Open-label Access to Dolutegravir for HIV-1 Infected Children and Adolescents Completing IMPAACT Studies P1093 and P2019
Phase: PHASE3
Conditions: HIV Infections
Sponsor: ViiV Healthcare

Protocol Amendment 05
Study ID:  205858
Official Title of Study: Open-label access to dolutegravir for HIV-1 infected 
children and adolescents completing IMPAACT Studies P1093 and P2019.
NCT number: NCT03016533
Date of Document: 21-Jun-2022

TMF-14008177 
CONFIDENTIAL 
The ViiV Healthcare group of companies 
205858 
Protocol Amendment 5 
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TITLE PAGE 
Protocol Title:  Open-label access to dolutegravir for HIV-1 infected children and 
adolescents completing IMPAACT Studies P1093 and P2019. 
Protocol Number:  205858 / Amendment 05 
Compound 
Numbers: 
GSK1349572 and GSK2619619 
Study Phase: 3B 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford, Middlesex, TW8 9GS, United Kingdom 
Telephone: +44 (0)20 8 380 6200 
US IND Sponsor Legal Registered Address: 
ViiV Healthcare Company 
Five Moore Drive 
P.O. 13398 
Research Triangle Park, NC 27709-3398, USA 
Telephone: + 1 919 438 2100 
In some countries, local law requires that the Clinical Trial sponsor is a local company 
legal entity.  In these instances, the appropriate company to be identified as sponsor must 
be agreed with the global ViiV Healthcare clinical team and signed off by the VP, Global 
Medical Strategy. 
This study is sponsored by ViiV Healthcare. GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study. 
Regulatory Agency Identifying Number(s):  Tivicay US IND# 075382; Triumeq US 
IND# 114820; EudraCT# 2011-001646-16  
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual (SRM). 
Sponsor Signatory: 
Sherene Shakib Min, MD, MPH 
Vice President, Head of Clinical Development, 
ViiV Healthcare 
Approval Date: 06 Jun 2022 
Copyright 2022 ViiV Healthcare and the GlaxoSmithKline group of companies.  All 
rights reserved.  Unauthorised copying or use of this information is prohibited 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 05 
06 Jun 2022 
TMF-14008177 
Amendment 04 
10-December-2020
2016N282439_04 
Amendment 03 
27-June-2019
2016N282439_03 
Amendment 02 
29-June-2018
2016N282439_02 
Amendment 01 
26-September-2016
2016N282439_01 
Original Protocol 
23-August-2016
2016N282439_00 
Amendment 05 – 06 Jun 2022 
Overall Rationale for the Amendment: 
Below mentioned are the changes with rationale incorporated in Amendment 05: 
Exclusion criteria were clarified to more closely align with the penultimate and end of 
study visit period and assessments in the parent studies.  
Device deficiency reporting requirements were removed as the study is outside the scope 
of United States Food and Drug Administration (US FDA) 21 CFR 4 Subpart B 
(Regulation of Combination Products).  
The DTG 50 mg film coated tablet was approved for use in children weighing 20 kg and 
above in the Unites States, European Union and many other countries. Therefore, the 
DTG film coated tablet weight based dosing table in the appendix was removed and 
replaced with updated dosing instructions for participants weighing 20 kg and above. 
DTG dispersible tablets may be utilized in patients weighing 3 kg and above.   
In addition, the ABC/DTG/3TC (600 mg/50 mg/ 300 mg) immediate release tablet 
received approval for use in the United States for patients weighing 25 kg and above in 
March 2022, and ABC/DTG/3TC (60 mg/5 mg/30 mg) dispersible tablet weight-based 
dosing was approved for use in patients weighing at least 10 kg in the United States at the 
same time. Additional marketing applications for the ABC/DTG/3TC dispersible tablet 
and immediate release tablets for pediatric patients are under review by the EMA. 
Other changes include minor updates to protocol text with regards to latest template and 
additions made throughout for protocol text clarity. 
Section # 
and Name 
Description of Change 
Brief Rationale 
2. Introduction
Added European Medicines Agency 
(EMA) regulatory approval details. 
Updated as per available 
details.  
4.6.1 Risk 
Updated footnote associated with 
Footnote updated to provide 

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Section # 
and Name 
Description of Change 
Brief Rationale 
Assessment for DTG 
monitoring SAEs and AEs leading to 
treatment discontinuation.  
clarity. 
5.2. Exclusion 
Criteria (Exclusion 
Criterion 3) 
4.6.2 Risk 
Assessment for 
ABC/DTG/3TC 
Before: Known ≥Grade 3 laboratory 
toxicities within 30 days prior to study 
entry (e.g. neutrophil count, hemoglobin, 
platelets, aspartate aminotransferase 
(AST), ALT, lipase, serum creatinine and 
total bilirubin). Repeat testing is allowed 
for eligibility determination. NOTE:  
≥Grade 3 total bilirubin is allowable, if 
the subject is on ATV. 
NOTE: Subjects with laboratory 
abnormalities considered unrelated to IP 
may be allowed to enter the study. Thus, 
if the laboratory abnormality persists 
upon repeat testing, the subject may be 
considered for study entry after 
consultation and approval of the study 
team. 
Modified (in bold): Known ≥Grade 3 
laboratory toxicities (e.g. neutrophil 
count, hemoglobin, platelets, aspartate 
aminotransferase (AST), ALT, lipase, 
serum creatinine, eGFR and total 
bilirubin) would be considered 
exclusionary if identified at or after 
the penultimate parent study visit, 
prior to enrollment in the study. 
Repeat testing is allowed for eligibility 
determination. NOTE:  ≥Grade 3 total 
bilirubin is allowable, if the subject is on 
ATV. 
NOTE: Subjects with laboratory 
abnormalities considered unrelated to IP 
may be allowed to enter the study. Thus, 
if the laboratory abnormality persists 
upon repeat testing, the subject may be 
considered for study entry after 
consultation and approval of the study 
team. An exception to this note is for 
participants with confirmed creatinine 
clearance of less than 30 mL/min in 
Timeframe clarified to more 
closely align with the 
penultimate and end of study 
visit period in the parent 
studies. 
Language was amended to 
maintain uniformity in protocol 
text of Section 4.6.2 as per 
updates made to Exclusion 
criteria 3. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
which DTG/ABC/3TC FDC should not 
be used. 
5.2 Exclusion Criteria 
(Exclusion Criteria 5) 
Before: ALT ≥5 times the ULN, OR ALT 
≥3xULN AND bilirubin ≥1.5x ULN (with 
>35% direct bilirubin) within 30 days
prior to study entry. Subjects with
moderate to severe hepatic impairment
(Class B or greater) as determined by
Child-Pugh classification should be
excluded.
Modified (in bold): Known ALT ≥5xULN, 
OR ALT ≥3xULN AND bilirubin ≥1.5x 
ULN (with >35% direct bilirubin) would 
be considered exclusionary if 
identified at or after the penultimate 
parent study visit, prior to enrollment 
in the study. Subjects with moderate to 
severe hepatic impairment (Class B or 
greater) as determined by Child-Pugh 
classification should be excluded. 
Timeframe clarified to more 
closely align with the 
penultimate and end of study 
visit period in the parent 
studies. 
5.2 Exclusion Criteria 
(Exclusion Criteria 6) 
Before: Subjects positive for hepatitis B 
virus in the parent study (hepatitis B 
virus surface antigen positive). 
After (in bold): Subjects positive for 
hepatitis B virus at any time prior to 
entry (hepatitis B virus surface antigen 
positive). 
Addition made for clarity with 
respect to parent study 
timeframe. 
5.2 Exclusion Criteria 
(Previous Exclusion 
Criteria 6) 
Deleted exclusion criteria 6 
The eGFR value of <60 is 
equivalent to DAIDS severity 3 
grading. As exclusion criteria 3 
rules out laboratory toxicities of 
grade ≥3, the previous eGFR 
exclusion criteria was removed 
and eGFR was added to the 
list of examples noted within 
exclusion criteria 3.  
A reminder was included within 
exclusion criteria 3 to note that 
ABC/DTG/3TC should not be 

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Section # 
and Name 
Description of Change 
Brief Rationale 
used in subjects with creatinine 
clearance of less than 30 
mL/min. 
6.9 Treatment after 
the End of the Study 
Provisions under which study drug will 
be made available to subjects has been 
incorporated. 
The duration of subject 
participation in the study will 
extend until age appropriate 
formulations of DTG or 
ABC/DTG/3TC receive local 
(by country) regulatory 
approval and are available 
commercially in those 
countries or other availability 
occurs from another source 
(e.g. government programs, 
aid programs, assistance 
programs, etc.). 
Table 7.1.1 Parent 
Studies: Penultimate 
Visit Assessments 
Addition made to P1093 laboratory 
evaluations assessment section for 
“Additional evaluations if clinically 
indicated”  
Updated to align with current 
P1093 protocol 
7.2 Time and Events 
Table 
Updated Table 2 for SAEs during 
screening visit. Footnote 5 was amended 
for clarifying SAEs related to study 
participation will be captured in e-CRF 
and rest of other SAEs if occurring will 
be captured in DAIDs sponsored parent 
studies. 
Updated for Clarity and to align 
with current protocol  
7.3 Screening Visit 
Addition made with respect to the 
activities to be conducted during 
screening visit.  
Note was amended to mention HIV-1 
RNA and pregnancy test results will be 
recorded in eCRF and source notes 
respectively.  
Details added for maintaining 
uniformity as per time and 
events table.  
Amended for providing 
distinction for recording 
requirements and location for 
HIV-1 RNA and pregnancy 
tests results.  
6.1.1 Medical 
Devices 
7.6.1.5  Medical 
Device Deficiencies 
Removed description of medical device 
deficiencies reporting activities.  
Where required, medical 
devices are locally sourced by 
study sites and not supplied by 
the sponsor in this study. It 
was therefore determined that 

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Section # 
and Name 
Description of Change 
Brief Rationale 
7.6.1.6 Time Period 
for Detecting Medical 
Device Deficiencies 
 7.6.1.7 Prompt 
reporting of Medical 
Device Deficiencies 
to the Sponsor    
12.8 Previous 
Appendix 8 
Reporting a Medical 
Device Deficiency 
this study is outside of the 
scope of the United States 
Food and Drug Administration 
(US FDA) 21 CFR 4 Subpart B 
(Regulation of Combination 
Products). Hence, Device 
Deficiency safety requirements 
are no longer reported.  
12.8.1 COVID-19 
Experimental Agents 
Added HIV-1 RNA collection 
requirements 
As vaccines may cause a 
temporary increase in the level 
of HIV-1 plasma RNA, 
recommendation was added 
that HIV-1 RNA collection 
should occur 2-4 weeks from 
COVID vaccination. 
2. Introduction and
6.5.1. DTG Film-
Coated Tablets
Section 12.2.1 
Tivicay DTG Film 
Coated Tablets 
Deleted text for 25 mg and 10 mg DTG 
film coated tablet. 
Added text for DTG 5 mg dispersible 
tablets for oral suspension. 
Deleted weight based dosing table from 
Appendix Section 12.2.1 Tivicay DTG 
film coated tablet. 
Added guidance for switching from 30 
mg DTG to 50 mg film coated tablet. 
The DTG 50 mg film coated 
tablet is approved for use in 
children weighing 20 kg and 
above. Therefore, weight 
based dosing table for Tivicay 
DTG film coated tablets has 
been removed from the 
appendix. A reminder was 
added to note that participants 
weighing 20 kg and above may 
transition to Tivicay DTG 50 
mg film coated tablets.  
Section 12.7.2 
Definition of SAE 
SAE definition 
Minor update as per template 
language was incorporated. 
SAE definition remains the 
same.  
12.7.5. Reporting of 
SAEs and AEs 
leading to 
discontinuation of IP 
Removed the Investigator requirement of 
marking the ‘reviewed’ box for confirming 
event causality in the eCRF page within 
Removal of repetitive step as 
an earlier section already 
describes that the Investigator 

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Section # 
and Name 
Description of Change 
Brief Rationale 
to GSK/ViiV 
Healthcare/PPD 
72 hours of submission. 
has to perform this check. 
Throughout 
Minor editorial and document formatting 
revisions 
Minor, therefore have not been 
summarized 

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MEDICAL MONITOR/SPONSOR INFORMATION PAGE 
Medical Monitor/Serious Adverse Event (SAE) Contact Information: 
Role 
Name 
Day Time Phone Number and 
Fax  
After-hours 
Phone/Cell/ 
Pager 
Number 
Site Address 
Medical 
Monitor/ 
SAE 
Contact 
PPD 
Safety 
Hotline 
(800) 201-8725, phone
(888) 488-9697, fax
(800) 201-
8725
PPD 
929 North Front 
Street 
Wilmington, NC 
28401 
This study is sponsored by ViiV Healthcare LLC. Pharmaceutical Product Development, 
LLC (PPD) will implement and manage all aspects of this study. The study is performed 
in compliance with PPD Standard Operating Procedures for all processes involved, 
including the archiving of essential documents.  

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INVESTIGATOR PROTOCOL AGREEMENT PAGE 
For protocol number 205858 
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment. 
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name: 
Investigator Address: 
Investigator Phone Number: 
Investigator Signature 
Date 

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TABLE OF CONTENTS 
PAGE 
1.
PROTOCOL SYNOPSIS FOR STUDY 205858 ...................................................... 14 
2.
INTRODUCTION .................................................................................................... 16 
2.1. 
Study Rationale .......................................................................................... 17 
2.2. 
Brief Background ........................................................................................ 17 
3.
OBJECTIVES AND ENDPOINTS ........................................................................... 19 
4.
STUDY DESIGN .................................................................................................... 19 
4.1. 
Overall Design ............................................................................................ 19 
4.2. 
Treatment Arms and Duration ..................................................................... 20 
4.2.1. 
DTG for subjects transitioning from P1093 ................................... 20 
4.2.2. 
ABC/DTG/3TC for subjects transitioning from P2019 ................... 20 
4.2.3. 
Weight based dose adjustments for all subjects........................... 21 
4.3. 
Type and Number of Subjects ..................................................................... 21 
4.4. 
Design Justification ..................................................................................... 21 
4.5. 
Dose Justification ........................................................................................ 21 
4.6. 
Benefit:Risk Assessment ............................................................................ 21 
4.6.1. 
Risk Assessment for DTG ............................................................ 22 
4.6.2. 
Risk Assessment for ABC/DTG/3TC ............................................ 25 
4.6.3. 
Benefit Assessment ..................................................................... 27 
4.6.4. 
Overall Benefit:Risk Conclusion ................................................... 28 
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA ............. 28 
5.1. 
Inclusion Criteria ......................................................................................... 29 
5.2. 
Exclusion Criteria ........................................................................................ 30 
5.3. 
Screening Failures ...................................................................................... 32 
5.4. 
Withdrawal/Stopping Criteria....................................................................... 32 
5.4.1. 
Criteria for Study Discontinuation ................................................. 32 
5.4.2. 
Criteria for IP Discontinuation ...................................................... 32 
5.4.3. 
Management of Renal Toxicity ..................................................... 33 
5.4.3.1. 
Creatinine ................................................................... 33 
5.4.3.2. 
eGFR.......................................................................... 34 
5.4.4. 
Liver Chemistry Stopping Criteria ................................................ 34 
5.4.5. 
Study Treatment Restart and Rechallenge .................................. 38 
5.5. 
Subject and Study Completion .................................................................... 39 
6.
STUDY TREATMENT ............................................................................................ 39 
6.1. 
Investigational Product and Other Study Treatment .................................... 39 
6.1.1. 
Medical Devices ........................................................................... 39 
6.2. 
Treatment Assignment ................................................................................ 40 
6.3. 
Planned Dose Adjustments ......................................................................... 40 
6.4. 
Packaging and Labeling .............................................................................. 40 
6.5. 
Preparation/Handling/Storage ..................................................................... 40 
6.5.1. 
DTG Film-Coated Tablets ............................................................ 40 
6.5.2. 
DTG Dispersible Tablets .............................................................. 41 
6.5.3. 
ABC/DTG/3TC Dispersible Tablets .............................................. 41 
6.5.4. 
ABC/DTG/3TC Immediate Release (Triumeq) Tablets ................. 42 

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6.6. 
Product Accountability and Disposal ........................................................... 43 
6.6.1. 
Special Precautions in the US for Disposal .................................. 43 
6.7. 
Compliance with Study Treatment Administration ....................................... 43 
6.8. 
Management of Study Treatment Overdose ............................................... 43 
6.9. 
Treatment after the End of the Study .......................................................... 43 
6.10. 
Meals and Dietary Restrictions ................................................................... 44 
6.11. 
Concomitant Medications and Non-Drug Therapies .................................... 44 
6.11.1. 
Permitted Medications ................................................................. 44 
6.11.2. 
Concomitant Medications Necessitating DTG Dose 
Adjustment ................................................................................... 45 
6.11.3. 
Prohibited Medications ................................................................. 45 
6.11.4. 
Additional considerations for ABC/DTG/3TC ................................ 46 
7.
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 46 
7.1. 
Study Schematic ......................................................................................... 47 
7.1.1. 
Parent Studies: Penultimate Visit Assessments ........................... 48 
7.2. 
Time and Events Table ............................................................................... 49 
7.3. 
Screening Visit ............................................................................................ 49 
7.4. 
Day 1 Visit .................................................................................................. 50 
7.5. 
Patient Monitoring ....................................................................................... 50 
7.5.1. 
Regular Visits (Every 12 Weeks) ................................................. 50 
7.5.2. 
Study Withdrawal/Discontinuation ................................................ 51 
7.6. 
Safety ......................................................................................................... 52 
7.6.1. 
Adverse Events (AE) and Serious Adverse Events (SAEs) .......... 52 
7.6.1.1. 
Time period and Frequency for collecting AE 
and SAE information ................................................... 52 
7.6.1.2. 
Follow-up of SAEs and AEs leading to 
discontinuation of IP ................................................... 52 
7.6.1.3. 
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................ 53 
7.6.1.4. 
Regulatory Reporting Requirements for SAEs ............ 53 
7.6.2. 
Pregnancy ................................................................................... 54 
7.6.2.1. 
Pregnancy Testing...................................................... 54 
7.6.2.2. 
Pregnancy Reporting .................................................. 54 
7.6.3. 
Physical Exams ........................................................................... 55 
7.6.4. 
Vital Signs .................................................................................... 55 
7.6.5. 
Suicidal Risk Monitoring ............................................................... 55 
7.6.5.1. 
Possible Suicidality Related Adverse Events .............. 55 
8.
DATA MANAGEMENT ........................................................................................... 56 
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES ................................. 56 
9.1. 
Hypotheses ................................................................................................. 56 
9.2. 
Sample Size Considerations ....................................................................... 56 
9.3. 
Data Analysis Considerations ..................................................................... 56 
9.3.1. 
Analysis Populations .................................................................... 56 
9.3.2. 
Interim Analysis ........................................................................... 56 
9.4. 
Key Elements of Analysis Plan ................................................................... 56 
10. STUDY GOVERNANCE CONSIDERATIONS ........................................................ 57 
10.1. 
Posting of Information on Publicly Available Clinical Trial Registers ............ 57 

