Conditions: Infection, Human Immunodeficiency Virus HIV Infections
Keywords: antiretroviral therapy naïve women once daily HIV infection atazanavir tenofovir/emtricitabine dolutegravir/abacavir/lamivudine fixed dose combination integrase inhibitor ritonavir
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 499
Healthy volunteers: no

Brief summary:
This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)

Detailed description:

Arms:
arm 1: As per the randomization schedule subjects will be administered with DTG/ABC/3TC (50mg/600mg/300mg) FDC tablet OD up to Week 48 and if continued if applicable in the Continuation Phase. DTG/ABC/3TC FDC may be administered with or without food arm 2: As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food

Interventions: intervention 1: Dolutegravir/abacavir/lamivudine FDC intervention 2: Atazanavir intervention 3: Ritonavir intervention 4: Tenofovir/emtricitabine FDC
Intervention descriptions: intervention 1: Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg intervention 2: Atazanavir capsule 300 mg intervention 3: Ritonavir tablet 100 mg intervention 4: Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC

Protocol document:
Prot_000.pdf: 
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Vii V H e alt h c ar e a n d T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s
I N G 1 1 7 1 7 2
1
TI T L E P A G E
Di visi o n: W orl d w i de De vel o p me nt
I nf or m ati o n T y pe: Pr ot oc ol A me n d me nt
Title:
A P hase III b, ra n d o mize d, o pe n-la bel st u d y of t he safet y a n d 
efficac y of d ol ute gra vir/a baca vir/la mi v u di ne o nce dail y 
c o m pare d t o ataza na vir a n d rit o na vir pl us te n of o vir /e mtricita bi ne 
o nce dail y i n HI V -1 i nfecte d a ntiretr o viral t hera p y naï ve w o me n
C o m p o u n d N u m ber:
G S K 1 3 4 9 5 7 2 + G R 1 0 9 7 1 4 + GI 2 6 5 2 3 5
( G S K 2 6 1 9 6 1 9)
Effecti ve D ate:
1 9- J U N-2 0 1 8
Pr ot oc ol A me n d me nt N u m ber:  0 3
S u bject: HI V i nfecti o n, i nte grase i n hi bit or, d ol ute gra v ir/a baca vir/la mi v u di ne fi xe d d ose 
c o m bi nati o n, o nce dail y, ataza na vir, rit o na vir, te n of o vir/e mtricita bi ne, a ntiretr o viral 
t hera py naï ve, w o me n
A ut h or s:
 
C o p y ri g ht 2 0 1 8 t he Vii V Healt hcare a n d Gla x o S mit h Kli ne gr o u p of c o m pa nies.  All 
ri g hts reser ve d.  U na ut h orise d c o p yi n g or use of t his i nf or mati o n is pr o hi bite d.
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2013N161649_03
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ViiV Healthcare and The GlaxoSmithKline group of companies
ING117172
2
Revision Chronology:
2013N161649_00
2013-MAY-31
Original
2013N161649_01
2013-AUG-12
Amendment No. 01 
This amendment includes the removal of the Child-Pugh Classification due to its 
unsuitability for use in subjects with no known hepatic impairment.  Other minor 
clarifications and corrections have been incorporated, including an update to Figure 2, 
Virologic Criteria for Subject Management at Week 24, to differentiate between the two 
scenarios for re-testing HIV-1 RNA levels.
2013N161649_02
2014-AUG-11
Amendment No. 2
Changes made to the UK country specific information on study duration (Appendix 5) to 
comply with requests from the UK MHRA. The medical monitor contact information has 
also been updated
2013N161649_03
2018-JUN-19
Amendment No. 3
Changes were made to the protocol to manage and mitigate risks following identification 
of a potential safety issue related to neural tube defect in infants born to women with 
exposure to dolutegravir at the time of conception.

The Risk Assessment table (Section 1.3.1.) was updated to include language 
regarding risk and mitigation of neural tube defects.

Inclusion criterion #2 (Section 4.2.) was updated to exclude the double barrier method 
of contraception, and refer to the Modified List of Highly Effective Methods for 
Avoiding Pregnancy in Females of Reproductive Potential.

The withdrawal criteria (Section 4.5.) were updated to include a reminder that 
females of reproductive potential who change their minds and desire to be pregnant, 
or who state they no longer are willing to comply with the approved pregnancy 
avoidance methods, should also be withdrawn from the study.

The Time and Events table (Section 6.1.) was updated to include a reminder for 
investigators to check at every visit that females of reproductive potential are 
avoiding pregnancy.

Appendix 6 was added: Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential
Administrative updates were made.


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S P O N S O R I N F O R M A TI O N P A G E
Cli nic al St u d y I de ntifier: I N G 1 1 7 1 7 2
T his st u d y  is s p o ns ore d b y Vii V Healt hcare.  Gla x o S mit h Kli ne is res p o nsi ble f or 
i m ple me nti n g a n d ma na gi n g all as pects of t his st u d y.
S p o ns or Le g al Re gistere d A d dress:
Vii V Healt hcare
9 8 0 Great West R oa d
Bre ntf or d
Mi d dlese x
T W 8 9 G S
U K
Tele p h o ne:  + 4 4 ( 0) 2 0 8 3 8 0 6 2 0 0
S p o ns or C o nt act A d dress:
Vii V Healt hcare
Fi ve M o ore Dri ve
Researc h Tria n gle Par k, N ort h Car oli na U S A 
2 7 7 0 9 - 3 3 9 8
Tele p h o ne:  + 1 8 7 7 8 4 4 8 8 7 2
I n s o me c o u ntries, the cli nical trial s p o ns or ma y  be t he l ocal Vii V Healt hcare affiliate 
c o m pa n y ( or desi g nee). W here a p plica ble, t he details of t he S p o ns or a n d c o ntact pers o n 
will be pr o vi de d t o t he rele va nt re g ulat or y  a ut h orit y as part of t he cli nical trial 
s u b missi o n.
Me di c al M o nit or C o nt act I nf or m ati o n a n d Seri o us A d verse E ve nts ( S A E) C o nt act 
I nf or m ati o n: 
 M D
Vii V Healt hcare,
5 M o ore Dri ve, 
Researc h Tria n gle Par k, N C 2 7 7 0 9, U S A
M o bile: 
Facsi mile: 
e-mail: 
Re g ul at or y A ge nc y I de ntif yi n g N u m bers:
U S I N D: 1 1 4, 8 2 0
E u dra C T: 2 0 1 2 - 0 0 5 8 2 3- 3 4
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INVESTIGATOR AGREEMENT PAGE
For protocol number ING117172
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 clinical 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 Signature
Date


