Benefit/Risk Assessment for 
this study.
Section 6.1, Inclusion 
Criteria
Change in the timeframe for 
use of acceptable methods of 
birth control by females of 
reproductive potential (FRP) to 
require use 28 days prior to the 
first dose of study medication 
until the last dose of study 
medication and completion of 
the Follow-up visit (4 weeks 
after the last dose).
Original timeframe required use 
prior to the first dose of study 
medication and up to 2 weeks 
after the last dose of study 
medication.
Refined to allow time for start of 
hormonal methods of birth control 
and reduce the likelihood of 
pregnancy in females of reproductive 
potential during exposure to 
dolutegravir.

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Section # and Name
Description of Change
Brief Rationale
Section 8.2, 
Withdrawal form 
Study and Stopping 
Criteria
Addition of a reminder noting 
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 
methods, should also be 
withdrawn from the study.
Updated to reinforce the importance 
of pregnancy avoidance and 
contraception requirements. 
Section 11, 
References
DTG Investigator’s Brochure 
version 11, supplements 01 
and 02 were added to 
reference list.
DTG Investigator’s Brochure (IB) 
version update.
Section 12.10.1, 
Appendix 10, Modified 
List of Highly Effective 
Methods for Avoiding 
Pregnancy in Females 
of Reproductive 
Potential (FRP)
Removal of male condom 
combined with vaginal 
spermicide (foam, gel, film, 
cream, or suppository) from the 
list of highly effective methods 
for avoiding pregnancy.
List of acceptable highly effective 
methods of contraception was refined 
to reduce the likelihood of pregnancy 
in females of reproductive potential 
during exposure to dolutegravir.

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Amendment 2, 13-Nov-2019
Overall Rationale for the Amendment:
A Continuation Phase is incorporated to enable post study drug provision for eligible 
participants who may benefit from continued treatment. If required by local regulations, 
study participants who have successfully completed both the Treatment Phase through 
Week 48 and the Extension Phase through Week 144 will be given the opportunity to 
continue to receive DTG/3TC once daily in the Continuation Phase, regardless of age, 
until: DTG and 3TC are both locally approved for use as part of a dual regimen, and the 
single entities of DTG and 3TC are available to patients (e.g. through public health 
services), or the DTG/3TC FDC tablet is locally approved and available (e.g. 
commercially or through public health services), or the participant no longer derives 
clinical benefit or meets a protocol-defined reason for discontinuation. Analyses may be 
conducted as necessary after Week 144 to support regulatory submissions and 
publications. 
A planned 96-week secondary analysis is incorporated to assess long-term durability of 
response and evaluate potential risk of resistance associated substitutions. 
A change in weight entry criterion, from 40 kg and above to 25 kg and above, is 
incorporated.  This change is supported by current dosing recommendations for 3TC in 
pediatric patients weighing 25 kg and above (300 mg daily, taken as 150 mg BID or 
300 mg QD, as per EPIVIR product label) and recent pharmacokinetic data from the 
ODYSSEY study which supports use of DTG at the adult dose (50 mg) in children 
weighing 25 kg and above. 
Section # and 
Name
Description of Change
Brief Rationale
Protocol Title 
Section 1 Summary
•
Addition of compound number for 
fixed dose combination DTG/3TC
•
Change in adolescent weight cut 
off from 40 kg to 25 kg.
•
Compound numbers for 
single entities (DTG and 
3TC) were included within 
the original Protocol Title 
page. Compound number for 
the DTG/3TC Fixed Dose 
Combination (FDC) used in 
this study was added for 
clarity.
•
Current dosing 
recommendations for 3TC in 
paediatric patients weighing 
≥25 kg is 300 mg daily and 
can be taken as 150 mg BID 
or 300 mg QD [EPIVIR PI]; 
Recent pharmacokinetic 
data from the ODYSSEY 
study supports use of DTG 