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10.2. 
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................ 57 
10.2.1. 
Children in care............................................................................ 58 
10.3. 
Quality Control (Study Monitoring) .............................................................. 59 
10.4. 
Quality Assurance ....................................................................................... 59 
10.5. 
Study and Site Closure ............................................................................... 59 
10.6. 
Records Retention ...................................................................................... 60 
10.7. 
Provision of Study Results to Investigators, Posting of Information 
on Publicly Available Clinical Trials Registers and Publication .................... 61 
11. REFERENCES ....................................................................................................... 62 
12. APPENDICES ........................................................................................................ 64 
12.1. 
Appendix 1 – Abbreviations and Trademarks .............................................. 64 
12.2. 
Appendix 2 – Dosing Tables ....................................................................... 67 
12.2.1. 
Tivicay DTG Film Coated Tablets ................................................ 67 
12.2.2. 
DTG Dosing Table for subjects transitioning from parent 
study P1093 ................................................................................. 67 
12.2.3. 
ABC/DTG/3TC Dosing table for subjects transitioning from 
parent study P2019 ...................................................................... 68 
12.3. 
Appendix 3 – Pregnancy ............................................................................. 69 
12.3.1. 
Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential (FRP) .............. 69 
12.3.2. 
Collection of Pregnancy Information ............................................ 69 
12.4. 
Appendix 4 – Liver Safety – Study Treatment Restart Guidelines ............... 71 
12.4.1. 
Drug Restart Following Transient Resolving Liver Events 
Not Related to Study Drug ........................................................... 71 
12.5. 
Appendix 5 – Liver Safety – Checklist for Drug Restart Approval or 
Refusal ....................................................................................................... 72 
12.6. 
Appendix 6 – Toxicity Management ............................................................ 73 
12.6.1. 
Specific Toxicities/Adverse Event Management ........................... 75 
12.6.1.1. Decline in Renal Function ........................................... 75 
12.6.1.2. Liver Chemistry Stopping and Follow-up 
Criteria ........................................................................ 75 
12.6.1.3. Restarting Study Drug ................................................ 75 
12.6.1.4. Allergic reaction .......................................................... 75 
12.6.1.5. Rash ........................................................................... 75 
12.6.1.6. Hypertriglyceridemia/Hypercholesterolemia ................ 76 
12.6.1.7. Co-infection with TB ................................................... 76 
12.6.1.8. Subjects Co-infected with Hepatitis B Virus 
(HBV) ......................................................................... 77 
12.6.1.9. ABC Hypersensitivity .................................................. 78 
12.6.1.9.1. Reporting of ABC Hypersensitivity 
Reactions ............................................... 79 
12.7. 
Appendix 7 – Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events ............................ 80 
12.7.1. 
Definition of Adverse Events ........................................................ 80 
12.7.2. 
Definition of Serious Adverse Events ........................................... 81 
12.7.3. 
Recording of SAEs and AEs leading to discontinuation of 
IP ................................................................................................. 82 
12.7.4. 
Evaluating AEs and SAEs ............................................................ 82 

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12.7.5. 
Reporting of SAEs and AEs leading to discontinuation of 
IP to GSK/ViiV Healthcare/PPD ................................................... 84 
12.7.6. 
Reporting COVID-19 Related SAEs and AEs Leading to 
Treatment Discontinuation ........................................................... 84 
12.8. 
Appendix 8 – COVID-19 Pandemic and Study Guidance ............................ 85 
12.8.1. 
COVID -19 Experimental Agents ................................................. 85 
12.8.2. 
COVID-19 Specific Data Capture ................................................. 85 
12.9. 
Appendix 9 – CDC and WHO Classification Systems for HIV-1 
Infections .................................................................................................... 88 
12.10. Appendix 10 – DAIDS Toxicity Scales ........................................................ 89 
12.11. Appendix 11 – Country Specific Requirements ........................................... 90 
12.12. Appendix 12 – Protocol Amendment History ............................................... 91 

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1.
PROTOCOL SYNOPSIS FOR STUDY 205858
Rationale 
There is an unmet medical need for novel and potent antiretroviral therapy (ART) for 
children living with human immunodeficiency virus (HIV) infection, and research 
continues to assess new compounds in the pediatric population. The purpose of this 
pediatric study is to provide continued access to age appropriate formulations of 
dolutegravir (DTG), either as single entity DTG (Tivicay or Tivicay PD) or as a part of 
the fixed dose combination (FDC) ABC/DTG/3TC (Triumeq or ABC/DTG/3TC 
dispersible tablets), for eligible subjects who have completed either the P1093, or P2019 
parent study.  
Eligible subjects will have evidence of virological control at the time of completion of the 
parent studies and will have tolerated Investigational Product (IP) (single entity DTG 
[Tivicay or Tivicay PD], ABC/DTG/3TC FDC [Triumeq or ABC/DTG/3TC dispersible 
tablet]), in the parent studies without significant toxicities.  
Objective(s)/Endpoint(s) 
Objectives 
Endpoints 
Primary 
•
Incidence and severity of serious adverse
events (SAEs) and any clinical or
laboratory adverse events leading to
discontinuation of IP (DTG, or
ABC/DTG/3TC FDC).
•
To provide access to age appropriate
formulations of dolutegravir (DTG),
either as single entity DTG or as fixed
dose combination (FDC)
abacavir/dolutegravir/lamivudine
(ABC/DTG/3TC), in an open-label
protocol to eligible subjects who have
completed the P1093, or P2019 parent
studies.
Secondary 
•
To assess any serious adverse events
(SAEs) and any clinical or laboratory
adverse events that lead to the
discontinuation of IP (DTG, or
ABC/DTG/3TC FDC).
Overall Design 
This is a non-randomized, open-label, multi-center treatment rollover study.  
Single entity DTG in age appropriate formulations will be provided to eligible subjects 
transitioning from parent study P1093.  Sites participating in P1093 and this rollover 
study are in the following countries: Botswana, Brazil, Kenya, South Africa, Tanzania, 
Thailand, Uganda, United States and Zimbabwe. 

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ABC/DTG/3TC in age appropriate formulations will be provided to eligible subjects 
transitioning from parent study P2019.  Sites participating in P2019 and this rollover 
study are in the following countries: Botswana, South Africa, Thailand and the United 
States.  
Treatment Arms and Duration 
This study will have 2 treatment arms. One treatment arm will provide age appropriate 
formulations of single entity DTG to eligible subjects from the P1093 parent study. The 
second treatment arm will provide age appropriate formulations of DTG as the fixed dose 
combination ABC/DTG/3TC to eligible subjects from the P2019 parent study.  IP will be 
provided to each subject in this rollover study until any one or more of the following 
events occur:  
• 
Until age-appropriate formulations of DTG, or ABC/DTG/3TC are available 
from some other source (e.g. government programs, aid programs, assistance 
programs etc.) to a subject; OR 
• 
Until a subject is no longer deriving benefit from treatment; OR 
• 
Until a subject meets a protocol-defined reason for discontinuation; OR 
• 
Until development of DTG, or ABC/DTG/3TC is terminated. 
Type and Number of Subjects 
The subjects will be eligible patients from parent studies, P1093 and P2019. Based on the 
design of the parent studies, a maximum of 300 pediatric subjects could enroll in this 
study.  
Analysis 
No formal hypothesis testing will be performed. Data will provide only descriptive 
information on safety and tolerability. 
 

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2. 
INTRODUCTION 
Dolutegravir (DTG) is a potent integrase strand transfer inhibitor (INSTI).  DTG 50 mg 
film coated tablets, and DTG 5 mg dispersible tablets for oral suspension (marked as 
Tivicay PD in the US), are approved in most markets. The bioavailability of film coated 
tablets and dispersible tablets is not comparable; therefore, they must not be used as 
direct replacements. For example, the recommended adult dose for film coated tablets is 
50 mg versus 30 mg for dispersible tablets. Patients changing between film-coated and 
dispersible tablets should follow the dosing recommendations that are specific for the 
formulation. 
 
Abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) is a fixed dose combination regimen 
containing two nucleoside reverse transcriptase inhibitors (NRTIs) and DTG.  
ABC/DTG/3TC immediate release tablets (DTG 50 mg/ABC 600 mg/3TC 300 mg) are 
marketed as Triumeq.  
Both DTG and ABC/DTG/3TC have been developed for the treatment of human 
immunodeficiency virus type 1 (HIV-1) and are approved for use in adults and 
adolescents in most markets.  
• DTG is currently approved by the United States Food and Drug Administration 
(FDA) and the European Medicines Agency (EMA) for adults and for children 
aged at least 4 weeks and weighing at least 3 kg; and is approved in other markets 
for children greater than 6 years of age and at least 15 kg weight. Studies of DTG 
neonates are ongoing.     
• ABC is approved for adults and for children as young as 3 months of age.  
• 3TC is approved for adults and for children from birth.  
• ABC/DTG/3TC immediate release tablets are approved for use in adults and 
children weighing at least 40 kg (the EMA approval for pediatric use is limited to 
children at least 12 years of age). 
• The ABC/DTG/3TC immediate release tablet was approved for use in pediatric 
patients weighing 25 kg and above in the US, and ABC/DTG/3TC dispersible 
tablet (ABC 60 mg/DTG 5 mg/3TC 30) weight-based dosing was approved for 
use in patients weighing at least 10 kg in the US.   Additional marketing 
applications for the ABC/DTG/3TC dispersible tablet and immediate release 
tablets for pediatric patients are under review by the EMA. 
The purpose of this open label study is to provide continued access to age appropriate 
formulations of DTG, either as single entity DTG or as part of fixed dose 
combination ABC/DTG/3TC, for eligible subjects who previously participated in 
DAIDS sponsored parent studies P1093, or P2019 and who cannot locally access age 
appropriate formulations of DTG or ABC/DTG/3TC in the public sector.  
• 
Study P1093 is a Phase 1/2 multi-centre, open-label non-comparative 
intensive pharmacokinetic, safety, tolerability and antiviral activity study of DTG 
in combination with optimized background regimens in HIV-1 infected infants, 
children and adolescents.   

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• 
Study P2019 is a Phase 1/2 multi-centre, open-label, non-comparative, 
intensive pharmacokinetic, safety, tolerability and antiviral activity study of 
ABC/DTG/3TC dispersible and immediate release tablets in HIV-1-infected 
children.  
Eligible subjects are those who have continued benefit from IP as evidenced by 
virological control at the time of completion of the parent studies and who will have 
tolerated Investigational Product (IP) (single entity DTG [Tivicay or Tivicay PD], 
ABC/DTG/3TC [Triumeq or ABC/DTG/3TC dispersible tablets], in the parent study 
studies without significant toxicities. 
2.1. 
Study Rationale 
Children living with HIV infection require access to potent ARV regimens. The purpose 
of this study is to provide continued access to IP for eligible subjects who have 
completed the parent studies and continue to benefit from IP administration as evidenced 
by virologic control at the time of completion of the parent studies. Subjects will receive 
their age/weight appropriate dose of IP as defined in the parent study; hence, no PK 
sampling will be performed. 
2.2. 
Brief Background 
DTG as an oral tablet formulation has been approved for the treatment of HIV infection 
in most countries around the world and is now recommended as a component of first line 
therapy in global treatment guidelines [DHHSa, 2019; EACS, 2018; WHO, 2018]. 
In addition to being marketed as the Tivicay single-entity film coated tablet and as 
Tivicay or Tivicay PD single entity dispersible tablet, DTG is also a component of the 
fixed-dose combination product Triumeq [DTG/abacavir (ABC)/lamivudine(3TC)]. 
ABC and 3TC form the backbone of several recommended ART regimens.  These 
medications are available separately in tablet and liquid formulations and have also been 
co-formulated in fixed dose combination tablets (ABC/3TC).  
Previous experience in adults has demonstrated that the exposure to DTG, ABC and 3TC 
in a fixed dose combination formulation is consistent with each drug administered 
individually. This information was provided as part of the application for Triumeq. 
Therefore, the DTG dosing recommendations are not expected to differ when DTG is 
administered in fixed dose combination.  
Parent Study P1093 (ING112578)- Single entity DTG (Tivicay and Tivicay PD) 
Pediatric study P1093 (ING112578) is being conducted by the International Maternal 
Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) under sponsorship by 
the Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of 
Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD).  
Study P1093 evaluates the safety, tolerability, PK and antiviral activity of DTG in ART-
naïve and ART-experienced children and adolescents in various pediatric subsets defined 

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by age and type of formulation. Types of formulations included in this study are film 
coated tablets, pediatric granules and dispersible tablets (DT). The DTG granule 
formulation is no longer being developed for licensure. The study is closed to further 
accrual; 181 children enrolled. 
Study P1093 generated primary data to serve as the basis of pediatric dosing approvals 
for children from 4 weeks of age.  
The P1093 parent protocol includes a 48-week treatment phase, and a long-term safety 
follow-up up to 192 weeks. As subjects complete the P1093 study, they may require 
continued access to IP until age appropriate formulations of the drug become available in 
their markets. This rollover study will provide this needed access for children who meet 
entry requirements.  
At or after the Week 180 visit (penultimate study visit), subjects who are deriving benefit 
from IP may screen for the 205858 rollover study. If the subject is eligible, the initial Day 
1 Visit in 205858 may overlap with the Week 192 visit for P1093. Parent Study P2019 
(205860)- ABC/DTG/3TC 
The P2019 study includes a 48-week treatment phase, with primary visits at Weeks 1, 4, 
12, 24, 36 and 48 weeks.  At or after the Week 36 visit (penultimate visit in the treatment 
phase), subjects who are deriving benefit from IP may screen for the 205858 rollover 
study. If the subject is eligible, the initial Day 1 Visit in 205858 may overlap with the 
Week 48 visit for P2019.  Eligible subjects who complete the Week 48 visit before the 
rollover study is open to P2019 enrolment, may remain in the P2019 study for up to an 
additional 96 weeks until the rollover study is available.  

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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• Incidence and severity of serious adverse 
events (SAEs) and any clinical or 
laboratory adverse events leading to 
discontinuation of IP (DTG, or 
ABC/DTG/3TC FDC). 
• To provide access to age appropriate 
formulations of dolutegravir (DTG), 
either as single entity DTG or as fixed 
dose combination (FDC) 
abacavir/dolutegravir/lamivudine 
(ABC/DTG/3TC), in an open-label 
protocol to eligible subjects who have 
completed the P1093, or P2019 parent 
studies. 
Secondary 
• To assess any serious adverse events 
(SAEs) and any clinical or laboratory 
adverse events that lead to the 
discontinuation of IP (DTG, or 
ABC/DTG/3TC FDC). 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a non-randomized, open-label, multi-center rollover study with two treatment 
arms.  The purpose of this study is to provide continued access to IP for eligible subjects 
who have completed DAIDS sponsored parent studies P1093 or P2019.  
Continued access to DTG will be provided as follows: 
• Arm 1: Subjects from the P1093 parent study will continue to receive single entity 
DTG (Tivicay or Tivicay PD).  
• Arm 2: Subjects from the P2019 parent study will continue to receive 
ABC/DTG/3TC (Triumeq or ABC/DTG/3TC dispersible tablets). 
The duration of subject participation in the study will extend until age appropriate 
formulations of  DTG or ABC/DTG/3TC receive local (by country) regulatory approval 
and are available commercially in those countries or other availability occurs from 
another source (e.g. government programs, aid programs, assistance programs, etc.). 
Patients may be enrolled after all screening procedures have been completed and 
eligibility reviewed and documented in the patient’s medical records. In most cases, the 
Screening visit will overlap with the subject’s penultimate visit on the parent study (at or 
after Week 180 of P1093, or at or after Week 36 of the P2019 study). Patients who are 
eligible may enroll and will be seen in the clinic every 12 weeks for a safety evaluation 
and to receive IP.  IP is provided by ViiV Healthcare. Only DTG and ABC/DTG/3TC 
will be made available through this rollover protocol. Provision of other ARVs as part of 

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the background regimen are not considered IP and will not be supplied. It is the 
responsibility of the investigator to source the ARVs of the background regimen locally. 
4.2. 
Treatment Arms and Duration 
IP will be provided to each subject on this rollover study until any one or more of the 
following events occur: 
•
Until age-appropriate formulations of DTG or ABC/DTG/3TC are available
from some other source (e.g. government programs, aid programs, assistance
programs etc.) for a subject; OR
•
Until a subject is no longer deriving benefit from treatment; OR
•
Until a subject meets a protocol-defined reason for discontinuation (See Section
5.3)
•
Until development of DTG or ABC/DTG/3TC is terminated.
Once subjects enter this rollover study, they will be seen in clinic every 12 weeks for 
safety visits until one of the above criteria are filled. Site investigators will monitor 
safety, and collect and report SAEs, pregnancy reports and any AE that leads to the 
discontinuation of IP to PPD, the contract research organization charged with conducting 
the study. SAEs, pregnancies, and events leading to discontinuation of IP (including liver 
stopping criteria) will be collected and reported to PPD within 24 hours of the 
investigator becoming aware of the event.  
Procedures other than those required to confirm study eligibility and assessment of 
study endpoints, will be performed as per local standard of care (SoC) (including 
laboratory evaluations). 
4.2.1. 
DTG for subjects transitioning from P1093 
This rollover study will utilize 2 formulations of DTG for subjects transitioning from the 
P1093 study.  DTG film coated tablets and dispersible tablets will be provided to subjects 
by age and weight bands.  Specific weight-based dosing instructions can be found in the 
current dosing tables in Section 12.2 (Appendix 2). 
4.2.2. 
ABC/DTG/3TC for subjects transitioning from P2019 
Two formulations of ABC/DTG/3TC will be utilized for subjects transitioning from the 
P2019 study. Immediate release tablets and dispersible tablets will be provided to 
subjects by weight bands.   
ABC/DTG/3TC tablets (60 mg/5 mg/30 mg dispersible tablets or 600 mg/50 mg/300 mg 
immediate release [Triumeq] tablets) will be provided to subjects by age and weight 
bands.  Specific weight -based ABC/DTG/3TC dosing instructions for subjects 
transitioning from P2019 can be found in the current dosing table in Section 12.2  
(Appendix 2). 

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In addition to the triple-agent fixed dose combination formulations noted above, ViiV 
Healthcare Ltd will provide DTG 5mg DT and DTG 50mg film coated tablets for use 
among children who required dose adjustments in the P2019 parent study that cannot be 
achieved with the triple-agent fixed dose combination formulations.  DTG 10mg and 
25mg tablets will not be provided and must be supplied locally. Single entity ABC and 
3TC are not considered IP, will not be provided by the study, and must be supplied 
locally.  Deviations from this dosing table are allowed only if alternative dosing was 
approved and implemented within the P2019 parent study. 
4.2.3. 
Weight based dose adjustments for all subjects 
Weight for all subjects will be measured and recorded at each visit to verify the subject is 
receiving the appropriate dose based on the current dosing tables (Appendix 2). If a 
subject’s weight change requires a dose adjustment, the dose adjustment should be made. 
The local PPD medical monitor must be notified, although approval for a weight-based 
dose adjustment is not required. Dose adjustments for weight decreases will only be made 
if the weight decrease persists for 2 consecutive study visits. 
4.3. 
Type and Number of Subjects 
All subjects from the P1093 and P2019 studies who meet the screening eligibility criteria 
and are unable to access age appropriate formulations of IP locally, will be allowed to 
enroll in this study and will be considered evaluable. Based on the design of the parent 
studies, a maximum of 300 pediatric subjects with HIV could enroll in this study.  
4.4. 
Design Justification 
A rollover study is needed in order to provide access to DTG or ABC/DTG/3TC FDC, 
until age appropriate formulations are approved locally and are available commercially or 
other availability occurs from another source (e.g. government programs, aid programs, 
assistance programs, etc.). 
4.5. 
Dose Justification 
The doses for this study have been determined by the results of the parent studies. 
Current weight-based dosing tables can be found in Appendix 2. 
If new dosing for DTG or ABC/DTG/3TC is licensed during the conduct of this study, 
subjects will be allowed to switch to these doses as allowed by local practice.  
4.6. 
Benefit:Risk Assessment 
Summaries of findings from both clinical and non-clinical studies conducted with DTG in 
the treatment of HIV-infected Adult and Pediatric subjects can be found in the most 
current version of the DTG Investigator’s Brochure (IB) [ViiV Healthcare Ltd and local 
DTG product labeling]. The following section outlines the risk assessment and mitigation 
strategy for DTG in this protocol. 