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6
TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS...........................................................................................10
PROTOCOL SUMMARY...............................................................................................13
1.
INTRODUCTION....................................................................................................16
1.1.
Background ................................................................................................16
1.2.
Rationale ....................................................................................................18
1.2.1.
Principle of Dose Selection ..........................................................18
1.2.2.
Impact of Potential Drug-Drug Interaction ....................................19
1.2.2.1.
Use of calcium and iron supplements with 
dolutegravir ................................................................19
1.3.
Benefit:Risk Assessment ............................................................................20
1.3.1.
Risk Assessment .........................................................................21
1.3.2.
Benefit Assessment.....................................................................26
1.3.3.
Overall Benefit:Risk Conclusion...................................................26
2.
OBJECTIVES.........................................................................................................26
3.
INVESTIGATIONAL PLAN.....................................................................................27
3.1.
Study Design ..............................................................................................27
3.2.
Discussion of Design ..................................................................................29
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA.......................................30
4.1.
Number of Subjects ....................................................................................30
4.2.
Inclusion Criteria.........................................................................................30
4.3.
Exclusion Criteria........................................................................................32
4.4.
Other Eligibility Criteria Considerations.......................................................34
4.5.
Withdrawal Criteria .....................................................................................34
4.5.1.
Virologic Criteria for Subject Management and Viral 
Resistance Testing ......................................................................36
4.6.
Screening Failures......................................................................................38
5.
STUDY TREATMENTS..........................................................................................38
5.1.
Investigational Product and Other Study Treatment....................................38
5.1.1.
Tablet Formulation of DTG/ABC/3TC FDC ..................................39
5.1.2.
Tablet Formulations of ATV, RTV, TDF/FTC FDC .......................39
5.1.3.
Dosage and Administration..........................................................39
5.2.
Treatment Assignment................................................................................40
5.3.
Blinding.......................................................................................................40
5.4.
Product Accountability ................................................................................40
5.5.
Treatment Compliance................................................................................40
5.6.
Concomitant Medications and Non-Drug Therapies....................................40
5.6.1.
Permitted Medications and Non-Drug Therapies..........................41
5.6.2.
Prohibited Medications and Non-Drug Therapies.........................41
5.6.2.1.
Prohibited medications for subjects 
randomized to DTG/ABC/3TC FDC............................42
5.6.2.2.
Prohibited medications for subjects 
randomized to ATV+RTV + TDF/FTC FDC.................42
5.7.
Treatment after the End of the Study ..........................................................43
5.8.
Treatment of Study Treatment Overdose....................................................43


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6.
STUDY ASSESSMENTS AND PROCEDURES .....................................................44
6.1.
Time and Events Schedule .........................................................................44
6.2.
Critical Baseline Assessments....................................................................47
6.2.1.
Screening Assessments ..............................................................47
6.2.2.
Baseline (Day 1) Assessments ....................................................47
6.2.3.
Subjects infected with Hepatitis B (HBV) and/or 
Hepatitis C (HCV) ........................................................................48
6.3.
Efficacy.......................................................................................................48
6.3.1.
Efficacy Evaluations.....................................................................48
6.3.2.
Primary Endpoint .........................................................................48
6.3.3.
Secondary Efficacy Endpoints .....................................................49
6.4.
Safety .........................................................................................................49
6.4.1.
Safety Evaluations.......................................................................49
6.4.2.
Safety Endpoints..........................................................................51
6.4.3.
Toxicity Management...................................................................51
6.4.4.
Specific Toxicities/Adverse Event Management...........................52
6.4.4.1.
Liver Chemistry Stopping and Follow up 
Criteria........................................................................53
6.4.4.2.
Restarting Investigational Product ..............................55
6.4.4.3.
ATV related hyperbilirubinemia...................................56
6.4.4.4.
Hypertriglyceridemia/Hypercholesterolemia................56
6.4.4.5.
CPK Elevation ............................................................56
6.4.4.6.
Decline in Renal Function...........................................56
6.4.4.7.
Proteinuria..................................................................57
6.4.4.8.
Allergic Reaction ........................................................57
6.4.4.9.
Abacavir Hypersensitivity Reaction (ABC HSR)..........58
6.4.4.10.
Skin reactions without other symptoms that are 
typical of ABC HSR ....................................................59
6.4.5.
Adverse Events............................................................................60
6.4.5.1.
Definition of an AE......................................................60
6.4.5.2.
Definition of an SAE ...................................................61
6.4.6.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs.........................................................62
6.4.7.
Cardiovascular Events.................................................................63
6.4.8.
Death Events...............................................................................63
6.4.9.
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs...............................................63
6.4.10.
Suicidality Monitoring...................................................................64
6.4.11.
Pregnancy ...................................................................................64
6.4.11.1.
Pregnancy Testing......................................................64
6.4.11.2.
Action to be Taken if Pregnancy Occurs.....................65
6.4.11.3.
Time Period for Collecting Pregnancy 
Information .................................................................65
6.4.12.
Time Period and Frequency of Detecting AEs and SAEs.............65
6.4.13.
Method of Detecting AEs and SAEs.............................................65
6.4.14.
Prompt Reporting of Serious Adverse Events and Other 
Events to GSK.............................................................................66
6.4.14.1.
Regulatory Reporting Requirements for SAEs............67
6.4.15.
Other Safety Outcomes ...............................................................68
6.5.
Health Outcomes........................................................................................68
6.5.1.
Health Outcomes Endpoints ........................................................68
6.6.
Viral Genotyping and Phenotyping..............................................................69