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Section # and 
Name
Description of Change
Brief Rationale
at the adult dose (50 mg) in 
children weighing ≥25 kg.
Medical 
Monitor/SAE 
Contact information
•
Shifted PPD Medical Monitor and 
SAE reporting information from 
footnote to body of table.
•
PPD Medical Monitor and 
Safety Hotline are first line 
points of contact for sites. 
Information embedded within 
table to facilitate reference.
Section 2 Schedule 
of Activities
•
Added Continuation Phase and 
applicable Continuation Phase 
assessments after the Week 144 
Visit.
•
Added collection of fasting lipids, 
glucose and HbA1c at the time of 
withdrawal from the study if the 
withdrawal visit occurred at 
weeks 48, 96 or 144.
•
Added note stating CSSRS 
participant level reports should be 
reviewed, signed by Investigator 
or Sub-Investigator and files in 
site source with actions taken for 
positive findings clearly 
documented.
•
Table was reformatted for clarity. 
Footnotes were incorporated 
within each applicable 
assessment line item. 
Assessment timepoint markings 
(‘X’) were reformatted to reflect 
actual assessment timepoint 
(such as SC for screening visit, B 
for baseline visit, etc.).
•
A Continuation Phase was 
added to enable post study 
drug provision for eligible 
participants who may benefit 
from continued treatment. 
•
Serum lipid and blood 
glucose levels may increase 
during antiretroviral therapy. 
Collection of fasting lipids, 
glucose and HbA1c at the 
time of withdrawal from the 
study at weeks 48, 96 or 144 
was added to align with data 
collection in the adult 
DOVATO studies (GEMINI-1 
and GEMINI-2).
•
Investigator review of 
CSSRS reports, and 
documentation of the review 
and any action taken, is 
important.  A reminder 
regarding required 
documentation at the site 
was added to the table.
•
Schedule of Activities table 
was reformatted to facilitate 
reference.
Section 3 
Introduction
•
Added 48-week and 96-week 
results from GEMINI-1 and 
GEMINI-2 studies.
•
Referenced DOVATO approval 
•
GEMINI-1 and GEMINI-2 48-
week and 96-week study 
results were incorporated for 
completeness.  
•
Reference to recent 
DOVATO approvals added 
for completeness. 

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Section 3.1 
Background 
•
Added 48-week and 96-week 
results from GEMINI-1 and 
GEMINI-2 studies.
•
GEMINI-1 and GEMINI-2 48-
week and 96-week study 
results were incorporated for 
completeness.  
Section 3.3 
Benefit:Risk 
Assessment
•
Added DOVATO product label as 
reference.
•
Reference added for 
completeness.  
Section 3.3.1 
Benefit:Risk 
Assessment- Neural 
Tube Defect
•
Updated risk of neural tube 
defect to reflect current data 
(change in rate from 0.9% to 
0.3%).  The following update was 
provided: 
In a birth outcome surveillance 
study in Botswana there have 
been 5 cases of neural tube 
defects reported in 1,683 
deliveries (0.3%) to mothers 
taking dolutegravir-containing 
regimens from the time of 
conception, compared with 15 
cases in 14,792 deliveries (0.1%) 
to mothers taking non-
dolutegravir-containing regimens 
from the time of conception. 
In the same study, one out of 
3,840 deliveries (0.03%) to 
mothers who started dolutegravir 
during pregnancy had a neural 
tube defect, compared with three 
out of 5,952 deliveries (0.05%) to 
mothers who started non-
dolutegravir-containing regimens 
during pregnancy.
•
Recent data from 
surveillance study in 
Botswana added for 
completeness.
Section 3.3.1 Risk 
Assessment
Section 7.9.2 
Prohibited 
Medications and 
Non-Drug 
Therapies
•
Addition of fampridine (also 
known as dalfampridine) to the 
list of prohibited medications.
•
Fampridine (also known as 
dalfampridine), is a substrate 
of organic cation transporter 
2 (OCT2) with a narrow 
therapeutic window, similar 
to dofetilide, that should not 
be administered concurrently 
with the DTG containing 