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4.6.1. 
Risk Assessment for DTG 
Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy1, 2 
Investigational Product (IP) [DTG] 
Refer to IB for additional information on DTG  
Hypersensitivity 
(HSR) and rash 
HSR has been observed 
uncommonly with DTG. Rash was 
commonly reported in DTG Phase 
2b/3 clinical trials; episodes were 
generally mild to moderate in 
intensity; no episodes of severe rash, 
such as Stevens-Johnson Syndrome 
(SJS), Toxic Epidermal Necrolysis 
(TEN) and erythema multiforme were 
reported. 
Subjects with history of allergy/sensitivity to any 
of the study drugs are excluded (Section 5.2). 
 
Specific/detailed toxicity management guidance 
is provided for HSR (Section 12.6.1.4) and rash 
(Section 12.6.1.5). 
 
The subject informed consent form includes 
information on this risk and the actions subjects 
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, 
subjects must permanently discontinue study 
drug and be withdrawn from the study. 
Drug induced 
liver injury (DILI) 
and other 
clinically 
significant liver 
chemistry 
elevations 
Non-clinical data suggested a 
possible, albeit low, risk for 
hepatobiliary toxicity with DTG. Drug-
related hepatitis is considered an 
uncommon risk for ART containing 
DTG regardless of dose or treatment 
population. For subjects with 
hepatitis B virus (HBV) and/or 
hepatitis C virus (HCV) co-infection, 
improvements in immunosuppression 
as a result of HIV virologic and 
immunologic responses to DTG-
containing ART, along with 
inadequate therapy for HBV co-
infected subjects, likely contributed to 
significant elevations in liver 
chemistries.   
Subjects meeting the following criteria during 
the screening period are excluded from 
participating (Section 5.2). 
• 
Alanine aminotransferase ≥5 times ULN or 
ALT 3xULN and bilirubin ≥1.5xULN (with 
>35% direct bilirubin) 
Investigators should consult current treatment 
guidelines when considering choice of 
nucleoside reverse transcriptase inhibitor 
(NRTIs) for subjects with chronic HBV infection. 
Additional treatment considerations should be 
guided by local treatment guidelines. Adequate 
HBV therapy must be administered to subjects 
with chronic HBV infection (Section 12.6.1.8). 
 
Specific/detailed liver stopping criteria and 
toxicity management guidance is provided for 
suspected DILI or other clinically significant liver 
chemistry elevations (Section 12.6.1.2).   
Theoretical 
serious drug 
interaction with 
dofetilide 
pilsicainide and 
fampridine 
Co-administration of DTG may 
increase 
dofetilide/pilsicainide/fampridine 
plasma concentration via inhibition of 
organic cation transporter 2, resulting 
in potentially life-threatening toxicity.  
The co-administration of DTG with 
dofetilide/pilsicainide/fampridine is prohibited in 
the study (Section 6.11.3). 

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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy1, 2 
Psychiatric 
disorders 
Psychiatric disorders including 
suicide ideation and behaviors are 
common in HIV-infected patients. 
The psychiatric profile for DTG 
(including suicidality, depression, 
bipolar and hypomania, anxiety and 
abnormal dreams) was similar or 
favorable compared with other ART.  
The reporting rate for insomnia was 
statistically higher for blinded 
DTG+ABC/3TC compared to 
efavirenz (EFV)/ tenofovir  
(TDF)/emtricitabine (FTC) in 
ING114467; however, this was not 
duplicated in any other Phase 2b/3 
study conducted with DTG.   
Because of the elevated risk in the HIV- infected 
population, treatment emergent assessment of 
suicidality should be monitored during this 
study. Investigators are advised to consider 
mental health consultation or referral for 
subjects who experience signs of suicidal 
ideation or behaviour, which should be reported 
using a specific electronic Case Report Form 
(eCRF) module (Section 7.6.5). 
In addition, the subject informed consent form 
includes information on this risk of depression 
and suicidal ideation and behaviors. 
Neural tube 
defects 
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 
five out of 6,748 deliveries (0.07%) to 
mothers who started non-DTG 
containing regimens during 
pregnancy. 
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 3, Section 12.3.1) from 30 
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. Females who are breastfeeding or plan to 
become pregnant or breastfeed during the 
study are excluded. 
3. Females 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. 
Pregnancy status is monitored at every 
study visit 

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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy1, 2 
1. 
Careful monitoring of all SAEs and AEs leading to treatment discontinuation will be conducted using 
relevant event reports and will be managed appropriately including, but not limited to, withdrawal of IP, 
and will be followed to resolution as per standard Medical Monitoring practices (See Section 7.6.1.1).   
2. 
SAEs, AEs leading to treatment discontinuation and pregnancies will be routinely reviewed by PPD 
and ViiV Healthcare/GSK. This will include in-stream review of data from this clinical trial on a routine 
basis. 
 
 

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4.6.2. 
Risk Assessment for ABC/DTG/3TC  
Potential Risk of 
Clinical 
Significance 
Data/Rationale for Risk 
Mitigation Strategy 
Refer to Investigator Brochure and/or approved Local Prescribing Information for additional 
information on ABC/DTG/3TC 
Hypersensitivity 
(including 
abacavir 
hypersensitivity 
reaction) and 
rash 
A well characterized, idiosyncratic, drug-
related hypersensitivity reaction is the 
most important risk associated with 
ABC. Although the diagnosis of ABC 
HSR is based on clinical symptoms, 
exclusion of individuals found to carry 
the human leucocyte antigen (HLA)-
B*5701 allele from ABC therapy reduces 
the risk of hypersensitivity reactions. 
Rash, including Stevens-Johnson 
syndrome, toxic epidermal necrolysis, 
and erythema multiforme have been 
reported in patients taking ABC.   
Hypersensitivity reactions have been 
observed uncommonly with DTG. Rash, 
generally mild to moderate in intensity, 
was commonly reported in DTG Phase 
2b/3 clinical trials. No episodes of 
severe rash, such as Stevens-Johnson 
syndrome, toxic epidermal necrolysis 
and erythema multiforme were reported. 
Data on hypersensitivity reactions for 
DTG and DTG+ABC/3TC fixed dose 
combination suggest that there will not 
be additional risk from a hypersensitivity 
reaction in HLA-B*5701 negative 
subjects receiving the ABC/DTG/3TC 
fixed dose combination. 
Screening for the carriage of HLA-B*5701 
is recommend when such screening is 
considered SoC. Subjects positive for HLA-
B*5701 are excluded from participating. 
Additionally, subjects with history or 
presence of allergy to any of the study 
drugs or their components are excluded 
(Section 5.2). 
Specific/detailed toxicity management 
guidance is provided for suspected 
hypersensitivity reactions with DTG or 
ABC, and skin reactions without systemic 
involvement (Section 12.6.1.9). 
The subject informed consent form 
includes information on this risk and the 
actions subjects should take in the event of 
a hypersensitivity reaction or associated 
signs and symptoms.  
Subjects are to be reminded to read the 
ABC hypersensitivity reaction Warning 
Card provided, and of the importance of 
keeping this card with them at all times. 
All subjects in the P2019 parent study will 
have been screened negative for HLA-
B*5701 at entry into that study. 
Drug induced 
liver injury and 
other clinically 
significant liver 
chemistry 
elevations 
Non-clinical data suggested a possible, 
albeit low, risk for hepatobiliary toxicity 
with DTG. Drug-related hepatitis is 
considered an uncommon risk for 
antiretroviral therapy containing DTG 
regardless of dose or treatment 
population.  
For subjects with hepatitis B virus and/or 
hepatitis C virus co-infection, 
improvements in immunosuppression 
because of HIV virologic and 
immunologic responses to DTG-
containing antiretroviral therapy, along 
with inadequate therapy for hepatitis B 
virus co-infected subjects, likely 
contributed to significant elevations in 
Subjects meeting any of the following 
criteria during the screening period are 
excluded from participating (Section 5.2) 
• Alanine aminotransferase 5 times 
ULN or ALT 3xULN and bilirubin 
1.5xULN (with >35% direct bilirubin) 
• Unstable liver disease, cirrhosis and/or 
known biliary abnormalities (except for 
hyperbilirubinemia or jaundice due to 
Gilbert's syndrome or asymptomatic 
gallstones) 
• Subjects positive for hepatitis B virus in 
the parent study (hepatitis B virus 
surface antigen positive) 

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Potential Risk of 
Clinical 
Significance 
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Mitigation Strategy 
liver chemistries.   
Current treatment guidelines do not 
recommend mono-therapy with 3TC for 
patients with hepatitis B virus infection. 
Additionally, discontinuation of 3TC in 
hepatitis B virus infected subjects can 
result in severe exacerbations of 
hepatitis B virus.  
 
For subjects co-infected with hepatitis C 
virus and HIV, [some] treatment 
guidelines recommend that the hepatitis 
C virus infection is treated first before 
starting treatment for the HIV. 
Additionally, interferon and/or ribavirin 
toxicity maybe frequent and difficult to 
differentiate causality from 
investigational product 
• Subjects with anticipated need for 
HCV therapy with interferon or 
any drugs that have potential for 
adverse drug:drug interactions 
with study treatment throughout 
the entire study period. 
Specific/detailed liver stopping criteria and 
toxicity management guidance is provided 
for suspected drug induced liver injury or 
other clinically significant liver chemistry 
elevations (Section 5.4.4 and Section 
12.4).  
Theoretical 
serious drug 
interaction with 
dofetilide, 
pilsicainide and 
fampridine 
Co-administration of DTG may increase 
dofetilide, pilsicainide or fampridine 
plasma concentration via inhibition of 
organic cation transporter 2, resulting in 
potentially life-threatening toxicity.  
The co-administration of DTG with 
dofetilide, pilsicainide or fampridine is 
prohibited in the study (Section 6.11.2). 
Psychiatric 
disorders 
Psychiatric disorders including suicide 
ideation and behaviours are common in 
HIV-infected patients. The psychiatric 
profile for DTG (including suicidality, 
depression, bipolar and hypomania, 
anxiety and abnormal dreams) was 
similar or favourable compared with 
other antiretroviral therapies.  
The reporting rate for insomnia was 
statistically higher for blinded 
DTG+ABC/3TC compared to 
efavirenz/tenofovir/emtricitabine in the 
SINGLE clinical study; however, this was 
not duplicated in any other VH 
Sponsored Phase 2b/3 study with DTG 
or ABC/DTG/3TC. 
Due to the elevated risk in the HIV-infected 
population, and reports in patients treated 
with integrase inhibitors, including DTG, 
treatment emergent assessment of 
suicidality will be monitored during this 
study.  Investigators are advised to 
consider mental health consultation or 
referral for subjects who experience signs 
of suicidal ideation or behaviour (Section 
7.6.5). 
Renal function  
Lamivudine is eliminated by renal 
excretion and exposure increases in 
patients with renal dysfunction. 
 
ABC/DTG/3TC FDC should not be used 
in participants with creatinine clearance 
of less than 30 mL/min because, whilst 
Known ≥Grade 3 laboratory toxicities (e.g. 
neutrophil count, hemoglobin, platelets, 
aspartate aminotransferase (AST), ALT, 
lipase, serum creatinine, eGFR and total 
bilirubin) would be considered exclusionary 
if identified at or after the penultimate 
parent study visit, prior to enrolment in the 

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Potential Risk of 
Clinical 
Significance 
Data/Rationale for Risk 
Mitigation Strategy 
no dosage adjustment of DTG or ABC is 
necessary in patients with renal 
impairment, dose reduction is required 
for the 3TC component. 
 
study. Repeat testing is allowed for 
eligibility determination.’ 
 
Participants who develop confirmed Grade 
4 creatinine clearance (<30 ml/min/1.73m2) 
should permanently discontinue study drug.  
Detailed toxicity management guidance is 
provided for participants who develop a 
decline in renal function (Section 5.4.3). 
 
4.6.3. 
Benefit Assessment 
DTG as an oral tablet formulation has been approved for the treatment of HIV infection 
in most countries around the world and is recommended as a component of first line 
therapy in global treatment guidelines (DHHSa, 2019; EACS, 2018; WHO, 2018).  In 
June 2020, the US FDA expanded the use of the already approved DTG 50 mg film-
coated tablet to pediatric patients weighing at least 20 kg and approved the DTG 
dispersible tablet for oral suspension for children as young as four weeks of age and 
weighing at least 3 kg.  
Data from the P1093 parent study are presented in the DTG IB. The safety, 
pharmacokinetics and effectiveness of Tivicay and Tivicay PD were evaluated in P1093, 
in 75 HIV-1 infected, treatment-naïve or treatment experienced, INSTI-naïve pediatric 
and adolescent subjects aged 4 to less than 18 years weighing at least 3 kg. Additional 
pharmacokinetics data were evaluated in 2 pharmacokinetic sub studies in ODYSSEY, an 
open-label randomized, non-inferiority trial to evaluate the safety, efficacy and, 
pharmacokinetic parameters of DTG plus 2 NRTIs compared with SoC in HIV-1 infected 
pediatric subjects younger than 18 years.  
Overall, the safety data in pediatric subjects from P1093 were comparable to those 
observed in adults. The pharmacokinetic parameters of Tivicay or Tivicay PD in pediatric 
subjects from P1093 and ODYSSEY were comparable to those of adults receiving 50 mg 
once daily or twice daily.  The effectiveness observed in P1093 is comparable to that of 
treatment experienced adult subjects.  
Safety and effectiveness of Tivicay or Tivicay PD have not been established in pediatric 
patients aged less than 4 weeks or weighing less than 3 kg or in any pediatric patients 
who are INSTI-experienced with documented or clinically suspected resistance to other 
INSTIs (e.g., raltegravir, elvitegravir). The ABC/DTG/3TC FDC, approved in multiple 
countries worldwide for the treatment of HIV-1 infection, provides a convenient once-
daily single tablet regimen, without need for a PK booster or food/fluid restrictions, and 
with limited safety implications resulting from theoretical or actual drug: drug 
interactions compared with other antiretroviral agents (including EFV and those requiring 
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4.6.4. 
Overall Benefit:Risk Conclusion 
Taking into account the measures taken to minimize risks to subjects participating in this 
study, the potential risks identified in association with long-term use of DTG based 
combination ART are justified by the anticipated benefits that may be afforded to HIV-1 
infected pediatric subjects continuing DTG-containing regimens as part of this study. 
5. 
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA 
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on DTG that may impact subject eligibility is provided in the 
current DTG IB. 
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. 

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5.1. 
Inclusion Criteria 
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply: 
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY  
1. Subjects must have completed participation in one of the following parent studies, for 
the duration noted: 
• P1093 parent study through at least Week 180 
• P2019 parent study through at least Week 48. 
2. Virological control at screening: 
a) Subjects in parent study P1093 must have virological control defined as 
HIV-1 RNA <400 c/mL at their penultimate visit (on or after the Week 180 
visit).  
b) Subjects in parent study P2019 must have virological control defined as 
HIV-1 RNA <200 c/mL at their penultimate visit (on or after Week 36). 
Note:  
▪ If the penultimate P1093; P2019 visit (on or after Week 180 for P1093; on or 
after Week 36 for P2019) indicates the possibility of virologic failure, a 
single retest can be completed in the parent study.  
– 
Results of the retest must be obtained and confirmed prior to the Day 1 
visit (the Day 1 visit overlaps with the final visit in each parent study).   
– 
If the retest indicates virologic control is present as noted above, 
eligibility is confirmed as long as the participant meets all other entry 
criteria.  
– 
Adherence issues should be addressed, and viral suppression must be 
confirmed prior to Day 1. 
3. Evidence of continued benefit from IP during the subject’s participation in the parent 
study (P1093 or P2019).  
– At screening, Investigators will submit a clinical summary verifying 
evidence of continued benefit from IP during the subject’s participation in 
the parent study (P1093 or P2019).  
– The summary will be submitted via the PPD ePIP system to the Study 
Medical Monitor who will review and confirm if the inclusion criterion 
has been met.  
– Confirmation from the Study Medical Monitor is required to meet this 
eligibility criterion 
SEX 
4. Males and Females 
All subjects who are engaging in sexual activity should be counselled on safer sexual 

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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. 
Females:  
Female subjects who are of childbearing potential and who are engaging in sexual 
activity that could lead to pregnancy, must agree to use one of the acceptable birth 
control methods listed in Appendix 3 (Section 12.3) until the last dose of study 
medication and completion of the Follow-up visit (4 weeks after the last dose). 
Condoms are recommended in addition, because their appropriate use is the only 
contraception method effective for preventing HIV-1 transmission. 
 
INFORMED CONSENT 
5. Parent or legal guardian or subject 18 years of age is able and willing to provide 
signed informed consent as described in Section 10.2 which includes compliance with 
the requirements and restrictions listed in the consent form and in this protocol.  
Where applicable, subjects must provide written assent. 
 
5.2. 
Exclusion Criteria 
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply: 
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER 
FUNCTION AND QTc INTERVAL)  
1. Confirmed virologic failure with evidence of resistance to: 
a) DTG in the P1093 parent study, or 
b) ABC, DTG or 3TC (with the exception of M184V) in the P2019 parent 
study 
2. Presence of any active Acquired Immunodeficiency Syndrome (AIDS) defining 
opportunistic infection. 
3. Known ≥Grade 3 laboratory toxicities (e.g. neutrophil count, hemoglobin, platelets, 
aspartate aminotransferase (AST), ALT, lipase, serum creatinine, eGFR and total 
bilirubin) would be considered exclusionary if identified at or after the penultimate 
parent study visit, prior to enrollment in the study. Repeat testing is allowed for 
eligibility determination. NOTE:  ≥Grade 3 total bilirubin is allowable, if the subject 
is on ATV.  
NOTE: Subjects with laboratory abnormalities considered unrelated to IP may be 
allowed to enter the study. Thus, if the laboratory abnormality persists upon repeat 
testing, the subject may be considered for study entry after consultation and approval 
of the study team. An exception to this note is for participants with confirmed 
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not be used. 
4. Previous permanent discontinuation from IP in the parent study due to toxicity, 
intolerance, or pregnancy. 
5. Known ALT ≥5xULN, OR ALT ≥3xULN AND bilirubin ≥1.5xULN (with >35% 
direct bilirubin) would be considered exclusionary if identified at or after the 
penultimate parent study visit, prior to enrolment in the study. Subjects with 
moderate to severe hepatic impairment (Class B or greater) as determined by Child-
Pugh classification should be excluded.  
6. Subjects positive for hepatitis B virus at any time prior to entry (hepatitis B virus 
surface antigen positive). 
7. Females who are pregnant or plan to become pregnant or breastfeed during the study.  
8. Subject is currently participating in or has participated in a study with a compound or 
device that is not commercially available within 30 days of signing informed 
consent, unless permission from the PPD Medical Monitor is granted. 
9. Presence of any history of allergy/sensitivity to any of the study drugs. 
10. Subjects transitioning from the P2019 study (taking ABC/DTG/3TC) who are HLA-
B*5701 positive based on documented testing at any time prior to entry. 
 