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6. 6. 1. 
Vir ol o g y E n d p oi nt s .......................................................................6 9
6. 6. 2.
HI V- 1 P ol y m er a s e Vir al G e n ot y pi n g a n d P h e n ot y pi n g .................6 9
6. 7.
P h ar m a c o g e n eti c R e s e ar c h ........................................................................7 0
7.
D A T A M A N A G E M E N T ...........................................................................................7 0
8.
D A T A A N A L Y SI S A N D S T A TI S TI C A L C O N SI D E R A TI O N S ...................................7 0
8. 1.
H y p ot h e s e s .................................................................................................7 0
8. 2.
St u d y D e si g n C o n si d er ati o n s ......................................................................7 1
8. 2. 1.
S a m pl e Si z e A s s u m pti o n s ...........................................................7 1
8. 2. 2.
S a m pl e Si z e S e n siti vit y ................................................................7 3
8. 2. 3.
S a m pl e Si z e R e -e sti m ati o n ..........................................................7 4
8. 3.
D at a A n al y si s C o n si d er ati o n s .....................................................................7 4
8. 3. 1.
A n al y si s P o p ul ati o n s ....................................................................7 4
8. 3. 2.
A n al y si s D a t a S et s.......................................................................7 5
8. 3. 3.
Tr e at m e nt C o m p ari s o n s ..............................................................7 5
8. 3. 3. 1.
Pri m ar y C o m p ari s o n s of I nt er e st ................................7 5
8. 3. 3. 2.
Ot h er C o m p ari s o n s of I nt er e st ....................................7 5
8. 3. 4.
I nt eri m A n al y si s ...........................................................................7 6
8. 3. 5.
K e y El e m e nt s of A n al y si s Pl a n ....................................................7 6
8. 3. 5. 1.
Effi c a c y A n al y s e s .......................................................7 6
8. 3. 5. 2.
S af et y A n al y s e s ..........................................................7 7
8. 3. 5. 3.
H e alt h O u t c o m e s A n al y s e s ........................................7 8
8. 3. 5. 4.
Vir al G e n ot y pi n g/ P h e n ot y pi n g A n al y s e s .....................7 8
8. 3. 5. 5.
P h ar m a c o g e n eti c A n al y s e s ........................................7 8
9.
S T U D Y C O N D U C T C O N SI D E R A TI O N S ...............................................................7 8
9. 1.
P o sti n g of I nf or m ati o n o n P u bli cl y A v ail a bl e Cli ni c al Tri al R e gi st er s ............7 8
9. 2.
R e g ul at or y a n d Et hi c al C o n si d er ati o n s, I n cl u di n g t h e I nf or m e d 
C o n s e nt Pr o c e s s ........................................................................................7 9
9. 3.
Q u alit y C o ntr ol ( St u d y M o nit ori n g) ..............................................................7 9
9. 4.
Q u alit y A s s ur a n c e .......................................................................................8 0
9. 5.
St u d y a n d Sit e Cl o s ur e ...............................................................................8 0
9. 6.
R e c or d s R et e nti o n ......................................................................................8 0
9. 7.
Pr o vi si o n of St u d y R e s ult s t o I n v e sti g at or s, P o sti n g of I nf or m ati o n 
o n P u bli cl y A v ail a bl e Cli ni c al Tri al s R e gi st er s a n d P u bli c ati o n ....................8 1
1 0.
R E F E R E N C E S .......................................................................................................8 2
1 1.
A P P E N DI C E S ........................................................................................................8 5
1 1. 1.
A p p e n di x 1: C D C Cl a s s ifi c ati o n S y st e m f or HI V-1 I nf e cti o n s ( 1 9 9 3) ...........8 5
1 1. 2.
A p p e n di x 2 : Di vi si o n of AI D S T a bl e f or Gr a di n g t h e S e v erit y of A d ult 
a n d P e di atri c A d v er s e E v e nt s .....................................................................8 8
1 1. 3.
A p p e n di x 3: P h ar m a c o g e n eti c R e s e ar c h ..................................................1 0 7
1 1. 4.
A p p e n di x 4: Li v er S af et y Dr u g R e st art or R e c h all e n g e G ui d eli n e s ............1 1 3
1 1. 5.
A p p e n di x 5: C o u ntr y S p e cifi c R e q uir e m e nt s .............................................1 1 9
1 1. 6.
A p p e n di x 6: M o difi e d Li st of Hi g hl y Eff e cti v e M et h o d s f or A v oi di n g 
Pr e g n a n c y i n F e m al e s of R e pr o d u cti v e P ot e nti al ( F R P) ...........................1 2 0
1 1. 7.
A p p e n di x 7: Pr ot o c ol C h a n g e s ..................................................................1 2 1
1 1. 7. 1.
Pr ot o c ol A m e n d m e nt 0 1 ( 1 2 -A U G -2 0 1 3) ...................................1 2 1
C CI


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11.7.2.
Protocol changes for Amendment 02 (11-AUG-2014) from 
Amendment 01 (12-AUG-2013) .................................................125
11.7.3.
Protocol changes for Amendment 03 (19-JUN-2018) from 
Amendment 02 (11-AUG-2014) .................................................127