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products due to the potential 
risk of seizures.
Section 5 Study 
Design Section 5.3 
Participant and 
Study Completion
•
Noted that a participant will be 
considered to have completed 
the Continuation Phase after 
completion of the End of 
Continuation Phase Visit.
•
Updated Study Schematic to 
include Continuation Phase and 
planned 96-week secondary 
analysis.
•
An End of Continuation 
Phase Visit will be 
completed for participants 
transitioning to approved 
and locally available supply.
•
A planned 96-week 
secondary analysis was 
incorporated to assess long-
term durability of response 
and evaluate potential risk of 
resistance associated 
substitutions.
Section 5.5 Dose 
Justification
•
Added reference to DOVATO 
approvals
•
Added rationale for modification 
of weight entry criterion (change 
from 40 kg to 25 kg)
•
Reference to recent 
DOVATO approvals added 
for completeness.
•
Current dosing 
recommendations for 3TC in 
paediatric patients weighing 
≥25 kg is 300 mg daily and 
can be taken as 150 mg BID 
or 300 mg QD [EPIVIR PI]; 
Recent pharmacokinetic 
data from the ODYSSEY 
study supports use of DTG 
at the adult dose (50 mg) in 
children weighing ≥25 kg.
Section 6.1 
Inclusion Criteria
•
Inclusion #2 Change in weight 
entry criterion from ≥40 kg to 
≥25 kg.
•
Inclusion #4- Added inclusion of 
PEP/PrEP dose >6 months from 
HIV diagnosis or there is 
documented HIV seronegativity 
at least 2 months after the last 
prophylactic dose and prior to the 
date of HIV diagnosis.
•
Inclusion #2: Current dosing 
recommendations for 3TC in 
paediatric patients weighing 
≥25 kg is 300 mg daily and 
can be taken as 150 mg BID 
or 300 mg QD [EPIVIR PI]; 
Recent pharmacokinetic 
data from the ODYSSEY 
study supports use of DTG 
at the adult dose (50 mg) in 
children weighing ≥25 kg.
•
Inclusion #4- PEP/PrEP 
guidance added for 
completeness.

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Section 6.2 
Exclusion Criteria
•
Exclusion #7- Untreated syphilis 
infection (positive rapid plasma 
reagin [RPR] at Screening 
without clear documentation of 
treatment) is exclusionary. The 
original criterion required 
participants completed syphilis 
treatment at least 14 days prior to 
screening. The timeframe 
required for completion of syphilis 
treatment prior to screening was 
modified from ‘at least 14 days’ to 
‘at least 24 hours’.
•
Exclusion #2- Removed WHO 
Stage 3 exclusion as follows: Any 
evidence of an active Centers for 
Disease Control and Prevention 
(CDC) Stage3 and/or Category C 
or WHO Stage 3 or 4 disease 
(Appendix 6, Section 12.6), 
except cutaneous Kaposi’s 
sarcoma not requiring systemic 
therapy and historical or current 
CD4 cell counts less than 200 
cells/mm3 or CD4% <15%.
•
Exclusion #21- Addition –
exclusion of children who are 
wards of the state or government.
•
Exclusion #7: Patients with 
active syphilis, untreated or 
partially treated, may have 
or develop adverse events 
as part of their syphilitic 
disease, which may be 
confused with a potential IP 
effect. Thus, completion of 
syphilis treatment prior to 
initiation of IP is preferred. 
Adverse reactions to syphilis 
treatment, such as Jarisch-
Herxheimer reaction, 
typically occur within 24 
hours after completion of 
treatment [Butler, 2017; 
Yang, 2010]. The required 
timeframe for completion of 
syphilis treatment prior to 
Day 1 of the study was 
reduced to at least 24 hours. 
This change accounts for the 
timeframe in which adverse 
reactions may occur, while 
mitigating risk for delay in 
assessing eligibility and 
patient access to study 
treatment.   
•
Exclusion #2: WHO Stage 3 
was removed as exclusion 
as it is largely equivalent to 
CDC Stage 2, which is not 
exclusionary, and WHO 
Stage 4 is most similar to 
CDC Stage 3.
•
Exclusion #21: As per ViiV 
Healthcare policy, Children 
who are wards of state 
(children in care) should not 
be enrolled in this study.
Section 7.10 
Treatment after the 
End of Study 
•
Addition of Continuation Phase.
•
Addition of End of Continuation 
Phase Visit
•
A Continuation Phase was 
added to enable post study 
drug provision for eligible 