CONCOMITANT MEDICATIONS 
11. Use of any disallowed medications at time of screening (see Section 6.11.3 for a 
complete list of disallowed medications). 
12. Anticipated need for HCV therapy with interferon or any drugs that have potential 
for adverse drug:drug interactions with study treatment throughout the entire study 
period. 
 
RELEVANT HABITS 
13. Subject is unlikely to adhere to the study procedures, keep appointments, or is 
planning to relocate during the study. 
 
CONTRAINDICATIONS  
14. Clinical or symptomatic evidence of pancreatitis, as determined by the clinician 
 
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA 
15. Any condition (including but not limited to alcohol and drug use) that would, in the 
opinion of the site investigator, place the subject at an unacceptable risk of injury or 
render the subject unable to meet the requirements of the protocol. 
When there is a country specific label with an approved pediatric indication(s), 
please refer to the Local Product Information for Tivicay (DTG) or Triumeq 

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(ABC/DTG/3TC) for information on contraindications and drug interactions when 
making decisions about patient eligibility. 
5.3. 
Screening Failures 
Screen failures are defined as subjects who consent to participate in the study but do not 
meet inclusion/exclusion criteria. 
5.4. 
Withdrawal/Stopping Criteria 
5.4.1. 
Criteria for Study Discontinuation 
• 
The subject or legal guardian refuses further treatment and/or follow-up 
evaluations. 
• 
The subject fails to comply with the study requirements so as to cause harm to 
him/herself or seriously interfere with the validity of the study results. 
• 
The subject requires treatment with medications that are disallowed while on this 
study. 
• 
Non-adherence of medications including IP and/or background therapy as 
determined by Investigator. 
• 
The investigator or study medical monitor in consultation with the PPD Medical 
Monitor has determined that there would be no benefit to continue on-study and 
receive IP. 
Note: The Sponsor (ViiV Healthcare) advises against continuation of IP after 
confirmed VF due to the risk of INSTI resistance development. 
5.4.2. 
Criteria for IP Discontinuation 
• 
Pregnancy (intrauterine), regardless of termination status of pregnancy (see 
Section 7.6.2). As a reminder, females of reproductive potential who change their 
minds and desire to be pregnant should also be withdrawn from the study. 
• 
New data become available that indicate IP should be discontinued. 
• 
Drug toxicity that requires permanent IP discontinuation. 
• 
Liver toxicity where stopping criteria specified in Section 5.4.4 are met and no 
compelling alternate cause is identified. 
• 
Allergic reaction or rash criteria as specified in Section 12.6.1.4 and Section 
12.6.1.5, respectively, are met and no compelling alternate cause is identified. 
• 
The investigator determines that further participation would be detrimental to the 
subject's health or well-being. 
NOTE: In the event of treatment discontinuation, subjects will be asked to continue on 
study for 4 weeks after they discontinue IP and complete the Follow-up Visit. If an AE 
remains unresolved at the Follow-up Visit, the subject will continue to be followed until 
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A subject may withdraw from IP at any time upon the request of the parent(s)/guardian(s) 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral or administrative reasons. In addition, investigators should attempt to record 
the reason for withdrawal in the patient records. A Study Discontinuation eCRF must be 
completed. 
The following actions must be taken in relation to a subject who fails to attend the clinic 
for a required study visit: 
• 
The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible.  
• 
The site must counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study.  
• 
In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and if necessary a certified letter to the subject’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the subject’s medical record.  
• 
Should the subject continue to be unreachable, only then will he/she be considered 
to have withdrawn from the study with a primary reason of “Lost to Follow-up”.  
5.4.3. 
Management of Renal Toxicity 
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 four 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. 
When serum creatinine testing is performed, it is recommended that the eGFR rate should 
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 should 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 etc.) should be considered and a 
nephrology consult may be obtained. 
5.4.3.1. 
Creatinine 
It is recommended that subjects 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, 

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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. 
If the increase to 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 with 
the Study Medical Monitor to determine benefit risk of continuing with study drug. 
For a confirmed Grade 4 creatinine, 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. 
5.4.3.2. 
eGFR 
It is recommended that subjects 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 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 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. 
 
5.4.4. 
Liver Chemistry Stopping Criteria 
When there is a country specific label with an approved pediatric indication(s), 
please refer to the Local Product Information for Tivicay or Tivicay PD (DTG) or 
Triumeq (ABC/DTG/3TC) for information on the monitoring of liver function. In 

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other cases, recommendations for drug discontinuation during treatment are given 
below. 
In the event of a clinical picture suggestive of potential liver injury in a patient 
taking IP, patients must be investigated as clinically indicated. Failure by an 
investigator to monitor liver safety could impact on the continuation of the patient 
in this study. 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure subject safety and proper evaluation of liver event etiology during administration 
of IP and the follow-up period (in alignment with the FDA premarketing clinical liver 
safety guidance). 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf 
For any subject meeting one of the criteria outlined in Table 1 or Table 2, or if the 
Investigator believes that it is in the best interest of patients, the Investigator must follow 
the actions noted below  Recommended follow up assessments are also outlined in Table 
1. 

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Table 1 
Liver Chemistry Stopping Criteria- Liver Stopping Event 
ALT absolute 
ALT  8xULN 
ALT increase 
ALT  5xULN but <8xULN persists for 2 weeks (with bilirubin <2xULN and no 
signs or symptoms of acute hepatitis or hypersensitivity) 
Bilirubin1, 2 
ALT  3xULN and bilirubin  2xULN (>35% direct bilirubin)  
 
INR2  
ALT  3xULN and International normalised ratio (INR)>1.5, if INR measured 
Cannot 
Monitor 
ALT  5xULN but <8xULN and cannot be monitored weekly for >2 weeks 
(See Table 2 for actions where subjects CAN be monitored weekly for >2 weeks) 
Symptomatic3 ALT  3xULN (if baseline ALT is ULN) with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity 
ALT  3x baseline (if baseline ALT>ULN) with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity 
Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Recommended Follow Up Assessments 
• Immediately hold IP.  
• If a causal relationship between the liver 
event and IP cannot be ruled out, then IP 
must be permanently discontinued and 
the Subject not rechallenged due to the 
risk of a recurrent reaction.   
• Report the event to the PPD by telephone 
within 24 hours. 
• Events of possible drug-induced liver injury 
with hyperbilirubinemia2 will be reported to 
PPD as serious adverse events using the 
serious adverse event case report form. 
• Complete the liver event case report form for 
all events meeting liver stopping criteria, and 
submit to PPD within one week of first 
becoming aware of the event 
• Liver event follow up assessments are 
recommended.  
• Monitor the subject until liver chemistries 
resolve, stabilise, or return to within baseline 
• 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 case 
report form 
Serum acetaminophen adduct High 
Performance Liquid Chromatography assay 
(quantifies potential acetaminophen 
contribution to liver injury in subjects with 
definite or likely acetaminophen use in the 
preceding week [James, 2009]).  The site must 

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(see MONITORING below). 
• If the liver event has a clear underlying 
alternative cause, other than drug-
induced liver injury, then Drug Restart 
may be considered by ViiV (for exception 
see Section 12.5). 
• If restart is not allowed or not granted, 
permanently discontinue IP and may 
continue subject in the study for any protocol 
specified follow up assessments. 
 
MONITORING: 
• It is recommended that the site make every 
reasonable attempt to have subjects return to 
clinic within 24 hours for repeat liver 
chemistries (include ALT, aspartate 
aminotransferase, alkaline phosphatase, 
bilirubin) and perform liver event follow up 
assessments described to the right.  
• A specialist or hepatology consultation is 
recommended. 
• It is recommended that the site monitor 
subjects twice weekly until liver chemistries 
resolve, stabilise or return to within baseline. 
contact the medical monitor when this test is 
required. NOTE: not required in China 
• Serum creatinine kinase and lactate 
dehydrogenase. 
• Fractionate bilirubin, if total bilirubin 
1.5xULN. 
• Complete blood count with differential to 
assess eosinophilia. 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (or gamma 
globulins). 
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease.  Liver Imaging and/or Liver 
Biopsy data will be collected in the case 
report form. 
• Record use of concomitant medications 
within the site source documentation, 
including acetaminophen, herbal 
remedies, other over the counter 
medications. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin 
fractionation is not immediately available, discontinue IP for that subject if ALT  3xULN and 
bilirubin  2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record 
presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations 
and suggesting liver injury.  
2. All events of ALT  3xULN and bilirubin  2xULN (>35% direct bilirubin) or ALT  3xULN and 
INR>1.5, if INR measured which may indicate severe liver injury must be reported as a 
serious adverse event (excluding studies of hepatic impairment or cirrhosis); INR 
measurement is not required and the threshold value stated will not apply to subjects receiving 
anticoagulants 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, or jaundice) or believed to be related to 
hypersensitivity (such as fever, rash or eosinophilia).  Record the appearance or worsening of 
any such clinical symptoms on the adverse event report form if the adverse event has led to 
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Table 2 
Liver Chemistry Increased Monitoring Criteria 
 
Criteria 
Actions 
ALT 5xULN and <8xULN and 
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for >2 weeks. 
• Notify the PPD medical monitor within 24 hours 
of learning of the abnormality to discuss subject 
safety.  
• Subject can continue IP  
• It is recommended that the subject return weekly 
for repeat liver chemistries (ALT, aspartate 
aminotransferase, alkaline phosphatase, bilirubin) 
until resolution, stabilisation (ALT <5×ULN on 2 
consecutive evaluations) or return to within 
baseline   
• If at any time subject meets the liver chemistry 
stopping criteria, proceed as described above 
 
5.4.5. 
Study Treatment Restart and Rechallenge  
‘Rechallenge’ refers to resuming study treatment following drug induced liver injury 
(DILI). Following DILI, 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.   
In the event of a discontinuation of IP for a Liver Stopping Event, subjects should not be 
rechallenged with IP due to the risks associated with rechallenge. 
‘Drug restart’ refers to resuming study treatment following a Liver Stopping Event in 
which there is a clear underlying cause (other than drug induced liver injury) of the liver 
event (e.g. biliary obstruction, pancreatic events, hypotension, acute viral hepatitis).  
If subject meets liver chemistry stopping criteria, do not restart subject with IP unless: 
• 
ViiV Healthcare Safety and Labeling Committee (VSLC) approval is granted 
• 
Independent Ethics Committee (IEC) and/or Institutional Review Board (IRB) 
approval is obtained, if required, and 
• 
Separate consent for treatment restart is signed by the subject 
If VSLC approval to restart subject with study treatment is not granted, then subject 
must permanently discontinue IP and may continue in the study for protocol-specified 
follow up assessments. 
For detailed guidance, refer to: 

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• Section 12.4 (Appendix 4) Liver Safety Treatment Restart Guidelines 
• Section 12.5 (Appendix 5) “Checklist for Drug Restart Approval or Refusal”. 
5.5. 
Subject and Study Completion 
A completed subject is one who has attended all study visits and has either transitioned to 
an available age appropriate formulation of DTG or ABC/DTG/3TC or has otherwise 
withdrawn from the study (See Section 5.4 for complete details on study withdrawal). 
6. 
STUDY TREATMENT 
6.1. 
Investigational Product and Other Study Treatment 
Investigational Product (IP) is defined as DTG film coated tablets, DTG DT, 
ABC/DTG/3TC immediate release tablets or ABC/DTG/3TC DT. IP for subjects 
transitioning from parent studies P1093 and P2019 will be provided through the study as 
per DTG and ABC/DTG/3TC dosing tables (Appendix 2). Other ARVs will not be 
provided by the study and are not considered part of the study. These other ARVs must 
be supplied locally. 
Single entity DTG, in age appropriate formulations, will be provided to eligible subjects 
transitioning from parent study P1093.  Sites participating in P1093 and this rollover 
study are in the following countries: Botswana, Brazil, Kenya, South Africa, Tanzania, 
Thailand, Uganda, United States and Zimbabwe. 
ABC/DTG/3TC, in age appropriate formulations, will be provided to eligible subjects 
transitioning from parent study P2019.  Sites participating in P2019 and this rollover 
study are in the following countries: Botswana, South Africa, Thailand and the United 
States. 
6.1.1. 
Medical Devices 
• Medical devices are not supplied or manufactured by GSK/ViiV for use in this 
study.  The devices described below were supplied by ViiV/GSK for DAIDS 
sponsored P1093, and P2019 parent studies.  Equivalent medical devices (size and 
material of construction) will be sourced locally by each site for use in this 
205858 study: 
For subjects transitioning from the P1093 parent study: 
• 
Polypropylene dosing cup with graduation marks at 5 mL and 10 mL 
• 
Polypropylene oral Dosing Syringe 5 mL or 10 mL 
For subjects transitioning from the P2019 parent study: 
• 
      Polypropylene Dosing cup with graduation marks at 15 mL, 20 mL,         
25 mL, 30 mL 
• 
Polypropylene Oral Dosing Syringe 25 mL 
 
• Instructions for medical device use are provided within the Study Pharmacy 
Manual.  

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6.2. 
Treatment Assignment 
The IP will be administered in an open-label fashion in this study. Informed consent must 
be obtained prior to any study procedures. 
6.3. 
Planned Dose Adjustments 
Weight in kilograms (Kg) will be measured and recorded at each visit to verify whether 
the subject is receiving the appropriate formulation and dose based on the current dosing 
tables; see Appendix 2. If a subject’s weight change requires a dose adjustment, the dose 
adjustment should be made and the local PPD medical monitor must be notified, although 
team approval for a weight-based dose adjustment is not required. Dose adjustments for 
weight decreases will only be made if the weight decrease persists for 2 consecutive 
study visits. 
6.4. 
Packaging and Labeling 
The contents of the label will be in accordance with all applicable regulatory 
requirements. 
6.5. 
Preparation/Handling/Storage 
• 
Under normal conditions of handling and administration, none of the study IP 
formulations are expected to pose significant safety risks to site staff. A Material 
Safety Data Sheet describing the occupational hazards and recommended 
handling precautions will be provided to site staff if required by local laws or 
will otherwise be available from GSK (on behalf of ViiV Healthcare) upon 
request.  
• 
All formulations must be stored in a secure area under the appropriate physical 
conditions described below. Access to and administration of the IP will be 
limited to the investigator and authorized site staff.  
• 
The investigator or designee should confirm appropriate temperature conditions 
have been maintained during transit for all IP received and any discrepancies are 
reported to PPD and resolved before use of the IP. 
6.5.1. 
DTG Film-Coated Tablets 
DTG film coated tablets are available as 50 mg tablets. Store at 15ºC to 30ºC (59ºF to 
86ºF).  Dispense and store only in the original manufacturer’s container. If provided, the 
desiccant should remain in the bottle. 
No special preparation of study treatment is required. 

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6.5.2. 
DTG Dispersible Tablets 
Dolutegravir 5 mg pediatric DTs are white, round, film-coated tablets for oral 
administration. The tablets are debossed with ‘SV H7S’ on one side and ‘5’ on the 
opposite side. The tablets contain 5.26 mg of dolutegravir sodium which is equivalent to 
5 mg dolutegravir free acid. The tablets are packed into high density polyethylene 
(HDPE) bottles with child resistant closures that include an induction seal. The bottles 
contain a desiccant. Store and dispense in the original package, protect from moisture, 
and keep the bottle tightly closed. Do not remove desiccant. In the study site pharmacy, 
store up to 30°C (86°F). 
Dolutegravir DTs will be dispersed in drinking water for oral administration. Caregivers 
will be instructed to disperse the appropriate number of dispersible tablets in the volume 
of water shown in Table 3. Once dispersed, the medication should be consumed, as soon 
as possible, but no longer than 30 minutes after reconstitution. After the medication is 
consumed, another 5 mL of water should be added to the cup, swirled and provided to the 
subject. If any medicine remains, repeat the instructions above to ensure the subject 
receives the full dose. 
Table 3 
Dispersion Volumes for DTG Dispersible Tablets 
Number of Tablets per Dose 
Dispersion Volume 
1 
5 mL 
2 
3 
4 
10 mL 
5 
6 
6.5.3. 
ABC/DTG/3TC Dispersible Tablets 
ABC 60 mg/DTG 5 mg/3TC 30 mg pediatric dispersible tablets are pale yellow, 
biconvex, oval, film-coated, debossed with ‘SV WTU’ on one side and plain on the 
opposite side. Each tablet contains 70.2 mg abacavir sulfate, which is equivalent to 60 mg 
of abacavir free base; 5.26 mg dolutegravir sodium, which is equivalent to 5 mg of 
dolutegravir free acid; and 30 mg of lamivudine. The tablets are packaged in HDPE 
bottles with child-resistant closures that include an induction seal and a desiccant. Store 
and dispense in the original package, protect from moisture, and keep bottles tightly 
closed. Do not remove desiccant. In the study site pharmacy, store up to 30°C (86°F).  
ABC/DTG/3TC dispersible tablets will be dispersed in water for oral administration. 
Caregivers will be instructed to disperse the appropriate number of dispersible tablets in 
the volume of water shown in Table 4. For children in weight band #3 (14 to less than 20 
kg) or #4 (20 to less than 25 kg) who report poor palatability and/or acceptability, 
caregivers will be provided the option of dispersing the appropriate number of dispersible 
tablets in the volume of water shown in Table 5. Once dispersed, the medication should 

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be consumed, as soon as possible, but no longer than 30 minutes after reconstitution. 
After the medication is consumed, another 15 mL of water should be added to the cup, 
swirled and provided to the subject. If any medicine remains, repeat the instructions 
above to ensure the subject receives the full dose. 
Table 4 
Dispersion Volumes for ABC/DTG/3TC Dispersible Tablets 
Weight Band 
Number of Dispersible 
Tablets per Dose 
Dispersion Volume 
#1 
6 to less than 10 kg 
3 
15 mL 
#2 
10 to less than 14 kg 
4 
20 mL 
#3 
14 to less than 20 kg 
5 
20 mL 
#4 
20 to less than 25 kg 
6 
20 mL 
 
Table 5 
Alternate Dispersion Volumes for ABC/DTG/3TC Dispersible Tablets 
Weight Band 
Number of Dispersible 
Tablets per Dose 
Dispersion Volume 
#1 
6 to less than 10 kg 
3 
15 mL 
#2 
10 to less than 14 kg 
4 
20 mL 
#3 
14 to less than 20 kg 
5 
25 mL 
#4 
20 to less than 25 kg 
6 
30 mL 
 
6.5.4. 
ABC/DTG/3TC Immediate Release (Triumeq) Tablets  
ABC/DTG/3TC immediate release (Triumeq) tablets are purple, biconvex, oval, film-
coated, debossed with “572 Trı” on one side, and plain on the opposite side. Each tablet 
contains 702 mg abacavir sulfate, which is equivalent to 600 mg of abacavir free base; 
52.62 mg dolutegravir sodium, which is equivalent to 50 mg of dolutegravir free acid; 
and 300 mg of lamivudine. Store and dispense in the original package, protect from 
moisture, and keep bottles tightly closed. Do not remove desiccant. In the study site 
pharmacy, store at 25°C (77°F) with excursions between 15° and 30°C (59° to 86°F) 
permitted (See USP Controlled Room Temperature). For any child who is not able to 
swallow whole immediate release tablets, the tablets can be crushed and mixed with a 
liquid or semi-solid food such as applesauce or mashed banana. 