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LIST OF ABBREVIATIONS
3TC
Lamivudine, EPIVIR
AE
Adverse Event
ABC
Abacavir, ZIAGEN
ABC/3TC 
Abacavir/Lamivudine, EPZICOM, KIVEXA
AIDS
Acquired immunodeficiency syndrome
ALT
Alanine Aminotransferase
ART
Antiretroviral Therapy
AST
Aspartate Aminotransferase
ATV
Atazanavir, Reyataz
BID
Twice Daily
BUN
Blood urea nitrogen
c/mL
Copies/milliliter
CC
Calcium carbonate
CD4+
Helper-inducer T-lymphocyte having surface antigen CD4 (cluster of 
differentiation 4)
CDC
Centers for Disease Control and Prevention
CI
Confidence Interval
CMH
Cochran-Mantel-Haenszel
COBI
Cobisistat
CPK
Creatine Phosphokinase
CrCL
Creatinine clearance
CRF
Case Report Form
CSR
Clinical Study Report
C-SSRS
Columbia Suicidality Severity Rating Scale
DAIDS
Division of Acquired Immunodeficiency Syndrome
DILI
Drug Induced Liver Injury
DNA
Deoxyribonucleic Acid
DTG
Dolutegravir
ECG
Electrocardiograph
EFV
Efavirenz
ELV
Elvitegravir
EMA
European Medicines Agency
FDA
Food and Drug Administration
FDC
Fixed dose combination
FF
Ferrous Fumerate
FRP
Females of Reproductive Potential
FTC
Emtricitabine
GCP
Good Clinical Practices
GCSP
Global Clinical Safety and Pharmacovigilance  
GFR
Glomerular filtration rate
GI
Gastrointestinal
GSK
GlaxoSmithKline
HBsAg
Hepatitis B Virus surface Antigen
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HDL
High Density Lipoprotein


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HIV-1
Human Immunodeficiency Virus Type 1
HIVTSQ
HIV Treatment Satisfaction Questionnaire
HLA
Human Leukocyte Antigen
HRQoL
Health Related Quality of Life
HSR
Hypersensitivity Reaction
IB
Investigator’s Brochure
ICH
International Conference on Harmonization 
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
INI
Integrase inhibitor
IP
Investigational Product
IRB
Institutional Review Board
IRIS
Immune Reconstitution Inflammatory Syndrome
ITT
Intent to Treat
IUD
Intrauterine Device
LDH
Lactic Dehydrogenase
LDL
Low Density Lipoprotein
LLOD
Lower Limit of Detection
LSLV
Last subject’s last visit
MAA
Marketing Application Authorisation
MCS
Mental Component Summary
MCV
Mean Corpuscular Volume
MSDS
Material Safety Data Sheet 
mg
Milligram
mL
Milliliter
NCEP
National Cholesterol Education Program
NRTI
Nucleoside Reverse Transcriptase Inhibitor
PCS
Physical Component Summary
PGx
Pharmacogenetic
PK
Pharmacokinetic
Pol
Polymerase
PP
Per Protocol
PRO
Protease
PRTD
Proximal Renal Tubule Dysfunction
PSRAE
Possible Suicidality Related Adverse Event
QTC
Corrected QT interval
RAL
Raltegravir, Isentress
RAP
Reporting and Analysis Plan
RBC
Red Blood Cells
RNA
Ribonucleic acid
RT
Reverse Transcriptase
RTV
Ritonavir, Norvir
SAE
Serious Adverse Event
SF-12
12-Item Short Form Health Survey
SJS
Stevens Johnson Syndrome
SPM
Study Procedure Manual
STR
Single Tablet Regimen
TEN
Toxic Epidermal Necrolysis


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TDF
Tenofovir disoproxil fumarate, Viread
TLOVR
Time to Loss of Virologic Response
ULN
Upper limit of normal
VSLC
ViiV Safety and Labeling Committee
WBC
White blood cells
Trademark Information
Trademarks of ViiV Healthcare
Trademarks not owned by ViiV 
Healthcare
EPIVIR
Atripla 
(efavirenz/tenofovir/emtricitabine)
EPZICOM
Complera (rilpivirine/tenofovir/ 
emtricitabine)
KIVEXA
GenoSure
TRIZIVIR
Isentress (raltegravir)
ZIAGEN
Monogram Biosciences
Norvir (ritonavir)
Phenosense
Quest Diagnostics
Reyataz (atazanavir)
Stribild (elvitegravir/cobicistat/ 
tenofovir/emtricitabine)
Truvada (tenofovir/emtricitabine)


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PROTOCOL SUMMARY
Rationale
The dolutegravir, abacavir and lamivudine fixed dose combination (DTG/ABC/3TC 
FDC) may provide a better treatment option for women infected with Human 
Immunodeficiency Virus Type 1 (HIV-1) due to its robust antiviral activity, safety 
profile, high barrier to resistance, low potential for drug-drug interactions, and 
administration as a once-daily single tablet regimen (STR). Currently available integrase 
inhibitors (INIs), elvitegravir (ELV) and raltegravir (RAL), have limitations including the 
development of clinical resistance, the need for a twice daily (BID) regimen for RAL 
administration, and a pharmacokinetic (PK) booster for ELV administration, which leads 
to an increased potential for drug-drug interactions including with oral contraceptives.  
Only limited data on DTG in women are available in Phase III studies due to lower 
enrollment of women compared with men. Therefore, a powered study of DTG in a 
single tablet regimen with ABC and 3TC will be conducted in women to provide robust 
data on safety and efficacy in this population.  
Study ING117172 is a Phase IIIb trial designed to demonstrate the non-inferior antiviral 
activity of DTG/ABC/3TC FDC once daily compared to atazanavir plus ritonavir 
(ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination 
(TDF/FTC FDC) all administered once daily in HIV-1 infected, antiretroviral therapy 
(ART)-naïve women over 48 weeks.  This study will also characterize the safety and 
tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC.  
Objectives
Primary Objective

To demonstrate the non-inferior antiviral activity of DTG/ABC/3TC FDC once daily 
compared to ATV+RTV+TDF/FTC FDC each administered once daily over 48 
weeks in HIV-1 infected ART-naïve women.
Secondary Objectives