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participants who may benefit 
from continued treatment. 
•
The purpose of the End of 
Continuation Phase Visit is 
to document participant 
transition to locally approved 
and available DTG+3TC.
Section 9.6
Pharmacokinetic
•
Added sub section 9.6.1.2 
Collection of Ctrough samples-
All Participants
•
Added sub heading for 
collection of Ctrough 
samples for clarity
Section 9.6.1.1 
Collection of Sparse 
PK samples – All 
Participants 
•
Added footnote reminder -
participants are to complete a 
dosing diary card for 3 days prior 
to PK sampling Visits.
•
Completed Dosing Diary 
Cards will be collected for 
Ctrough, sparse and 
intensive PK visits.
Section 9.6.2
Important 
Information on 
collection of PK
samples
•
Added Sub section 9.6.2.1. for 
Timing of Sparse PK Samples 
and Dosing Diary Cards
•
Added Sub section 9.6.2.2. and 
clarification noting dosing diary 
cards should be collected 3 days 
prior to scheduled Ctrough, 
sparse or intensive PK clinic 
visits.
•
Sub heading was added to 
facilitate reference within the 
Table of Contents. 
•
Completed Dosing Diary 
Cards will be collected for 
Ctrough, sparse and 
intensive PK visits.
Section 10.3.1
Efficacy Analyses
•
Added details that analyses for 
Weeks 96 and 144 will be 
provided in RAP
•
For better clarity
Section 10.3.5 
Secondary 
Analyses
•
A planned Week 96 secondary 
analysis is added. At least 3 
analyses will be conducted to 
evaluate the primary and 
secondary objectives (at Weeks 
48,96 and 144). Further data cuts 
and analyses may be conducted 
as necessary after Week 144 to 
support regulatory submissions 
and publications.
•
Timing and triggers for 
Independent data monitoring 
committee (IDMC) data looks and 
meetings were added.
•
A planned Week 96 
secondary analysis was 
incorporated to assess long-
term durability of response 
and evaluate potential risk of 
resistance associated 
substitutions 
•
Clarification incorporated to 
note three planned analyses 
timepoints and potential for 
further data cuts and 
analyses as necessary to 
support regulatory 
submissions and 
publications.

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Section # and 
Name
Description of Change
Brief Rationale
•
Timings and triggers for 
IDMC data looks and 
meetings were added for 
completeness and 
transparency.
Section 11 
References
•
References updated
•
Updated references to align 
with amendment 
modifications for 
completeness.
Section 12.1 
(Appendix 1)
Abbreviations and 
Trademark 
Information 
•
DOVATO added to ViiV 
Healthcare group of companies 
list of trademarks.
•
Updated with DOVATO 
trademark for completeness.
Section 12.11 
(Appendix 11)
Decision Flow-
Screening Tests for 
Hepatitis B Virus 
Serology, 
Interpretation and 
Action
•
A decision flow chart, to assist in 
the interpretation of hepatitis B 
virus serology results, is added 
for reference.
•
Added for reference and 
clarity.
Throughout
•
Corrected inconsistencies, links 
and typos, and updated 
abbreviations
•
To improve quality of the 
protocol