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6.6. 
Product Accountability and Disposal 
The site investigator is responsible for ensuring that all accounting of IP supplies occurs 
in accordance with all local regulatory requirements. This includes accounting for IP 
supplies received, dispensed, and destroyed as necessary. All unused supplies should be 
destroyed by the investigator or designee (e.g., site pharmacist) in accordance with 
national and/or local regulations, with the exception of investigators located in the US 
(See Section 6.6.1). 
NOTE: It is important that IP is dispensed to the subject for whom the supplies 
were requested and approved, and to no other patient; this is required in order to 
ensure compliance with the regulatory requirements. 
6.6.1. 
Special Precautions in the US for Disposal 
Any unused IP should be disposed of in accordance with local requirements; however, 
investigators in the US must return any unused IP according to the Pharmacy Manual. 
6.7. 
Compliance with Study Treatment Administration 
A record of the number of IP tablets dispensed to, and taken by, each subject must be 
maintained and reconciled with study treatment and compliance records. Treatment start 
and stop dates, including dates for treatment delays and/or dose reductions will be 
recorded in the eCRF. 
6.8. 
Management of Study Treatment Overdose 
Any tablet intake exceeding the daily number of IP tablets will be considered an 
overdose. For the purposes of this study, an overdose is not an AE 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 12.7.2) and 
must be reported. The investigator should use clinical judgment in treating overdose, as 
PPD or ViiV Healthcare/GSK are unable to recommend specific treatment. 
6.9. 
Treatment after the End of the Study 
Study drug will be provided until age-appropriate formulations receive local regulatory 
approval and are commercially available, or are available from some other source (e.g. 
government programs, aid programs etc.), or until subjects no longer derive benefit from 
treatment, or until a subject meets a protocol defined criteria for discontinuation, or until 
development of DTG, or ABC/DTG/3TC is terminated.  
Subjects will not receive any additional treatment from ViiV Healthcare after completion 
of the study because all subjects will transition from the study to age appropriate 
available and approved sources of the IP. 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the subject’s medical condition, whether or not ViiV Healthcare/GSK is 
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6.10. 
Meals and Dietary Restrictions 
IP can be administered with or without food. 
6.11. 
Concomitant Medications and Non-Drug Therapies 
Patients should be advised to notify their investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
for interactions between such treatments and IP. 
 
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study. Chemoprophylaxis for HIV-associated 
conditions is encouraged, if appropriate, at the discretion of the subject and their 
physician.  
If HIV-1 RNA levels are being followed per the local SOC, it is highly recommended 
that any vaccine, if necessary, be given during or immediately after a scheduled visit after 
any laboratory tests have been drawn. This is because non-HIV vaccines may cause a 
temporary increase in the level of HIV-1 plasma RNA. 
6.11.1. 
Permitted Medications 
Concomitant medications (prescription and non-prescription) will be permitted during the 
course of the program at the investigator’s discretion (except for prohibited medications 
described in Section 6.11.3) and should be administered only as medically necessary.  
Approved hormonal contraception may be administered with IP. However, the 
investigator should consult local prescribing information for guidance on the use of 
hormonal contraceptives with background ART as some ARVs have clinically significant 
drug interactions with these products. 
IP 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. Iron supplements can be taken with IP provided 
that all are taken together with a meal. Under fasted conditions, IP should be given 2 
hours prior to OR 6 hours after iron supplements. 
Metformin concentrations may be increased by DTG. A dose adjustment of metformin 
should be considered when starting and stopping co-administration of DTG with 
metformin, to maintain glycemic control. 
Clinical monitoring is recommended for subjects taking methadone, as methadone 
maintenance therapy may need to be adjusted in some subjects. 
If any treatments for Coronavirus Disease – 2019 (COVID-19) are planned for a study 
subject, please consult with the study medical monitor to ensure that relevant drug 
interactions are considered and to ensure that continued study participation remains 

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appropriate.  Refer to Section 12.8 ( Appendix 9 COVID-19 Pandemic and Study 
Guidance) for safety reporting requirements and instruction for data capture. 
It is the responsibility of the investigator to check on potential drug-drug interactions 
between background ART and other concomitant therapies, before placing a subject on a 
specific medication. 
6.11.2. 
Concomitant Medications Necessitating DTG Dose Adjustment 
Antiviral Agents 
When constructing a subject’s background ART regimen, other integrase inhibitors (i.e. 
RAL, elvitegravir [EVG]) are prohibited because no PK, safety or efficacy data about co-
administration are available. 
Additionally, the pediatric weight-based once daily dose of DTG must be administered 
twice daily with the following antiviral agents because they have been shown or have 
the potential to decrease plasma DTG concentrations; 
• efavirenz (EFV), 
• nevirapine (NVP), 
• tipranavir/ritonavir (TPV/RTV), 
• and etravirine (ETR) – without boosted protease inhibitors. 
Note: ETR can be dosed at the once daily pediatric dose when co-administered 
with lopinavir/RTV, DRV/RTV or ATV/RTV (these boosted protease inhibitors 
have been shown to counteract ETR enzyme induction). 
Other Agents 
Additionally, the pediatric weight-based once daily dose of DTG must be administered 
twice daily with the following other agents because they have known for potential 
enzyme induction activity; 
• rifampicin –(See Appendix 6, Section 12.6.1.7) 
• carbamazepine 
• phenytoin 
• phenobarbital (barbiturates) 
• St. John’s wort 
6.11.3. 
Prohibited Medications 
When constructing a subject’s background ART regimen, other integrase inhibitors (i.e. 
RAL, elvitegravir [EVG]) are prohibited because no PK, safety or efficacy data about co-
administration are available. 
Dofetilide, pilsicainide or fampridine must NOT be administered concurrently with DTG 
because DTG may inhibit the renal tubular secretion of dofetilide/pilsicainide/fampridine 
resulting in increased dofetilide/pilsicainide/fampridine concentrations and the potential 
for toxicity. 

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6.11.4. 
Additional considerations for ABC/DTG/3TC 
Concomitant administration of a single dose of riociguat (0.5 mg) to HIV patients 
receiving ABC/DTG/3TC FDC led to an approximately three-fold higher riociguat 
AUC(0-∞) when compared to historical riociguat AUC(0-∞) reported in healthy 
participants. Riociguat dose may need to be reduced, consult the riociguat product 
labelling for dosing recommendations. 
The pediatric weight based once daily dose of the single entity DTG (based on weight 
band dosing of ABC/DTG/3TC as noted in Section 12.2.3 Dosing Table) should be 
administered twice daily when ABC/DTG/3TC is co-administered with certain enzyme 
inducing drugs. 
• Liquid medications containing sorbitol or other sugar alcohols (e.g., mannitol, xylitol, 
maltitol, isomalt) should be avoided as these excipients, which are used to sweeten 
pediatric liquid formulations, have been shown to reduce 3TC concentrations [Adkinson, 
2018]. Site investigators should carefully review all liquid concomitant medications 
received by enrolled subjects. If any such medications are not clinically indicated, they 
should be discontinued. Otherwise, they should be switched to a solid dosage form when 
possible or to a liquid formulation that does not contain sorbitol or other sugar alcohols. 
Site investigators should be particularly cognizant of liquid cotrimoxazole formulations, 
which tend to contain high concentrations of sorbitol and are commonly used in HIV-
infected children.  
 
When there is a country specific label with an approved pediatric indication(s), 
please refer to the Local Product Information for Tivicay (DTG) or Triumeq 
(ABC/DTG/3TC) for information on drug:drug interactions. 
 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Table, are essential and required for study conduct. 
This section lists the procedures and parameters of each planned study assessment. The 
exact timing of each assessment is listed in the Time and Events Table Section 7.2.  
The following points must be noted:  
• 
The change in timing or addition of time points for any planned study 
assessments must be documented in a Note to File which is approved by the 
local PPD medical monitor and then archived in the study sponsor and site study 
files, but this will not constitute a protocol amendment.  
• 
The IRB/IEC will be informed of any safety issues that require alteration of the 
safety monitoring scheme or amendment of the Informed Consent Form. 
 

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7.1. 
Study Schematic 
 
 
1. See Penultimate Visit Assessments in Section 7.1.1 
2. Study drug will be provided until age-appropriate formulations receive local 
regulatory approval and are commercially available or are available from some 
other source (e.g. government programs, aid programs etc) or until the subject no 
longer derives benefit from treatment or until a subject meets a protocol defined 
reason for discontinuation or until development of DTG or ABC/DTG/3TC is 
terminated. 

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7.1.1. 
Parent Studies: Penultimate Visit Assessments 
Parent Studies: 
Penultimate Study Visit Assessments (refer to parent 
protocols for details) 
P1093 
P2019 
Penultimate Visit  
Week 180 
Week 36 
Screening Period (approximate) 
Week 
180-Week 
192 
Week 36- 
Week 48 
Clinical Evaluations 
Medical History (review of existing and new conditions) 
X 
X 
Review/update Adverse Events 
X 
X 
Medication History (review of ongoing and new concomitant 
medications) 
X 
X 
Physical Exam 
X 
X 
Laboratory Evaluations 
HIV-1 RNA PCR 
X 
X 
Pregnancy Test (blood or urine as per local SoC) 
X 
X 
CBC with differential and platelets 
N/A 
X 
ALT, AST, total bilirubin, direct bilirubin, creatinine, eGFR 
(bedside Schwartz) 
N/A 
X 
Additional evaluations if clinically indicated 
X 
X 
Dispense IP within Parent Study 
Penultimate Visit: Dispense Parent Study IP 
X 
X 
Informed Consent for 205858 
If subject is benefiting from IP, obtain informed consent for 
205858 
X 
X 
If 205858 informed consent provided: 
Begin Screening phase: Confirm eligibility criteria for 
205858 have been met 
X 
X 

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7.2. 
Time and Events Table 
Table 6 
Time and Events Table 
Event 
Screening 
Visit1 
Day 1 
Visit2 
Every 12 
Weeks 
Withdrawal 
Visit 
Follow-Up 
(post-SAE) 
Visit windows 
 
 
4 Weeks 
4 Weeks 
4 Weeks 
Informed consent 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
Pregnancy test3 
X 
X 
 
X 
 
Adverse events4 
 
X 
X 
X 
X 
Serious adverse events5 
X 
X 
X 
X 
X 
Dispense DTG or 
ABC/DTG/3TC6 
 
X 
X 
 
 
Weight 
X 
X 
X 
X 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
1. The Screening visit corresponds to the penultimate visit of the parent studies. In most cases, this will correspond 
with the Week 180 visit of the P1093 study or the Week 36 visit of the P2019 study. 
2. In most cases, the Day 1 visit will be the same as the final visit for the parent study (i.e. at or beyond Week 192 of 
the P1093 study or at or beyond Week 48 of the P2019 study). 
3. Pregnancy test for females of childbearing potential only. Urine pregnancy test must be used at Day 1 and 
final/withdrawal visit. Remind females of reproductive potential of the need to avoid pregnancy while in study and 
adherence to the study’s contraception requirements. 
At every visit (or some other more frequent interval), pregnancy prevention will be discussed with the subjects, 
including specific counselling, provision of information and advice as needed. Verbal confirmation of the use of an 
acceptable birth control option listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in 
Appendix 3 Section 12.3.1 should be obtained. This discussion should be documented in the subject’s study 
record. 
A pregnancy test should also be performed prior to IP re-administration, when dosing is disrupted for more than 7 
days. 
4. Only AEs leading to treatment discontinuation will be collected. 
5. Only SAEs related to study participation will be collected from the time of informed consent signature and 
administration of study drug at Day 1.  Other SAEs occurring between the time of informed consent signature and 
administration of study drug at Day 1 will be captured in the DAIDS sponsored parent studies.  
6. Subjects transitioning from P1093 parent study will receive age appropriate formulations of DTG; Subjects 
transitioning from P2019 parent study will receive age appropriate formulations of FDC ABC/DTG/3TC. 
 
7.3. 
Screening Visit 
Subjects will sign a new consent specific to this rollover protocol at the Screening visit 
which corresponds to the penultimate visit of the parent studies (approximately Week 180 
for most subjects transitioning from P1093 and Week 36 for most subjects transitioning 
from P2019).  
During the Screening visit, the following are captured in the database (PPD eCRF):  
• Informed Consent. 
• Verification that the subject meets the inclusion/exclusion criteria. 
• The subject’s weight 
• Confirmation of virologic suppression (HIV-1 RNA) (Section 5.1).  

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• A negative pregnancy test result for females of childbearing potential.  
• Any SAE 
• Study treatment, dose and formulation taken by subject. 
Note: On the day of the Screening visit, HIV-1 RNA viral load and pregnancy testing will 
be performed as part of the parent studies. HIV-1 RNA results will be recorded in the 
eCRF and pregnancy test results will be documented in the source notes. 
After eligibility has been verified, the investigator can request a 3-month supply of IP 
from PPD. 
7.4. 
Day 1 Visit 
The following will be obtained at the Day 1 visit and entered into the database (PPD 
eCRF): 
• 
Any modification to DTG or ABC/DTG/3TC dose or formulation at this visit or 
since the last visit. 
• 
Demographic parameters: year of birth, sex, race and ethnicity 
• 
Confirmation that the subject continues to meet inclusion and no exclusion 
criteria. 
• 
Weight 
• 
Pregnancy test results for females of childbearing potential 
• 
Plasma HIV-1 RNA viral load (as collected per local SOC) 
• 
All SAEs 
• 
All AEs leading to treatment discontinuation 
• 
Confirmation that the subject is expected to return for the next quarterly visit. 
The following will be obtained at the Day 1 visit per the local SOC, either directly or 
from the patient’s medical records and retained in the patient’s medical records but 
will not be entered into the database (PPD eCRF): Medical history and physical 
exam (medical/medication/family history will be assessed as related to inclusion 
criteria listed in Section 5); review of changes in concomitant medications and 
background ART; assessment of any adverse events since last parent study visit (all 
SAEs and all AEs that lead to the discontinuation of IP will be captured in the 
database); lymphocyte subsets; lipid profiles and liver chemistry test results.  
7.5. 
Patient Monitoring 
7.5.1. 
Regular Visits (Every 12 Weeks) 
The following will be obtained every 12 weeks and entered into the database (PPD 
eCRF):  
• Any modification to DTG or ABC/DTG/3TC dose or formulation at the current 
visit or since the last visit. 

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• Weight 
• Plasma HIV-1 RNA viral load (as collected per local SOC) 
• Any SAE 
• Any AE leading to treatment discontinuation 
• Confirmation that the subject is expected to return for the next quarterly visit. 
The following assessments are suggested to be performed per local SOC and if 
performed, should be recorded in the investigator’s patient records; these results if 
collected will not be entered into the database (PPD eCRF): Results of any laboratory 
chemistry/hematology, lipid profiles and CD4+ counts per local practice; history and 
physical exam; changes in concomitant medications and background ART; and 
confirmation of effective contraception in females of childbearing potential.   
7.5.2. 
Study Withdrawal/Discontinuation 
Subjects may be withdrawn from the study for any of the reasons outlined in Section 5.4. 
The following assessments are to be performed per local SOC at the withdrawal visit (if 
different from a regular scheduled visit) and will be reported and entered into the 
database (PPD eCRF): 
• Any modification to DTG or ABC/DTG/3TC dose or formulation at the current 
visit or since the last visit. 
• Weight 
• Plasma HIV-1 RNA viral load (as collected per local SOC) 
• Pregnancy status (urine or serum pregnancy test results) 
• Primary reason for study withdrawal: Subjects 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 eCRF. The Study Discontinuation eCRF Form must also be 
completed. Every effort should be made by the investigator to follow-up patients 
who withdraw from the study.  
• Any SAE 
• Any AE leading to treatment discontinuation  
The following assessment are to be performed per local SOC at the withdrawal visit (if 
different from a regular visit) and should be recorded in the investigator’s patient 
records; these results will not be entered into the database (PPD eCRF): Blood 
sample for laboratory assessments per investigator’s judgment for the follow-up of a 
clinically significant abnormality; any changes in concomitant medications and 
background ART; and any  assessments as per SOC according to local practices and 
guidelines (lipid profiles, CD4+, etc.). 
 

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7.6. 
Safety 
At every study visit, the subjects will be asked to provide details of any AEs that have 
occurred. All SAEs, and all AEs that lead to IP discontinuation, will be documented and 
reported by the investigator. Additional information regarding detecting, documenting 
and reporting AEs and SAEs is available in Section 7.6.1. 
The Sponsor recommends local laboratory assessment of hematology and clinical 
chemistry parameters as per local practice and regulatory guidelines when the 
investigator feels there is cause for these assessments. The results of these tests will not 
be collected in the eCRF unless the result(s) are considered to be an SAE by the 
investigator. 
7.6.1. 
Adverse Events (AE) and Serious Adverse Events (SAEs) 
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. All SAEs, and all AEs leading 
to treatment discontinuation, will be reported. 
7.6.1.1. 
Time period and Frequency for collecting AE and SAE information 
• 
All SAEs, and all AEs leading to treatment discontinuation, will be recorded from 
the time a subject provides consent to participate in the study, up to and including 
any Follow-up Visit. 
• 
All SAEs and all clinical or laboratory events leading to discontinuation of IP will 
be recorded and reported to PPD within 24 hours, as indicated in Appendix 7 
Section 12.7.3. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
subjects (after the subject has exited the study). However, if the investigator learns 
of any SAE, including a death, at any time after a subject has been discharged 
from the study, and he/she considers the event reasonably related to IP or study 
participation, the investigator must promptly notify PPD. 
NOTE: The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to PPD are provided in 
Appendix 7.  
7.6.1.2. 
Follow-up of SAEs and AEs leading to discontinuation of IP 
After the initial event report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs or any AEs leading to discontinuation of 
IP (including events meeting liver stopping criteria, as defined in Section 5.4.4) will be 
followed until resolution, until the condition stabilizes, until the event is otherwise 
explained, or until the subject is lost to follow-up (as defined in Section 5.4.2).   