To evaluate the antiviral and immunological activity and incidence of disease 
progression (HIV-associated conditions, acquired immunodeficiency syndrome 
[AIDS] and death) of DTG/ABC/3TC FDC once daily compared to 
ATV+RTV+TDF/FTC FDC once daily over time;

To compare the safety, tolerability, and laboratory parameters of DTG/ABC/3TC
FDC once daily to ATV+RTV+TDF/FTC FDC once daily over time;

To assess the development of viral resistance in subjects who meet confirmed 
virologic withdrawal criteria;

To evaluate renal markers (in urine and blood), and bone markers (in blood) in 
subjects treated with DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC;


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
To assess treatment satisfaction, and change in health-related quality-of-life for 
subjects treated with DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC;

To evaluate the effect of patient characteristics (i.e., demographic factors, HIV-1 
subtype, Baseline CD4) on response to DTG/ABC/3TC FDC compared to 
ATV+RTV+TDF/FTC FDC over time.
Study Design
This study is a Phase IIIb randomized, open-label, active-controlled, multicenter, parallel 
group, non-inferiority study.  The study will be conducted in approximately 474 HIV-1 
infected ART-naïve women. Subjects will be randomized 1:1 to receive a FDC of DTG 
50mg/ ABC 600mg/ 3TC 300mg once daily or ATV 300mg plus RTV 100mg and TDF 
300mg/ FTC 200mg FDC each administered once daily. Randomization will be stratified 
by Screening plasma HIV-1 RNA (100,000 copies/mL [c/mL] or >100,000 c/mL) and 
CD4+ cell count (350 cells/mm3 or >350 cells/mm3).  The study will comprise a 
Screening Phase (approximately 14-28 days), a Randomized Phase (48 weeks), and a 
Continuation Phase. The primary analysis will take place after the last subject completes 
48 weeks of therapy. No dose reductions, modifications in dosage, or changes in the 
frequency of dosing of any components of each regimen will be allowed in this study.  
Subjects randomized to receive DTG/ABC/3TC FDC who successfully complete 
48 weeks of treatment will continue to have access to DTG/ABC/3TC FDC 
(Continuation Phase) until it is either locally approved and commercially available, the 
patient no longer derives clinical benefit, the patient meets a protocol-defined reason for 
discontinuation, or development of DTG/ABC/3TC FDC is terminated.  Subjects 
randomized to the ATV+RTV+TDF/FTC arm will receive ATV+RTV+TDF/FTC FDC 
through their Week 48 visit only, after which they will complete the study and will need 
to have alternate arrangements in place to access antiretroviral medication. 
Study Endpoints/Assessments
The primary endpoint for this study will be the proportion of subjects with plasma HIV-1 
RNA <50 c/mL at Week 48 using the Snapshot algorithm (Missing, Switch or 
Discontinuation = Failure) for the intent-to-treat exposed (ITT-E) population.
Secondary efficacy endpoints will include: the proportion of subjects with plasma HIV-1 
RNA <50 c/mL and <400 c/mL over time; absolute values and change from Baseline in 
plasma HIV-1 RNA over time; absolute values and changes from Baseline in CD4+ cell 
counts over time, and incidence of disease progression (HIV-associated conditions, AIDS 
and death).
Safety endpoints will include: incidence and severity of adverse events (AEs) and 
laboratory abnormalities; the proportion of subjects who discontinue treatment due to 
AEs; absolute values and changes over time in laboratory parameters; change from 
Baseline in fasting lipids and glucose; changes from Baseline in renal and bone markers. 


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Heath outcomes endpoints will include: Change from Baseline in health related quality of 
life using SF-12 at Week 48, and treatment satisfaction (using the HIV Treatment 
Satisfaction Questionnaire) for subjects treated with DTG/ABC/3TC FDC and those 
treated with ATV+RTV+TDF/FTC FDC at weeks 4, 12, 24, and 48 (or withdrawal from 
the study).
Virology endpoints will include the incidence of treatment emergent genotypic and 
phenotypic resistance in subjects who meet confirmed virologic withdrawal criteria.


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1.
INTRODUCTION
1.1.
Background
Integrase inhibitors (INIs) are a relatively new class of antiretroviral drugs designed to 
block the action of the integrase viral enzyme, which catalyzes several key steps in the 
human immunodeficiency virus type 1 (HIV-1) life cycle and is responsible for insertion 
of the viral genome into the DNA of the host cell. Since integration is a vital step in 
retroviral replication, it is an attractive target for HIV therapy.  The first HIV INI, 
raltegravir (RAL, [Isentress Package Insert, 2013; Isentress, Summary of Product 
Characteristics, 2013]), was approved by the US Food and Drug Administration (FDA) 
and European Medicines Agency (EMA) in 2007.  Elvitegravir (ELV), another HIV INI, 
was approved by the US FDA in 2012 as part of a single tablet regimen (STR) with 
cobicistat (COBI), tenofovir (TDF), and emtricitabine (FTC, [Stribild Package Insert, 
2012]).  
While RAL and ELV have shown potent antiviral activity in treatment-naïve and 
treatment-experienced patients, there are limitations to both these medications.  Clinical 
resistance to both RAL and ELV has been reported from Phase II studies in treatment-
experienced patients [Hazuda, 2007; McColl, 2007] and from Phase III studies in both 
treatment-experienced [Cooper, 2008; Molina J, 2012] and treatment-naïve subjects 
[Lennox, 2010; Sax, 2012; DeJesus, 2012].  In addition, RAL requires twice daily (BID) 
dosing and is currently not available in a fixed dose combination (FDC) regimen. ELV 
requires co-administration with a pharmacokinetic (PK) booster, such as ritonavir (RTV) 
or COBI. Furthermore, ELV-containing regimens had higher rates of gastrointestinal (GI) 
adverse events (AEs) than a RAL-containing regimen and Atripla (a FDC of efavirenz 
[EFV]/TDF/FTC [Atripla, April 2013]) in treatment-experienced and treatment-naïve 
patients, respectively [Molina J, 2012; Sax, 2012]; Stribild is also not recommended for 
patients with creatinine clearance (CrCL) under 70 mL/min.  Because of the cobicistat in 
Stribild, there are also numerous drug interactions due to inhibition of cytochrome P450 
3A4. Therefore, development of new INIs with an improved safety and resistance profile, 
and improved dosing administration is desirable.
Dolutegravir (DTG) is a next-generation INI with low-moderate inter-subject 
pharmacokinetic variability, a predictable exposure-response relationship and a 14-hour 
plasma half-life that supports once daily dosing without the need for the PK boosters that 
are required with ELV (and therefore lacks the associated drug interactions, specifically 
with oral contraceptives).  
To date, the efficacy, pharmacokinetics, safety and drug interaction potential of DTG 
have been evaluated in an extensive program of Phase I to III clinical trials. Data are 
summarized in the DTG Investigator Brochure (IB [GlaxoSmithKline Document Number
[GSK Document Number RM2007/00683/11, GSK Document Number
2017N352880_00, GSK Document Number 2017N352880_01]).  In both antiretroviral 
therapy (ART)-naïve and ART-experienced (INI- naïve) patients, the safety profile for 
DTG 50 mg once daily was comparable to RAL and generally favorable to Atripla and 
EFV (studies ING113086 [SPRING-2], ING114467 [SINGLE] and ING111762 


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[SAILING]). The most frequently observed AEs across patient populations were 
diarrhea, nausea, and headache, which were generally Grade 1 or 2 in severity, and 
typically did not lead to discontinuation from studies.  With regards to antiviral efficacy, 
in treatment-naïve HIV-infected adult subjects, DTG 50 mg once daily was shown to be 
an efficacious dose, and non-inferior to RAL in combination with a background regimen 
with dual nucleoside reverse transcriptase inhibitor (NRTI) [SPRING-2]. When used in 
combination with abacavir/lamivudine (ABC/3TC, EPZICOM/KIVEXA™), DTG was 
shown to be superior to EFV/TDF/FTC, a result driven by better tolerability of the DTG 
based regimen [SINGLE].  Phase III studies have also demonstrated excellent antiviral 
activity of DTG in INI-naïve treatment experienced patients, and in patients with INI 
resistance in studies ING111762 [SAILING] and ING112574 [VIKING-3], respectively.  
Furthermore, DTG 50 mg once daily may have a higher barrier to resistance in INI-naive 
patients, as suggested in the treatment-experienced (INI-naive) SAILING study where 
significantly fewer virologic failures and significantly fewer subjects with INI resistance 
were observed when compared with RAL. Data from two further Phase III studies 
[SPRING-2 and SINGLE] in treatment-naive subjects are also supportive of a high 
barrier to resistance. 
HIV continues to be the leading cause of death and disease among women of 
reproductive age worldwide, particularly among women of ethnic/racial minorities.  
While women comprise approximately 50% of patients infected with HIV globally, the 
number of women in most HIV clinical trials remains low, and recruiting and retaining 
women into antiretroviral clinical studies remains a challenge.  The reasons are multiple, 
but may reflect differences in lifestyle, care commitments, behavior and socioeconomics 
between women and men infected with HIV.  Additionally, comparator regimens in many 
studies do not include commonly recommended regimens for women of child bearing 
potential, so pregnancy avoidance strategies are stringent.  
In Phase IIIa studies of DTG in treatment naïve subjects, women comprised 15% and 
16% respectively of the randomized populations in the SPRING-2 and SINGLE studies, 
for a total of 130 women randomized to DTG.  In the SPRING-2 study, DTG was non-
inferior to RAL overall and similar efficacy was observed across gender.  In the SINGLE 
study, DTG+ABC/3TC FDC demonstrated superior efficacy to EFV/TDF/FTC, and the 
treatment differences by gender were consistent with the overall treatment difference.  
The GRACE study is the only prospective clinical study with published data to date 
powered to assess gender differences in efficacy and safety [Currier 2010].  In this study 
of darunavir and RTV (DRV+RTV) in combination with optimized background therapy 
in ART-experienced subjects, the virologic response rate was lower in women than in 
men, and women had significantly higher rates of discontinuation (33%) compared to 
men (23%).  Nausea and vomiting was also more common in women.  Other non-
powered studies have seen increased rates of discontinuation and AEs in women 
compared to men (e.g., the CASTLE study [Molina, 2008]).
Evaluation of the safety, tolerability and efficacy of antiretroviral agents in women is 
important to appropriately inform clinicians and patients about their therapy.  Women 
may metabolize and respond to antiretroviral agents differently than men; women may 
have higher drug exposure, be at greater risk for some adverse events (i.e., lactic acidosis, 