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7.6.1.3. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
The events or outcomes listed in the Centers for Disease Control and Prevention (CDC) 
Classification System for HIV-1 Infections ( Appendix 9 Section 12.8), 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 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 Appendix 7, or 
• 
The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual subject, or 
• 
The investigator considers that there is a reasonable possibility that the event was 
related to treatment with IP 
• 
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 (DRE) 
on the SAE page or the AE leading to IP discontinuation eCRF page, as applicable, 
and report promptly [see Section 12.7.5] to PPD. 
7.6.1.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to PPD of SAEs related to study treatment (even 
for non-interventional post-marketing studies) is essential so that legal obligations and 
ethical responsibilities towards the safety of subjects and the safety of a product under 
clinical investigation are met. PPD must notify ViiV Healthcare of any SAEs within 
24 hours of learning of the event or the next business day if notified during a weekend or 
public holiday.  
ViiV Healthcare has a legal responsibility to ensure that both the local regulatory 
authority and other regulatory agencies are notified about the safety of a product under 
clinical investigation. ViiV Healthcare working with PPD will comply with country 
specific regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/IEC and investigators. Investigators must comply with any additional country 
specific reporting requirements. 
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and ViiV Healthcare or GSK policy, 
as appropriate, and are forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing an SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK on behalf of 

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ViiV Healthcare will file it with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
7.6.2. 
Pregnancy 
7.6.2.1. 
Pregnancy Testing 
Female study subjects of reproductive potential are defined as girls who have reached 
menarche and have not undergone a sterilization procedure (hysterectomy or bilateral 
oophorectomy). Appropriate site personnel should determine the menarche status of 
female study subjects who reach the age of reproductive potential during study and who 
are suspected of having initiated sexual activity. Female study subjects who reach 
reproductive potential during the study and who are sexually active or who are 
considering becoming sexually active should be provided with contraception counselling 
during their participation in the study. Counselling should cover at minimum: the 
potential risks associated with pregnancy (see Section 4.6 for specific risks) during the 
trial; the uncertainty of long-term effects of ART on infant outcome; and avoiding 
pregnancy, safer sexual practices and the proper use of the subjects’ chosen contraceptive 
methods.   
All study subjects must agree to NOT participate in a conception process (e.g. active 
attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). 
Female subjects who are of childbearing potential and who are engaging in sexual 
activity that could lead to pregnancy, must use one of the acceptable birth control options 
listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in 
Appendix 3 Section 12.3.1 until the last dose of IP and completion of the Follow-up Visit 
(4 weeks after the last dose of IP). Condoms are recommended in addition, because their 
appropriate use is the only contraception method effective for preventing HIV-1 
transmission. 
All female subjects of childbearing potential must have a negative pregnancy test at 
Screening and Day 1 to be eligible for enrollment and will be tested again at the time of 
study withdrawal. Pregnancy testing may also be conducted any time during the trial 
when pregnancy is suspected. Additionally, a pregnancy test should also be performed 
prior to IP re-administration, when dosing is disrupted for more than 7 days. Pregnancy 
tests must be performed on urine as per local SOC.  
A pregnancy (intrauterine), regardless of termination status of pregnancy, will result in 
subject withdrawal. 
7.6.2.2. 
Pregnancy Reporting 
Details of all pregnancies in female subjects will be collected over the period starting at 
Screening and ending at the final or Follow-up visit. If a pregnancy is reported then the 
investigator should inform PPD within 24 hours of learning of the pregnancy and should 
follow the procedures outlined in Appendix 3 (Section 12.3.2). 
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 

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ARV products. Additional information and a list of participating manufacturers/licensees 
are available from http://apregistry.com/index.htm. 
7.6.3. 
Physical Exams 
Physical exams should be conducted as part of normal routine clinical care per local SOC 
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). 
AEs are recorded if they are serious or cause withdrawal from treatment. 
7.6.4. 
Vital Signs 
Vital signs should be measured per local SOC practices and may include height, 
temperature, systolic and diastolic blood pressure, respiratory rate and pulse rate.  
A measure of weight must be included in these assessments and will be recorded in the 
eCRF. 
7.6.5. 
Suicidal Risk Monitoring 
Subjects 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 INSTIs, including DTG. Therefore, it may be appropriate, depending on the age of 
the subject, to monitor for suicidality before and during treatment.  
Subjects 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 subjects who experience 
signs of suicidal ideation or behavior. Subjects 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 IP may be required. 
7.6.5.1. 
Possible Suicidality Related Adverse Events 
If any patient experiences a possible suicidality-related adverse event (PSRAE) while 
participating in this study that is considered by the investigator to meet definitions for 
seriousness (Appendix 7, Section 12.7.2), the investigator will collect information using 
the PSRAE eCRF form in addition to the SAE eCRF form. A PSRAE 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 PPD within 
1 week of the investigator diagnosing a possible suicidality-related AE, if the PSRAE is a 
SAE or if the PSRAE leads to treatment discontinuation. In the case of SAE, the SAE 
eCRF should be completed and submitted within 24 hours of diagnosing a possible 
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8. 
DATA MANAGEMENT 
For this study, minimal patient data (i.e., demographics, SAEs and any AE leading to 
withdrawal/discontinuation of DTG) will be entered into eCRFs, transmitted 
electronically to PPD and combined with data provided from other sources in a validated 
data system. 
Management of clinical data will be performed in accordance with applicable PPD 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
errors and inconsistencies in the data.  
SAE terms will be coded using the Medical Dictionary for Regulatory Activities. In all 
cases, patient initials will not be collected or transmitted to PPD according to PPD policy. 
9. 
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES 
9.1. 
Hypotheses 
This is an open-label, rollover study. No formal hypothesis testing will be performed. The 
objectives of this study will be supported through evaluation of SAEs, which will be 
categorized according to the DAIDS Table for grading pediatric AEs (Appendix 10, 
Section 12.10). Data will provide only descriptive information on safety and tolerability. 
9.2. 
Sample Size Considerations 
Based on the design of the parent studies, a maximum of 300 pediatric subjects with HIV 
could enroll in this study.  
9.3. 
Data Analysis Considerations 
9.3.1. 
Analysis Populations 
The safety population will comprise all subjects who have received at least one dose of IP 
once enrolled in this study. This population will be used for analyses of safety data. 
9.3.2. 
Interim Analysis 
No interim analysis is planned, however, data may be pulled periodically to support 
registrations and/or safety analyses updates. 
9.4. 
Key Elements of Analysis Plan 
SAEs will be summarized and categorized by the DAIDS toxicity scale (Appendix 10, 
Section 12.10). The SAE analyses will take place upon closure of the protocol; however, 
data cuts and analyses may be conducted as necessary in order to support regulatory 
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All summaries will be presented by the parent study. Descriptive listings will be 
provided. 
10. 
STUDY GOVERNANCE CONSIDERATIONS 
10.1. 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted by PPD on www.clinicaltrials.gov 
before enrollment of subjects begins. 
10.2. 
Regulatory and Ethical Considerations, Including the 
Informed Consent Process 
Prior to initiation of a site, PPD on behalf of ViiV Healthcare, will obtain favorable 
opinion/approval from the appropriate regulatory agency to conduct the study in 
accordance with International Conference on Harmonisation (ICH) Good Clinical 
Practice (GCP) and applicable country-specific regulatory requirements. 
The study will be conducted in accordance with all applicable regulatory requirements, 
and with ViiV Healthcare/GSK policy, as appropriate. 
The study will also be conducted in accordance with ICH GCP, all applicable subject 
privacy requirements, and the guiding principles of the current version of the Declaration 
of Helsinki. This includes, but is not limited to, the following: 
• 
IRB/IEC review and favourable opinion/approval of the study protocol and 
amendments as applicable 
• 
Obtaining signed informed consent 
• 
Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB/IEC) 
• 
ViiV Healthcare/GSK will provide full details of the above procedures, either 
verbally, in writing, or both. 
• 
Written informed consent for study participation will be obtained before any 
study-specific procedures are performed. Since the Screening visit overlaps with 
the Week 180 visit in P1093 or the Week 36 visit in P2019 (or later visits) of the 
parent studies, the informed consent process will be conducted before any study 
assessment activities begin.  
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 subject (or parents or legal guardians of subjects who 
cannot consent for themselves, such as those below the legal age). The subject’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 

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to be followed, and the risks and benefits of participation. A copy of the consent form 
will be given to the subject (or parent or legal guardian).  
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 
infant, reflective of applicable IRB/IEC guidance for conduct of human subjects research 
within the context of available local law, regulation, or government policy. 
10.2.1. 
Children in care 
DAIDS is a sponsor of the parent studies. As per DAIDS policy, children in care (i.e 
children who are wards of State or any other agency, institution or entity) may be 
enrolled in the parent studies. Under ViiV Healthcare sponsorship, the recruitment of 
children in care is only permitted with Chief Medical Officer (CMO) approval. As post 
study drug access and continuity of care for all children and adolescents in the parent 
studies is provided through 205858 (ViiV Healthcare sponsored study), the ViiV CMO 
has approved the transition of eligible children in care enrolled in the parent studies into 
the 205858 study. Transition of eligible children in care will ensure continuity of care and 
access to IP until age appropriate formulations receive local regulatory approval and are 
commercially available or are available from another source (e.g. government programs, 
aid programs, assistance programs), or the subject no longer derives benefit from IP or 
meets a protocol defined reason for discontinuation. 
Sites must establish and maintain written procedures describing local standards for 
identifying who may serve as legal guardian for a clinical research subject and how 
guardianship will be recognized within the context of available IRB/IEC guidance, local 
law, regulation and/or government policy.  Evidence of guardianship should be 
documented at study entry and during the study if a change in guardianship occurs. 
• If a subject is a child in care (ward of state or any other agency, institution or 
entity) at the time of screening, the site investigator must notify the Study Medical 
Monitor prior to enrollment. Documentation of appropriate guardianship (within 
the context of available IRB/EC guidance, local law, regulation and/or 
government policy) must be provided and confirmed by the Study Medical 
Monitor prior to enrollment.  
• If a change in guardianship occurs and the subject becomes a child in care (ward 
of state or any other agency, institution or entity) during the study, the site 
investigator must notify the Study Medical Monitor immediately. The ViiV CMO 
will review cases and determine if subjects may continue to participate in the 
study. 

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• Child in care status at the time of enrollment will be entered into the eCRF for all 
subjects enrolled in the study. Changes in guardianship resulting in a subject 
becoming a child in care during study conduct will also be entered into the eCRF. 
10.3. 
Quality Control (Study Monitoring) 
• 
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 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. 
• 
Data reported in the eCRFs that are transcribed from source documents (i.e. 
documentation from the parent study) must be consistent with the source 
documents or 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. 
PPD will monitor the study and site activity to verify that the: 
• 
Data are authentic, accurate, and complete. 
• 
Safety and rights of subjects are being protected. 
• 
Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents. 
10.4. 
Quality Assurance 
• 
To ensure compliance with GCP and all applicable regulatory requirements, 
ViiV Healthcare/GSK or its designee may conduct a quality assurance assessment 
and/or audit of the site records, and the regulatory agencies may conduct a 
regulatory inspection at any time during or after completion of the study.  
• 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss 
the conduct of the study, any findings/relevant issues and to implement any 
corrective and/or preventative actions to address any findings/issues identified. 
10.5. 
Study and Site Closure 
• 
Participation of a subject in study 205858 will end when an age appropriate 
formulation of IP becomes available to the subject, unless the study is terminated 
early. Unless terminated early, this study will be considered completed after the 
last subject completes the last study-related clinic visit or assessment.  

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• 
Upon completion or premature discontinuation of the study, PPD will remotely 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and ViiV Healthcare/GSK 
Standard Operating Procedures, as appropriate. 
• 
ViiV Healthcare/GSK reserves the right to temporarily suspend or prematurely 
discontinue this study at any time for reasons including, but not limited to, safety 
or ethical issues or severe non-compliance. For multicenter studies, this can occur 
at one or more or at all sites.   
• 
If ViiV Healthcare/GSK or its designee determines such action is needed, 
ViiV Healthcare/GSK will discuss the reasons for taking such action with the 
investigator or the head of the medical institution (where applicable). When 
feasible, ViiV Healthcare/GSK will provide advance notification to the 
investigator or the head of the medical institution, where applicable, of the 
impending action. 
• 
If the study is suspended or prematurely discontinued for safety reasons, 
ViiV Healthcare/GSK will promptly inform all investigators, heads of the medical 
institutions (where applicable) and/or institution(s) conducting the study. 
ViiV Healthcare/GSK will also promptly inform the relevant regulatory 
authorities of the suspension or premature discontinuation of the study and the 
reason(s) for the action.   
• 
If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation. 
10.6. 
Records Retention 
• 
Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records, including the 
eCRFs (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. 

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• 
ViiV Healthcare/GSK will inform the investigator of the time period for retaining 
these records to comply with all applicable regulatory requirements.  The 
minimum retention time will meet the strictest standard applicable to that site for 
the study, as dictated by any institutional requirements or local laws or 
regulations, ViiV Healthcare/GSK standards/procedures, and/or institutional 
requirements, as appropriate.   
• 
The investigator must notify ViiV Healthcare/GSK of any changes in the archival 
arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site. 
• 
eCRFs (including queries and audit trails) will be retained by ViiV 
Healthcare/GSK, and copies will be sent to the investigator to maintain as the 
investigator copy 
10.7. 
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication 
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 study site or other mutually-
agreeable location. 
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, as appropriate. 

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11. 
REFERENCES 
Adkinson K. WA, Lou Y., Zhang Y., Eld A., Perger T., Vangerow H., Hayward K., 
Shaefer M., McCoig C, Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine 
Oral Solution in Adults: An Open-Label, Randomized Study. Clinical pharmacology and 
therapeutics. 2018;103(3):6. 
Andrade RJ, Robles M, Lucena MI.  Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opinion on Drug Safety. 2009; 8:709-714. 
European AIDS Clinical Society (EACS) [internet]. Guidelines for the treatment of HIV-
positive adults in Europe; 2018 [Cited March 20, 2019]. Available from: 
http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdf 
Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, et al. editors. 
Contraceptive Technology. 20th edition.  Atlanta, Georgia: Ardent Media, Inc., 2011: 50.  
Table 3-2. 
International Conference on Harmonization of Technical Requirements for Registration 
of Pharmaceuticals For Human Use. ICH Harmonized Tripartite Guideline. Clinical 
safety data management: Definitions and standards for expedited reporting. ICH E2A. 
1994 
James L, Letzig L, Simpson P, Capparelli E, Roberts D, Hinson J, et al. Pharmacokinetics 
of Acetaminophen-Adduct in Adults with Acetaminophen Overdose and Acute Liver 
Failure. Drug Metab Dispos 2009; 37:1779-1784. 
Mallal S, Phillips E, Carosi G, et. Al. HLA-B*5701 screening for abacavir 
hypersensitivity. New England Journal of Medicine. 2008;358:568-79. 
Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, 
efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, 
administered with efavirenz, in antiretroviral-naïve, HIV-1-infected adults: 48-week 
results from the ASSERT study. J Acquir Immune Defic Syndr. 2010; 55(1):49-57. 
Ruel T, Acosta E, Singh R, and the P1093 Team. PK and 4-week Outcomes of 
Dolutegravir Dispersible Tablets in HIV-1 Infected Children.  CROI 2019, Boston, MA, 
USA. 
Ruel T, Acosta E, Singh R, and the P1093 Team. Pharmacokinetic and 4-week 
safety/efficacy of dolutegravir (S/GSK1349572) dispersible tablets in HIV-infected 
children aged 4 weeks to < 6 years: results from IMPAACT P1093. Abstract LBPEB023 
22nd International AIDS Conference, 23-27 July 2018, Amsterdam, The Netherlands. 
Squires KE, Young B, DeJesus E, et al. Safety and efficacy of a 36-week induction 
regimen of abacavir/lamivudine and ritonavir-boosted atazanavir in HIV-infected 
patients. HIV Clin Trials. 2010; 11(2):69-79. 
TIVICAY, EMA Summary of Product Characteristics (October 2015) 

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US Department of Health and Human Services (DHHSa) [Internet]. Panel on 
Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents; 2019 [cited March 20, 
2019]. Available from: 
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf  
US Department of Health and Human Services (DHHSb) [Internet]. Panel on 
Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines 
for the Use of Antiretroviral Agents in Pediatric HIV Infection; 2019 [cited March 20, 
2019]. Available from: 
https://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf  
Viani RM, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, et al. Safety, 
Pharmacokinetics and Efficacy of Dolutegravir in Treatment-Experienced HIV-1 Infected 
Adolescents: 48-Week Results from IMPAACT P1093. The Pediatric infectious disease 
journal. 2015; Publish Ahead of Print. 
World Health Organization (WHO) [internet]. Updated recommendations on first-line 
and second-line antiretroviral regimens and post-exposure prophylaxis and 
recommendations on early infant diagnosis of HIV; 2018 [Cited March 20, 2019]. 
Available from: https://www.who.int/hiv/pub/guidelines/ARV2018update/en/Appendices 

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12. 
APPENDICES 
12.1. 
Appendix 1 – Abbreviations and Trademarks 
Abbreviations 
3TC 
lamivudine 
ABC 
abacavir 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine aminotransferase 
ART 
Antiretroviral therapy 
ARV 
Antiretroviral 
AST 
Aspartate aminotransferase 
ATV 
Atazanavir 
CD4+ 
Helper-inducer T-lymphocyte having surface antigen CD4 (cluster of 
differentiation 4) 
CDC 
Centers for Disease Control and Prevention 
COVID-19 
Coronavirus Disease - 2019 
CMO 
Chief Medical Officer 
eCRF 
Electronic case report form 
c/mL 
Copies per millilitre 
DAIDS 
Division of AIDS (United States) 
DILI 
Drug induced liver injury 
DNA 
Deoxyribonucleic acid 
DRV 
darunavir 
DT 
Dispersible tablet 
DTG 
Tivicay (dolutegravir) 
EFV 
efavirenz 
EMA 
European Medicines Agency 
ETR 
etravirine 
EU 
European Union 
EVG 
elvitegravir 
FDA 
Food and Drug Administration 
FDC 
Fixed dose combination 
FPV 
fosamprenavir 
FTC 
emtricitabine 
GCP 
Good Clinical Practice 
GCSP 
Global Clinical Safety and Pharmacovigilance 
GSK 
GlaxoSmithKline 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HDPE 
High Density Polyethylene 
HIV 
Human immunodeficiency virus 
HIV-1 
Human immunodeficiency virus type 1 
HLA 
Human leukocyte antigen 

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HSR 
Hypersensitivity reaction 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMPAACT 
International Maternal Pediatric Adolescent AIDS Clinical Trials 
(Network) 
IgM 
Immunoglobulin M 
INR 
International Normalized Ratio 
INSTI 
Integrase strand transfer inhibitor 
IP 
Investigational product 
IRB 
Institutional Review Board 
kg 
Kilogram 
LAR 
Legally authorized representative 
LOC 
Local operating company 
mg 
Milligrams 
mL 
Millilitre 
NIAID 
National Institute of Allergy and Infectious Diseases 
NICHD 
National Institute of Child Health and Human Development 
NNRTI 
Non-nucleoside reverse transcriptase inhibitor 
NRTI 
Nucleoside reverse transcriptase inhibitor 
NVP 
nevirapine 
PI 
Principal investigator 
PK 
Pharmacokinetics 
PMTCT 
Prevention of mother-to-child transmission 
PPD 
Pharmaceutical Product Development 
RNA 
Ribonucleic acid 
RTV 
ritonavir 
SAE 
Serious Adverse Event 
SJS 
Stevens-Johnson Syndrome 
SOC 
Standard of Care 
TB 
Tuberculosis 
TDF 
tenofovir disoproxil fumarate 
TEN 
Toxic Epidermal Necrolysis 
TPV 
tipranavir 
UK 
United Kingdom 
ULN 
Upper Limit of Normal 
US 
United States (of America) 
VF 
Virological Failure 
VSLC 
ViiV Healthcare Safety and Labelling Committee 

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Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
Tivicay 
 
None 
Tivicay PD 
 
 
Triumeq 
 
 

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12.2. 
Appendix 2 – Dosing Tables 
The dosing tables provided below align to those used in the P1093, and P2019 parent 
studies.   
As new data become available, subjects in this study may be able to switch to different 
DTG (and/or ABC and 3TC) doses (e.g. new doses to receive local licensure or doses 
recommended in local treatment guidelines, if updated) than outlined below.  A change 
from the dosing approach used in the parent study must be discussed and agreed with the 
ViiV Medical Monitor. 
If new dosing for either DTG or ABC/DTG/3TC is approved during the conduct of 
this study, subjects will be allowed to switch to these doses as allowed by local 
practice.  
12.2.1. 
Tivicay DTG Film Coated Tablets 
• The DTG 50 mg film coated tablet is approved for use in children weighing 20 kg 
and above.  
• Subjects using the DTG 30 mg dispersible tablet dose may switch to the DTG 
50 mg film coated tablet as appropriate (i.e., Investigator determines the 
participant is able to swallow the tablet and use is appropriate). 
12.2.2. 
DTG Dosing Table for subjects transitioning from parent study 
P1093 
Table R – Dispersible Tablets – with maximum dose of 30 mg* 
Age 
Weight Band (kg) Dose (mg) Dose (mg/kg)  
 
 
 
low weight 
high weight  
≥ 4 weeks to < 6 
months of age 
3 - <6 
5  
1.67 
0.83  
6 - <10 
10  
1.67 
1.00  
≥ 6 months of age 
3- < 6  
10 
3.33 
1.67 
6- <10 
15 
2.50 
1.50 
10 - <14  
20 
2.00 
1.43 
14 - <20 
25 
1.79 
1.25 
≥20 
30 
1.50 
 
*Subjects who reach the 30 mg dose may be able to switch to the film coated 50 mg tablet. 