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hepatotoxicity/rash, and osteoporosis), and have a higher potential for drug interactions 
(i.e., oral hormonal contraceptives/or estrogen).
FDCs and STRs have greatly simplified the treatment of patients with HIV, and may be 
of greater importance in patients with lifestyles or care commitments that may impair 
adherence to dosing schedules, including some women and those in underserved 
populations.  In a study by Paterson et. al. [Paterson, 1999], a linear relationship between 
levels of adherence and viral load suppression was observed. Adherence to therapy is 
essential to achieve viral suppression and prevent emergence of resistance mutations. 
Among regimens of comparable efficacy, physicians and HIV-1 infected patients who 
receive ART rate total pill burden, dosing frequency, and safety concerns among the 
greatest obstacles to achieving adherence. Drug resistant virus eventually emerges in 
most patients who struggle with consistent adherence. To achieve successful long-term 
treatment, the prevention of drug resistance has become the most significant challenge. 
DTG/ABC/3TC FDC is being developed to address the needs for a FDC with an INI and 
ABC/3TC.
1.2.
Rationale
The DTG/ABC/3TC FDC may provide a better treatment option for women infected with 
HIV-1 due to its robust antiviral activity, safety profile, high barrier to resistance, low 
potential for drug-drug interactions, and administration as a once-daily STR. Currently 
available integrase inhibitors, ELV and RAL, have limitations including the development 
of clinical resistance, the need for a BID regimen for RAL administration, and a PK 
booster for ELV administration, which leads to an increased potential for drug-drug 
interactions including with oral contraceptives.  Only limited data on DTG in women are 
available in Phase III studies due to lower enrollment of women compared with men. 
Therefore, a powered study of DTG in a STR with ABC and 3TC will be conducted in 
women to provide robust data on safety and efficacy in this population.  
Study ING117172 is a Phase IIIb trial designed to demonstrate the non-inferior antiviral 
activity of DTG/ABC/3TC FDC once daily to atazanavir plus ritonavir (ATV+RTV) and 
TDF/FTC FDC all administered once daily in HIV-1 infected, ART-naïve women over 
48 weeks.  This study will also characterize the safety and tolerability of DTG/ABC/3TC 
FDC compared to ATV+RTV+TDF/FTC FDC.  
The rationale for selection of the active comparator, ATV+RTV with TDF+FTC, is 
provided in the Section 3.2.
1.2.1.
Principle of Dose Selection
Dose selection was determined in ING112276 (SPRING-1). This was a dose-ranging 
Phase IIb study to evaluate the long-term antiviral activity and safety of DTG at doses of 
10, 25, and 50 mg once daily in combination with two NRTIs in HIV-infected, treatment-
naïve adult subjects. The dose selection strategy for DTG was to select the maximum 
tolerated dose from this study to take forward in to further evaluation in INI-naive 
subjects. If comparable efficacy, safety and tolerability were observed across all three 
DTG doses, the 50 mg dose would be selected for further investigation in Phase III.  


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Based on comparison of virological markers of HIV infection in the SPRING-1 study, the
proportion of subjects who achieved the primary endpoint (HIV-1 RNA <50 copies/mL 
[c/mL], by Time to Loss of Virologic Response [TLOVR] algorithm) by Week 16 was 
consistently high across the DTG dose arms (≥90%) with a low rate of confirmed 
virologic failure.  As summarized in the DTG IB, this activity has been maintained in all 
three dosing arms through Week 96 [GSK Document Number RM2007/00683/11, GSK 
Document Number 2017N352880_00, GSK Document Number 2017N352880_01].  
DTG was well tolerated across all doses studied. A good safety and tolerability profile 
with a low discontinuation rate due to AEs was observed in all three dose arms with no 
significant dose-dependent trends in safety parameters. Hence, the DTG 50 mg once daily 
dose was selected for Phase III studies in treatment-naïve adult subjects.
The efficacy and safety of DTG 50mg once daily was confirmed in the Phase III 
program.
1.2.2.
Impact of Potential Drug-Drug Interaction
Due to a different route of elimination, no drug interaction is expected between DTG and 
ABC/3TC.  DTG is metabolized through UGT1A1.  3TC is primarily eliminated by renal 
mechanisms with the majority of drug eliminated unchanged in the urine.  ABC is 
metabolized by glucuronidation and by alcohol dehydrogenase with less than 2% 
excreted in the urine as unchanged parent.  ABC does not have inhibitory activity on 
UGT pathways and is metabolized primarily through UGT2B7.  Only 25-36% of ABC is 
glucuronidated, indicating it is not a substrate sensitive route.  Furthermore, UGT is a 
high capacity enzyme system and the fraction metabolized by UGT pathways for both of 
these compounds is likely less than 50%.  Finally, no differences in DTG PK were 
observed for subjects receiving TDF/FTC versus ABC/3TC in SPRING-1 (ING112276).
For further information refer to the most current version of the IB for DTG [GSK 
Document Number RM2007/00683/11, GSK Document Number 2017N352880_00, GSK 
Document Number 2017N352880_01].  Relevant data on use of calcium and iron 
supplements with DTG are provided below.
1.2.2.1.
Use of calcium and iron supplements with dolutegravir
Study ING116898 was a Phase I, open label, randomized, four-period crossover study to 
evaluate the effects of calcium carbonate (CC) 1200 mg and ferrous fumarate (FF) 
325 mg on PK of DTG 50 mg in healthy adult subjects. 
Study Design: 12 subjects were enrolled into one of the two cohorts and received each of 
four treatments in a randomized fashion: 1) A single dose of DTG 50 mg administered 
under fasted conditions; 2) A single dose of DTG 50 mg co-administered with a single 
dose of CC 1200 mg or FF 324 mg under fasted conditions; 3) A single dose of DTG 
50 mg co-administered with a single dose of CC or FF with a moderate-fat meal; 4) A 
single dose of DTG 50 mg administered under fasted conditions 2 hours prior to 
administration of a single dose of CC or FF. There was a washout period of at least 