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12.2.3. 
ABC/DTG/3TC Dosing table for subjects transitioning from parent 
study P2019 
ABC/DTG/3TC tablets (60 mg/5 mg/30 mg dispersible tablets or 600 mg/50 mg/300 mg 
immediate release [Triumeq] tablets) will be taken once daily, generally with or without 
food, at doses specified below: 
 
Weight Band 
Study Drug Formulation 
(Daily Dose of ABC/DTG/3TC) 
#1 
6 to less than 10 kg 
3 dispersible tablets 
(180/15/90 mg) 
#2 
10 to less than 14 kg 
4 dispersible tablets 
(240/20/120 mg) 
#3 
14 to less than 20 kg 
5 dispersible tablets 
(300/25/150 mg) 
#4 
20 to less than 25 kg 
6 dispersible tablets 
(360/30/180 mg) 
#5 
25 kg or greater 
1 immediate release tablet 
(600/50/300 mg) 

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12.3. 
Appendix 3 – Pregnancy 
12.3.1. 
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 subjects 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. 
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 sterilization with documentation of azoospermia prior to the female 
subject's entry into the study, and this male is the sole partner for that subject 
[Hatcher, 2011]. The documentation on male sterility can come from the site 
personnel’s: review of subject’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 subjects understand how to properly use these methods of contraception. 
12.3.2. 
Collection of Pregnancy Information 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study 
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a subject's pregnancy. 
• 
Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on mother and infant, which will be 
forwarded to GSK.  Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
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 SAE or an 
AEs leading to discontinuation of IP where applicable. 
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
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• 
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 GSK 
as described in Section 12.7.5. While the investigator is not obligated to actively 
seek this information in former study subjects, he or she may learn of an SAE 
through spontaneous reporting. 
 
Any female subject who becomes pregnant while participating will be withdrawn 
from the study. 
 
 
 
 

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12.4. 
Appendix 4 – Liver Safety – Study Treatment Restart 
Guidelines 
If a causal relationship between the liver event and IP cannot be ruled out, then IP must 
be permanently discontinued and the subject not rechallenged.  
12.4.1. 
Drug Restart Following Transient Resolving Liver Events Not 
Related to Study Drug 
Restart can be considered when liver chemistries improve to within 1.5x baseline and 
ALT<3xULN) where: 
• Liver chemistries have a clear underlying cause other than drug-induced liver 
injury (e.g biliary obstruction, pancreatic events, hypotension, acute viral 
hepatitis).  Furthermore, there should be no evidence of alcoholic hepatitis or 
hypersensitivity, and the drug should not be associated with HLA markers of liver 
injury. 
• If restart of ABC/DTG/3TC is being considered, then the subject must be HLA-
B*5701 negative (even in countries where HLA-B*5701 screening is not 
considered standard of care). 
• The subject is receiving compelling benefit and benefit of drug restart exceeds 
risk 
• Approval from the ViiV Healthcare Safety and Labelling Committee (VSLC) and 
Ethics Committee or Institutional Review Board for the drug restart has been 
obtained. 
• The subject has been provided with a clear description of the possible benefits and 
risks of drug restart, including the possibility of recurrent, more severe liver injury 
or death. 
• The subject has also provided signed informed consent specifically for the restart.  
Documentation of informed consent must be recorded in the study file. 
• Following drug restart, it is recommended that the Subject return to the clinic 
once a week for liver chemistry tests for one month or for as long as clinically 
indicated and then laboratory monitoring may resume.  If protocol defined 
stopping criteria for liver chemistry elevations are met, study drug must be 
stopped. 
 

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12.5. 
Appendix 5 – Liver Safety – Checklist for Drug Restart 
Approval or Refusal 
“Drug restart” after discontinuation of Study Drug due to Liver Stopping Criteria (as 
defined in the protocol), can only be approved by the ViiV Safety and Labelling 
Committee (VSLC) for transient, defined non-drug-induced liver injury with no 
evidence of: 
• immunoallergic injury/HLA association with injury 
• drug-induced liver injury 
• alcoholic hepatitis 
Investigators MUST: 
1. Hold study drug while labs and evaluations are completed to assess diagnosis, and not 
restart until “Drug restart” has been approved by the VSLC. 
2. Complete the table below and submit to the VSLC. The Liver Event case report form 
should already have been submitted to PPD, along with liver imaging and/or liver 
biopsy case report forms and/or SAE case report form where applicable. Where 
restart of ABC/DTG/3TC is being considered, provide documentation verifying 
HLA-B*5701 status. 
Subject Number: 
Yes 
No 
Have liver chemistries improve to within 1.5x baseline and ALT<3xULN? 
 
 
Was subject’s HIV infection stable or improving on Study Drug? 
 
 
Were any of the following high-risk factors included in the initial liver injury event? 
(Do not restart if ‘Yes’ for any one of the following high-risk factors): 
• fever, rash, eosinophilia, or hypersensitivity  
 
 
• drug-induced liver injury  
 
 
• alcoholic hepatitis (aspartate aminotransferase>ALT, typically <10xULN) 
 
 
• Study Drug (other than ABC) has an HLA genetic marker associated with 
liver injury 
 
 
For restart of TRIUMEQ, or any other abacavir- containing Study Drug, 
the subject MUST be HLA-B*5701 negative1   Specify HLA-B*5701 status2: 
 
1. In countries/regions where HLA-B*5701 pre-therapy screening is not considered standard 
of care, subjects stopping abacavir- containing study drug due to Liver Stopping Criteria 
MUST be tested and found to be negative for the HLA-B*5701 allele before abacavir- 
containing Study Drug can be re-started. 
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12.6. 
Appendix 6 – 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 10, Section 12.10). 
Additional information regarding detecting, documenting and reporting AEs and SAEs 
are available in Section 12.7, Appendix 7. 
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 subject 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 subject’s eCRF. 
Note: For subjects receiving an ABC-containing product as part of the background 
regimen, in the event of a discontinuation of ABC for any reason, reinitiation of this drug 
should be undertaken with caution. The investigator should obtain a complete history of 
the events surrounding the discontinuation of the ABC-containing product, evaluate for 
the possibility of a clinically suspected HSR, and initiate subject management as outlined 
in the Local Country Prescribing Information, regardless of a subject’s HLA-B*5701 
status. Screening for the presence of HLA-B*5701 is recommended prior to reinitiating 
treatment with ABC-containing products in subjects of unknown HLA-B*5701 status 
who have previously tolerated ABC. 
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 creatine 
phosphokinase (CPK) elevation)  that are considered to be related or possibly related to 
study treatment see Section 12.6.1. Specific Toxicities/Adverse Event Management. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Subjects who develop a Grade 1 or Grade 2 AE or toxicity may continue study treatment 
at the discretion of the investigator.  Subjects who choose to withdraw from the study due 
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Grade 3 Toxicity/Adverse Event 
Subjects 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. 
Subjects 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.  
Should the same Grade 3 AE recur within 28 days in the same subject, study treatment 
should be permanently discontinued and the subject withdrawn from study.  Subjects 
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. 
Subjects 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 12.6.1.6 and rash in Section 
12.6.1.5 respectively. 
Grade 4 Toxicity/Adverse Event 
Subjects 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.  Subjects should be rechecked each week until the AE returns to Grade 
2. 
Subjects 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. 
Subjects 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 12.6.1.6. An in-clinic Follow-up visit will be conducted approximately 4 weeks 
after the last dose of IP for subjects with ongoing AEs, and SAEs and also any laboratory 
abnormalities that are considered to be AEs or potentially harmful to the subject, at the 
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12.6.1. 
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.  
Subjects who permanently discontinue study treatment for reasons of toxicity should be 
followed weekly until resolution of the AE and be encouraged to complete the 
withdrawal and follow-up study evaluations as noted in Appendix 7, Section 12.7.3. 
12.6.1.1. 
Decline in Renal Function 
Refer to Section 5.4.3 Management of Renal Toxicity. 
12.6.1.2. Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event etiology during administration of study drug and the follow-up 
period. For a complete listing of stopping and follow-up criteria refer to Section 5.4.4 and 
Appendix 4 Section 12.4. 
12.6.1.3. Restarting Study Drug 
Refer to Appendix 4 Section 12.4 for details on drug restart following transient resolving 
liver events not related to study treatment. 
12.6.1.4. Allergic reaction 
Subjects may continue study drug for Grade 1 or 2 allergic reactions at the discretion of 
the investigator.  The subject should be advised to contact the investigator immediately if 
there is any worsening of symptoms or if further systemic signs or symptoms develop.  
Antihistamines, topical corticosteroids, or antipruritic agents may be prescribed.  
Subjects with Grade 3 allergic reactions that are considered to be possibly or probably 
related to the study drug should permanently discontinue study treatment and the subject 
should be withdrawn from the study.  Subjects should be treated as clinically appropriate 
and followed until resolution of the AE. 
Subjects receiving ABC as part of their NRTI background regimen should be evaluated 
for the possibility of a clinically suspected ABC hypersensitivity reaction (HSR) and 
managed appropriately as outlined in the local prescribing information. 
12.6.1.5. 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 2 to 3 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 
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Subjects with an isolated Grade 1 rash may continue study drug at the investigator’s 
discretion.  The subject should be advised to contact the investigator immediately if there 
is any worsening of the rash, if any systemic signs or symptoms appear, or if mucosal 
involvement develops. 
Subjects 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 subject should be advised to contact the physician 
immediately if rash fails to resolve (after more than 2 weeks), if there is any worsening of 
the rash, if any systemic signs or allergic symptoms develop, or if mucosal involvement 
develops. 
Subjects 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 etiology of the rash has been definitively diagnosed as NOT 
attributable to study drug (see below), and the subject should be withdrawn from the 
study.  Subjects 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, Appendix 10, Section 12.10). 
However, if the etiology of the rash has been definitively diagnosed as being unrelated to 
IP 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. Subjects 
receiving ABC should be evaluated for the possibility of a clinically suspected ABC HSR 
and managed appropriately as outlined in the local prescribing information. 
12.6.1.6. Hypertriglyceridemia/Hypercholesterolemia 
If monitored per local SOC, the Sponsor recommends that samples for lipid 
measurements be obtained in a fasted state every 12 weeks. Subjects who experience 
asymptomatic triglyceride or cholesterol elevations may continue to receive study drug. 
12.6.1.7. Co-infection with TB 
Subjects who are already enrolled and are on therapy who become exposed to 
tuberculosis (TB), and subsequently require an anti-TB treatment that includes the use of 
rifampin are permitted to continue in the study if their ART options are compatible with 
co-administration of rifampin. Management of these subjects is as follows: 
• 
When administration of the rifampin-containing anti-TB treatment begins, 
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based on weight). DTG study treatment duration continues to be administered 
twice daily while subject is on the rifampin containing anti-TB therapy. 
• 
It is estimated the subject will be on anti-TB treatment for approximately 24 
weeks. Approximately two weeks after discontinuation of the rifampin containing 
anti-TB therapy, the subject’s DTG dose will revert back to once daily 
administration unless on EFV, ETR, NVP, or TPV/RTV. 
Subjects who roll-over from the parent study during the course of rifampicin containing 
therapy should continue their DTG dose twice daily. Approximately two weeks after 
discontinuation of the rifampin containing anti-TB therapy, the subject’s DTG dose will 
revert back to once daily administration unless on EFV, fosamprenavir (FPV)/RTV, or 
TPV/RTV. 
For subjects from the P2019 parent study who are taking FDC ABC/DTG/3TC, it is 
generally expected that the frequency of DTG dosing will be increased from once daily to 
twice daily, using a single agent formulation of DTG for the second daily dose; doses and 
formulations to be provided are shown in Table 5. Approximately two weeks after 
discontinuation of rifampin treatment, the study drug regimen corresponding to the 
child’s current weight should be resumed. 
Table 7 
Second Daily Dose of DTG for Children in P2019 Who Require 
Rifampin-Containing TB Treatment  
 
Weight Band 
Second Daily Dose of DTG 
#1 
6 to less than 10 kg  
DTG 15 mg (three 5 mg dispersible tablets) 
#2 
10 to less than 14 kg  
DTG 20 mg (four 5 mg dispersible tablets) 
#3 
14 to less than 20 kg  
DTG 25 mg (five 5 mg dispersible tablets) 
#4 
20 to less than 25 kg  
DTG 30 mg (six 5 mg dispersible tablets) OR 
DTG 50 mg (one film coated tablet) 
#5 
25 kg or greater  
DTG 50 mg (one film coated tablet) 
 
12.6.1.8. Subjects Co-infected with Hepatitis B Virus (HBV) 
Investigators should consult current treatment guidelines (e.g. [DHHSa, 2019; DHHSb, 
2019]) when considering choice of NRTIs for subjects with chronic HBV infection 
(HBsAg positive OR anti-HBc positive with HBV DNA present).   
In addition, clinical trial and marketed use of 3TC, FTC and TDF have shown that some 
subjects with chronic HBV disease may experience clinical or laboratory evidence of 
recurrent hepatitis upon discontinuation of 3TC, FTC or TDF, which may have more 
severe consequences in subjects with decompensated liver disease. Subjects with HBV 
co-infection should be advised against self-discontinuation of any medications with anti-
HBV activity. If 3TC, FTC or TDF is discontinued in subjects co-infected with HBV, 
periodic monitoring of both liver chemistry tests and markers of HBV replication should 
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Entecavir and telbivudine are permitted, in appropriate clinical situations, for treatment of 
HBV (e.g. prior intolerance or viral resistance to TDF, viral resistance to 3TC/FTC) after 
discussion and agreement between the investigator and the medical monitor.   
12.6.1.9. ABC Hypersensitivity 
Both ABC and DTG are associated with a risk for a hypersensitivity reaction and share 
some common features such as fever and/or rash with other symptoms indicating multi-
organ involvement. Clinically it is not possible to determine whether a hypersensitivity 
reaction with ABC/DTG/3TC fixed dose combination is caused by ABC or DTG. 
Hypersensitivity reactions have been observed more commonly with ABC, some of 
which have been life-threatening, and in rare cases fatal, when not managed 
appropriately. More detailed clinical descriptions of these reactions are included in the 
ABC/DTG/3TC Investigator Brochure and Local Prescribing Information. 
The risk for ABC hypersensitivity reactions to occur is significantly increased for patients 
who test positive for the HLA-B*5701 allele. However, ABC hypersensitivity reactions 
have been reported at a lower frequency in patients who do not carry this allele. In the 
prospective study CNA106030 (PREDICT-1), the use of pre-therapy screening for the 
presence of HLA-B*5701 and subsequently avoiding ABC in HLA-B*5701 positive 
patients, significantly reduced the incidence of clinically suspected ABC hypersensitivity 
reactions from 7.8% (66 of 847) to 3.4% (27 of 803) (p<0.0001) [Mallal, 2008]. In 
clinical studies EPZ108859 (ARIES) and CNA109586 (ASSERT), 0.8% (4/515) and 
3.1% (6/192) of subjects who were HLA-B*5701 negative and who received ABC 
developed a clinically suspected ABC hypersensitivity reaction, respectively [Post, 2010, 
Squires, 2010].  
The following should be adhered to in the management of subjects presenting with signs 
and symptoms suggesting a possible hypersensitivity reaction: 
• In any subject treated with ABC/DTG/3TC, the clinical diagnosis of a suspected 
hypersensitivity reaction must remain the basis of clinical decision making. 
• ABC/DTG/3TC must be stopped without delay, even in the absence of the HLA-
B*5701 allele, if a hypersensitivity reaction is suspected. Delay in stopping 
treatment with ABC/DTG/3TC after the onset of hypersensitivity may result in a 
life-threatening reaction. Clinical status including liver aminotransferases and 
bilirubin should be monitored.  
• Subjects who have experienced a hypersensitivity reaction should be instructed to 
return their remaining ABC/DTG/3TC tablets to the site, in order to avoid 
restarting ABC. 
• After stopping treatment with ABC/DTG/3TC for reasons of a suspected 
hypersensitivity reaction, ABC/DTG/3TC or any other medicinal product 
containing ABC or DTG must never be re-initiated. 
• Restarting ABC-containing products following a suspected ABC hypersensitivity 
reaction can result in a prompt return of symptoms within hours and may include 
life-threatening hypotension and death. 

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• If a hypersensitivity reaction is ruled out, Subjects may restart ABC/DTG/3TC. 
Rarely, patients who have stopped ABC for reasons other than symptoms of a 
hypersensitivity reaction have also experienced life-threatening reactions within 
hours of re- initiating ABC therapy. Subjects must be made aware that a 
hypersensitivity reaction can occur with reintroduction of ABC/DTG/3TC or any 
other medicinal product containing ABC and that reintroduction of 
ABC/DTG/3TC or any other medicinal product containing ABC should be 
undertaken only if medical care can be readily accessed. 
12.6.1.9.1. Reporting of ABC Hypersensitivity Reactions 
If a clinically suspected case of a hypersensitivity reaction to ABC meets one of the ICH 
E2A (ICH E2A, 1994) definitions of seriousness listed in Section 12.7.2 then, in addition 
to reporting the case as a serious adverse event, the ABC hypersensitivity reaction case 
report form should also be completed within one week of the onset of the hypersensitivity 
reaction and sent to the Sponsor. 
In the event of a discontinuation of ABC/DTG/3TC for any reason, re-initiation of this 
drug should be undertaken with caution. The investigator must obtain a complete history 
of the events surrounding the discontinuation of ABC/DTG/3TC, evaluate for the 
possibility of a clinically suspected hypersensitivity reaction, and initiate subject 
management as outlined in Section 12.5 regardless of a subject’s HLA-B*5701 status. 
 

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12.7. 
Appendix 7 – Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events 
12.7.1. 
Definition of Adverse Events 
Adverse Event Definition: 
• 
An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
• 
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 medicinal product. 
 
Events meeting AE definition include: 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., electrocardiograms, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgement of the investigator. 
• 
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 prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected 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 this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae). 
• 
The signs and symptoms and/or clinical sequelae resulting from lack of efficacy will 
be reported if they fulfill the definition of an SAE.  Also, "lack of efficacy" or 
"virological failure" also constitutes an SAE. 
 
Events NOT meeting definition of an AE include: 
• 
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 subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 
condition. 
• 
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leads to the procedure is an AE. 
• 
Situations where 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. 
12.7.2. 
Definition of Serious Adverse Events 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease, etc). 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
NOTE: 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
subject 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 hospitalization or prolongation of existing hospitalization 
NOTE: 
• 
In general, hospitalization signifies that the subject 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 out-patient setting.  Complications that occur during hospitalization are 
AEs.  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 disability/incapacity 
NOTE: 
• 
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 (e.g. sprained ankle) which may interfere or prevent everyday 
life functions but do not constitute a substantial disruption 
e. 
Is a congenital anomaly/birth defect 

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f. 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious. 
• 
Examples of such events are 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 bilirubin) 
 
12.7.3. 
Recording of SAEs and AEs leading to discontinuation of IP 
AEs and SAE Recording: 
• 
When an SAE or an AE leading to discontinuation of IP occurs, it is the 
responsibility of the investigator to review all documentation (e.g., hospital progress 
notes, laboratory, and diagnostics reports) relative to the event. 
• 
The investigator will then record all relevant information regarding an SAE or an AE 
leading to discontinuation of IP in the CRF 
• 
It is not acceptable for the investigator to send photocopies of the subject’s medical 
records to GSK in lieu of completion of the CRF pages. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records prior to 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis will be 
documented as the SAE or AE leading to discontinuation of IP, and not the 
individual signs/symptoms. 
 
12.7.4. 
Evaluating AEs and SAEs 
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 10, Section 
12.10).  
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the investigator will instead make an assessment of intensity using one of the following 
categories: 
• 
Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
and not interfering with everyday activities. 
• 
Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities 
• 
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 
the occurrence of each SAE or AE leading to discontinuation of IP. 
• 
A "reasonable possibility" is meant to convey that there are facts/evidence 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 natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated. 
• 
The investigator will also consult the most current IB and/or Product Information, for 
marketed products, in the determination of 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 when an SAE or an AE leading to discontinuation of IP has 
occurred and the investigator has minimal information to include in the initial report 
to GSK.  However, it is very important that the investigator always make an 
assessment of causality for every event prior to the initial transmission of the 
event data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information, amending the CRF accordingly. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of SAEs and AEs leading to discontinuation of IP 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 

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measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the SAE or AE leading to 
discontinuation of IP. 
• 
The investigator is obligated to assist. This may include additional laboratory tests or 
investigations, histopathological examinations or consultation with other health care 
professionals. 
• 
If a subject dies during participation in the study or during a recognized follow-up 
period, the investigator will provide 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 event data to GSK within the designated 
reporting time frames. 
 
12.7.5. 
Reporting of SAEs and AEs leading to discontinuation of IP to 
GSK/ViiV Healthcare/PPD 
Reporting to PPD via electronic data collection tool 
• 
Primary mechanism for reporting SAEs and AEs leading to discontinuation of IP to 
GSK will be the electronic data collection tool 
• 
If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE or AEs leading to discontinuation of IP CRF and fax it to the PPD 
Medical Monitor 
• 
Site will enter the event data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) 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 or AEs leading to discontinuation of IP from 
a study subject or receives updated data on such a previously reported event after the 
electronic data collection tool has been taken off-line, the site can report this 
information on a paper CRF or to the PPD Medical Monitor by telephone. 
• 
Contacts for event receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 
12.7.6. 
Reporting COVID-19 Related SAEs and AEs Leading to Treatment 
Discontinuation 
Refer to Section 12.8 (Appendix 8 COVID-19 Pandemic and Study Guidance) for 
guidance on the reporting of COVID-19 specific SAEs and AEs leading to treatment 
discontinuation. 

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12.8. 
Appendix 8 – COVID-19 Pandemic and Study Guidance 
12.8.1. 
COVID -19 Experimental Agents 
As vaccines may cause a temporary increase in the level of HIV-1 plasma RNA, it is 
highly recommended that HIV-1 RNA collection occur 2-4 weeks from COVID 
vaccination. 
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. 
12.8.2. 
COVID-19 Specific Data Capture 
12.8.2.1. 
Capturing COVID-19 Specific Protocol Deviations  
Please contact your Study CRA if protocol deviations are anticipated or occur as a result 
of COVID-19. 
12.8.2.2. 
Capturing COVID-19 Specific SAEs and AEs Leading to Treatment 
Discontinuation 
For this study, only SAEs and AEs leading to treatment discontinuation are captured in 
the eCRF. 
It is important for the study team to describe COVID-19 related Serious Adverse Events, 
or Adverse Events leading to treatment discontinuation, 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 leading to treatment discontinuation 
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 SAEs or AEs leading to treatment 
discontinuation.   
3. Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released 20 Mar 2020, represents a time point for standardized 
collection. The definitions are likely to continue to evolve. When reporting both 
serious and non- serious adverse events leading to treatment discontinuation 
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  

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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 SAE or AE leading to 
treatment discontinuation. It is important to collect the correct information from 
each participant reporting a COVID-19 SAE or AE leading to treatment 
discontinuation. Therefore, please use the CRF templates to collect this 
information.  
WHO Case Definition - March 20, 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 Covid-19 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;  

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3. Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR  
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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12.9. 
 Appendix 9 – CDC and WHO Classification Systems for HIV-
1 Infections 
CDC. Revised Surveillance Case Definition for HIV Infection – United States, 2014. 
MMWR 2014; 63 (RR-03);1-10. Available at: 
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6303a1.htm 
World Health Organization (WHO). WHO Case Definitions of HIV for Surveillance and 
Revised Clinical Staging and Immunological Classification of HIV-Related Disease in 
Adults and Children. Available at: 
https://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf  

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12.10. 
Appendix 10 – DAIDS Toxicity Scales 
U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute of Allergy and Infectious Diseases, Division of AIDS. The Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
2.1 [July 2017]. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
 
Note: 205858 Rollover Study protocol specific guidance - For the grading of creatinine 
and creatinine clearance, please refer to Section 5.4.3 and use the absolute value for 
creatinine and creatinine clearance in the DAIDS tables when determining creatinine and 
creatinine clearance DAIDS severity band. 
 

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12.11. 
Appendix 11 – Country Specific Requirements 
No country-specific requirements exist. 

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12.12. 
Appendix 12 – Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Detailed summary of changes for Protocol Amendments 1, 2, and 3 are contained within 
Section 12.11 (Appendix 11) of Protocol Amendment 3.  
ViiV Healthcare/ 
GlaxoSmithKline 
Document Number 
Date 
Version 
2016N282439_00 
23-AUG-2016 
Original 
2016N282439_01 
26-SEP-2016 
Amendment No. 1 
Patients enrolling at sites in some countries without approval for pediatric dosing of 
dolutegravir need to be enrolled in a Phase IIIB study. Therefore, the development stage 
of the protocol has been changed from a Phase IV to a Phase IIIB study in order to 
account for these global regulatory requirements. In addition, we have made minor 
changes to the exclusion criteria in response to feedback from the FDA. 
2016N282439_02 
29-JUN-2018 
Amendment No. 2 
The potential risk for neural tube defects has been added to the risk:benefit section. 
Dosing tables were updated to align to the parent study (P1093).  Background 
information on the parent study (P1093) was updated, including sample size.  Reference 
to collection of PK samples, which were included in error, have been removed.  Other 
clarifying text and correction of typographical errors have been addressed. 
2016N282439_03 
27-JUN-2019 
Amendment No. 3 
Amendment 03 incorporates the transition of subjects from a second parent study, P2019, 
into this open label rollover study.   
The study will provide access to age appropriate formulations of dolutegravir (DTG), 
either as Tivicay or as fixed dose combination (FDC) abacavir/dolutegravir/lamivudine 
(ABC/DTG/3TC), to eligible subjects who have completed the P1093 Study or P2019 
parent studies. 
Both parent studies P1093 and P2019 are sponsored by the Division of Acquired 
Immunodeficiency Syndrome (DAIDS) the National Institute of Allergy and Infectious 
Disease (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD) and implemented by the International Maternal 
Paediatric Adolescent AIDS Clinical Trial Network (IMPAACT). P2019 is a Phase I/II 
study which examines the pharmacokinetics, safety, and tolerability of 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) dispersible and immediate release 
tablets in HIV-1-infected children less than 12 years of age.  
ViiV Healthcare plans to seek licensure of ABC/DTG/3TC for pediatric use in countries 

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where parent study P2019 is conducted. In countries where ABC/DTG/3TC is not locally 
available in the age appropriate formulation at the time of subject completion of the 
P2019 study, and where the subject is deriving benefit from ABC/DTG/3TC, ViiV 
Healthcare will provide ABC/DTG/3TC to subjects within this ViiV sponsored study. 
Criteria for inclusion and management of subjects from P2019 were embedded 
throughout the protocol. 
Liver chemistry stopping criteria, required use of contraception, and criteria for IP restart 
were updated to reflect ViiV Healthcare guidance for DTG and DTG containing products 
in ViiV sponsored studies. 
2016N282439_04 
10-DEC-2020 
Amendment No. 4 
To more closely align with subject management in the IMPAACT P1093 and P2019 
parent protocols, eligibility criteria were clarified.  
Virologic failure due to non-adherence, intercurrent illness or other factors not associated 
with the study drug, did not automatically lead to permanent discontinuation of study 
drug and participant withdrawal from the DAIDS sponsored parent studies (IMPAACT 
P1093 and P2019).  Therefore, subjects may have experienced confirmed virologic 
failure with subsequent virologic control and evidence of ongoing clinical benefit from 
the study drug while in the parent studies.   
Eligibility for participation in the 205858 study was clarified throughout the protocol 
with the removal of references to ‘no evidence of virologic failure in the parent studies’ 
and the addition of inclusion criterion #3, which requires confirmation of supporting 
evidence of the subject’s continued benefit from use of the Investigational Product during 
participation in the parent study. Evidence of virologic control at the time of completion 
of the parent study (inclusion criterion #2, confirmed by viral load) is also required. In 
addition, exclusion criterion #1 was added to exclude participants who have had 
confirmed virologic failure with evidence of resistance to either a) DTG in the P1093 
parent study or b) ABC, DTG or 3TC (with the exception of M184V) in the P2019 parent 
study. 

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Section #  
and Name 
Description of Change 
Brief Rationale 
Title Page 
Modified title page formatting. (No 
change to study specific information).  
Formatting was updated to align with current 
revised ViiV Healthcare Clinical Protocol Master 
Template title page 
Protocol Amendment 
Summary of 
Changes 
The protocol amendment revision 
chronology section was updated to 
provide rationale and changes for 
Protocol Amendment 04.  Rationale for 
prior Protocol Amendments 01, 02 and 
03 were moved to Section 12.13 
(Appendix 13) 
The Protocol Amendment Summary of Changes 
section was modified to align with the current ViiV 
Healthcare Clinical Protocol Master Template and 
process for documentation of protocol amendment 
changes. 
Revised text from Protocol Amendments 01, 02 
and 03 can be found in Section 12.11 (Appendix 
11, Protocol Changes) of prior Protocol 
Amendment 03.   
Throughout 
Added the marketed name the for 
dolutegravir (DTG) dispersible tablet in 
the United States - ‘Tivicay PD’. 
In the United States, the DTG dispersible tablet 
was approved and is marketed as Tivicay PD™.  
Reference to the approval and marketed name 
(Tivicay PD™) was incorporated. 
Throughout 
Where DTG was referenced as ‘Tivicay’, 
‘Tivicay’ was replaced with ‘single entity 
DTG’ or ‘DTG’.  
‘Single entity DTG’ or ‘DTG’ was used to more 
inclusively references both Tivicay and Tivicay PD 
marketed names. 
4.6.1 Risk 
Assessment for DTG 
Incorporated updated neural tube defect 
data from the birth outcomes surveillance 
study conducted in Botswana. 
Aligned with current DTG Investigator’s Brochure. 
4.6.1 Risk 
Assessment for DTG 
4.6.2 Risk 
Assessment for 
ABC/DTG/3TC 
Theoretical risk of serious drug 
interaction with fampridine was 
incorporated. 
Aligned with current DTG Investigator’s Brochure. 
4.6.2 Risk 
Assessment for 
ABC/DTG/3TC 
Updated to note ABC/DTG/3TC FDC 
should not be used in participants with 
creatinine clearance of less than 30 
mL/min because, whilst no dosage 
adjustment of DTG or ABC is necessary 
in patients with renal impairment, dose 
reduction is required for the 3TC 
component. 
Aligned with current DTG Investigator’s Brochure. 
4.6.3 Benefit 
Assessment 
Updated safety and efficacy information 
for DTG pediatric P1093 and Odyssey 
studies.  
Updated to align with current available data. 
5.1 Inclusion Criteria 
(Inclusion Criterion 1, 
Duration in parent 
Removed sub bullet which notes that 
subjects with evidence of virologic failure 
in either parent study must have eligibility 
For clarity, a third separate inclusion criterion was 
added requiring evidence of continued benefit from 
IP during the subject’s participation in the parent 

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studies) 
for this rollover study discussed and 
agreed with the ViiV Healthcare Medical 
Monitor.  
study (P1093 or P2019). Investigators will submit a 
clinical summary, verifying continued benefit, to the 
Study Medical Monitor for confirmation of criterion 
eligibility. 
5.1 Inclusion Criteria 
(Inclusion Criterion 2, 
Virologic control at 
Screening) 
Clarification added to note that a single 
HIV-1 RNA retest may be completed prior 
to the Day 1 visit to confirm virologic 
control criterion has been met. 
A single HIV-1 RNA retest may be completed prior 
to Day 1 if needed. Virologic control must be 
confirmed prior to enrolment (Day 1 visit).  
5.1 Inclusion Criteria 
(Inclusion Criterion 3, 
Evidence of clinical 
benefit in parent 
studies) 
A third separate inclusion criterion was 
added requiring evidence of continued 
benefit from IP during the subject’s 
participation in the parent study (P1093 
or P2019). Investigators will submit a 
clinical summary, verifying continued 
benefit, to the Study Medical Monitor for 
confirmation of criterion eligibility. 
Added to confirm evidence of clinical benefit from 
IP during participation in the parent studies.  
5.2 Exclusion Criteria 
(Exclusion Criterion 
1) 
Exclusion criterion 1 was incorporated to 
exclude subjects who have had 
confirmed virologic failure with evidence 
of resistance to a) either DTG in the 
P1093 parent study or b) ABC, DTG or 
3TC (with the exception of M184V) in the 
P2019 parent study. 
Added to mitigate risk related to inclusion of 
subjects with prior resistance to DTG, ABC or 3TC 
and potential interference with continued benefit 
from IP.  
5.2 Exclusion Criteria 
(Exclusion Criterion 
3)  
A timeframe of ‘30 days prior to study 
entry’ was added to exclusion criterion 3: 
‘Known ≥Grade 3 laboratory toxicities 
within 30 days prior to study entry…’ 
Added for clarity. 
5.4.3 Management of 
Renal Toxicity 
 
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 was also provided.  
Modifications were made to clarify and simplify 
participant management. Stepwise instructions 
were incorporated, 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 were incorporated. 
6.1.1 Medical 
Devices 
7.6.1.5  Medical 
Device Deficiencies 
7.6.1.6 Time Period 
for Detecting Medical 
Device Deficiencies 
 7.6.1.7 Prompt 
Added description of equivalent locally 
sourced medical devices for this study 
(dosing cup/syringe). 
Added the definition of a Device 
Deficiency and requirements for 
reporting. 
Device Deficiency safety reporting requirements 
were incorporated into the protocol for alignment 
with the United States Food and Drug 
Administration (US FDA) 21 CFR 4 Subpart B 
(Regulation of Combination Products). 

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reporting of Medical 
Device Deficiencies 
to the Sponsor    
12.8 Appendix 8 
Reporting a Medical 
Device Deficiency 
6.5.2 DTG 
Dispersible Tablets 
Updated to include current dispersion 
volumes for administration of the 
dispersible tablets, and instruction for a 5 
mL water rinse following consumption of 
medication dose.  
Updated to align with changes applied to parent 
protocol and Instructions for Use. 
6.5.3 ABC/DTG/3TC 
Dispersible Tablets 
Updated to include most current 
dispersion volumes for administration of 
the dispersible tablets, and instruction for 
a 15 mL water rinse following 
consumption of medication dose. 
Updated to align with changes applied to parent 
protocol and Instructions for Use. 
6.5.4 ABC/DTG/3TC 
Immediate Release 
(Triumeq™) Tablets 
Updated to align with most current 
description of the product and storage 
conditions. 
Updated to align with changes applied to parent 
protocol and Instructions for Use. 
6.11.1 Permitted 
Medications 
Instruction added for Investigators to 
consult with the Study Medical Monitor if 
any treatments for COVID-19 are 
planned for a study subject.  
To ensure relevant drug interactions are 
considered and continuation of the subject in the 
study remains appropriate.   
6.11.4 Additional 
considerations for 
ABC/DTG/3TC 
Guidance pertaining to the use of 
riociguat was incorporated. 
Guidance added to note that the pediatric 
weight based once daily dose of the 
single entity DTG should be administered 
twice daily when ABC/DTG/3TC is co-
administered with certain enzyme 
inducing drugs. 
-Concomitant administration of a single dose of 
riociguat (0.5 mg) to HIV patients receiving 
DTG/ABC/3TC FDC led to an approximately three-
fold higher riociguat AUC(0-∞) when compared to 
historical riociguat AUC(0-∞) reported in healthy 
participants. Riociguat dose may need to be 
reduced, consult the riociguat product labelling for 
dosing recommendations 
Aligned with current DTG Investigator’s Brochure 
7.6.2.2 Pregnancy 
Reporting  
12.3.2 
Collection of 
Pregnancy 
Information 
Required timeframe for reporting subject 
pregnancy to the sponsor was changed 
from ‘within 2 weeks’ to ‘within 24 hours’. 
Alignment with updated ViiV Healthcare SOP and 
current ViiV Healthcare Clinical Protocol Master 
Template. 
10.2.1 Children in 
care 
Additional guidance for management and 
tracking of children in care (children who 
are wards of state or any other agency, 
institution or entity) has been added to 
Section 10.2.1 (Children in care). 
Children in care are a vulnerable population. Close 
monitoring is required to confirm evidence of 
appropriate guardianship within the context of 
available IRB/IEC guidance, local law, regulation 
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the study will be monitored for child in care status 
at screening and for any changes in status 
throughout study conduct.  
12.2.2 (Appendix 2) 
Dosing Tables - DTG 
Dispersible Tablets  
Dosing table section was simplified. 
Table ‘R’ was added. 
Updated to align with current dosing instruction 
provided in the P1093 parent protocol. 
12.6 (Appendix 6) 
Toxicity 
Management 
Cross reference to Section 12.6.1  
(Specific Toxicities/Adverse Event 
Management) was inserted.  
Guidance for the management of specific toxicities 
(such as allergic reaction, rash, liver chemistry and 
others) are found in Section 12.6.1 of the protocol. 
Section 12.6.1 (Specific Toxicities/Adverse Event 
Management) should be used as the primary 
reference for management of specific conditions 
noted.  
12.9 (Appendix 9) 
COVID-19 Pandemic 
and Study Guidance 
Instructions for safety reporting and data 
capture of COVID-19 related SAEs or 
AEs leading to treatment discontinuation 
were incorporated. 
It is important to describe COVID 19 related 
SAEs/AEs leading to treatment discontinuation and 
impact on study data and outcomes. 
Standardization of case definitions will facilitate 
future data analysis. 
 

Signature Page for  205858 TMF-14008177 v2.0
Signature Page for TMF-14008177 v2.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 21-Jun-2022 19:24:44 GMT+0000
PPD