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7 days between treatments. Serial PK samples were collected during each treatment 
period for the measurement of plasma DTG concentrations.
Results: Under fasted conditions, co-administration of CC reduced DTG exposure by 37-
39% and FF reduced DTG exposure by 54-57%; food (a moderate fat meal) and 2 hour 
separation completely eliminated the negative effect of calcium carbonate on DTG 
exposure. 
Table 1
Statistical Comparison of Plasma DTG Pharmacokinetic Parameters 
(Calcium Carbonate Cohort)
Comparison
Ratio of GLS Means (90% CI)
DTG + CC vs DTG 
Alone (fasted)
DTG + CC (fed) vs 
DTG Alone (fasted)
DTG 2hr prior to 
CC vs DTG Alone 
(fasted)
DTG + CC (fed) vs 
DTG+ CC (fasted)
AUC(0-t)
0.61 (0.48, 0.79)
1.10 (0.84, 1.43)
0.95 (0.73, 1.24)
1.79 (1.37, 2.33)
AUC(0-)
0.61 (0.47, 0.79)
1.09 (0.84, 1.43)
0.94 (0.72, 1.23)
1.78 (1.36, 2.33)
Cmax
0.63 (0.50, 0.81)
1.07 (0.83, 1.38)
1.00 (0.78, 1.29)
1.70 (1.32, 2.18)
C24
0.61 (0.47, 0.80)
1.08 (0.81, 1.42)
0.90 (0.68, 1.19)
1.76 (1.33, 2.33)
CI = confidence interval
Table 2
Statistical Comparison of Plasma DTG Pharmacokinetic Parameters 
(Ferrous Fumarate Cohort)
Comparison
Ratio of GLS Means (90% CI)
DTG + FF vs DTG 
Alone (fasted)
DTG + FF (fed) vs 
DTG Alone (fasted)
DTG 2hr prior to FF 
vs DTG Alone 
(fasted)
DTG + FF (fed) vs 
DTG+ FF (fasted)
AUC(0-t)
0.45 (0.37, 0.54)
0.98 (0.81, 1.19)
0.94 (0.78, 1.14)
2.18 (1.80, 2.64)
AUC(0-)
0.46 (0.38, 0.56)
0.97 (0.80, 1.19)
0.95 (0.78, 1.15)
2.12 (1.75, 2.58)
Cmax
0.43 (0.35, 0.52)
1.03 (0.85, 1.26)
0.99 (0.81, 1.21)
2.40 (1.97, 2.94)
C24
0.44 (0.36, 0.54)
0.99 (0.80, 1.22)
0.92 (0.74, 1.13)
2.25 (1.83, 2.77)
Conclusions: DTG can be given concurrently with calcium or iron supplements with 
food; without food, DTG should be given 2 hours prior to or 6 hours after calcium or iron 
supplements. 
1.3.
Benefit:Risk Assessment
Summaries of findings from both clinical and non-clinical studies conducted with DTG 
can be found in the most current version of the DTG IB.  The following section outlines 
the risk assessment and mitigation strategy primarily for DTG in the DTG/ABC/3TC 
FDC in this protocol.  For ABC, 3TC, ATV, RTV and TDF/FTC, the approved country 
product labels should be referenced.  The comparator regimen, ATV+RTV + TDF/FTC 
FDC, is a preferred/recommended treatment regimen for HIV-infected ART naive 
subjects according to current guidelines [DHHS, 2013; EACS, 2012].


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1.3.1.
Risk Assessment
There are no shared metabolism pathways between the components of DTG/ABC/3TC, 
and no common target organs were identified in respective pre-clinical studies.  As such, 
there is no pharmacologic data that would predict increased safety risk for the 
DTG/ABC/3TC formulation beyond that identified for the individual active moieties 
DTG, ABC and 3TC.  Early in clinical development, no drug-drug interaction between 
DTG and ABC/3TC was apparent given the safety and efficacy profile observed in the 
Phase IIb study ING112276 [SPRING-1] in which 67 subjects received DTG in 
combination with ABC/3TC for up to 96 weeks.  Clinical safety data from the subjects 
treated with DTG + ABC/3TC in the pivotal ING114467 [SINGLE] and supporting study 
ING113086 were consistent with the safety profile of the individual active moieties.
All medications have AE profiles that must be assessed prior to use, allowing for an 
appropriate risk/benefit assessment.  Considerations when using DTG/ABC/3TC are as 
follows:


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Potential Risk 
of Clinical 
Significance
Data/Rationale for Risk
Mitigation Strategy1
Investigational Product (IP) [DTG/ABC/3TC] 
Refer to IB for additional information on DTG and DTG/ABC/3TC
Refer to approved country product label for additional information on ABC/3TC
Hypersensitivity 
(including abacavir 
hypersensitivity 
reaction [ABC 
HSR]) and rash
A well characterised, idiosyncratic, drug-related HSR is the most important risk 
associated with ABC (Section 6.4.4.9).  Exclusion of individuals found to carry 
the Human Leukocyte Antigen (HLA)-B*5701 allele from ABC therapy reduces 
the risk of HSR.  Rash, including Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) and Erythema Multiforme have been reported in 
patients taking ABC (See Section 6.4.4.9 and Section 6.4.4.10).  
HSR has been observed uncommonly with DTG.  Rash was commonly reported 
in DTG Phase IIb/III clinical trials; episodes were generally mild to moderate in 
intensity; no episodes of severe rash, such as SJS, TEN and Erythema 
Multiforme were reported.  Data on HSR for DTG and DTG+ABC/3TC FDC 
suggest that there will not be additional risk from HSR in HLA-B*5701 negative 
subjects receiving the DTG/ABC/3TC FDC
Subjects positive for HLA-B*5701 are excluded from participating.  
Additionally, subjects with history of allergy/sensitivity to any of the study 
drugs are excluded (Section 4.3).
Specific/detailed toxicity management guidance is provided for suspected 
HSR with DTG (Section 6.4.4.8) or ABC (Section 6.4.4.9), and skin 
reactions without systemic involvement (Section 6.4.4.10).
The subject informed consent form includes information on this risk and 
the actions subjects should take in the event of a HSR or associated signs 
and symptoms.  Subjects are to be reminded to read the ABC HSR 
Warning Card accompanying their study medication and of the importance 
of keeping this card with them at all times.
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. 
Current treatment guidelines [DHHS, 2013; EACS 2012] do not recommend 
monotheraphy with 3TC for patients with HBV infection, which is what subjects 
randomized to DTG/ABC/3TC would effectively be receiving.  Additionally, 
discontinuation of 3TC in HBV coinfected subjects can result in severe 
exacerbations of HBV. 
Subjects meeting either of the following criteria during the screening period 
are excluded from participating (Section 4.3).

Alanine aminotransferase (ALT) 5 times the upper limit of normal 
(ULN) or ALT 3xULN and bilirubin 1.5xULN (with >35% direct 
bilirubin)

Subjects positive for HBV at screening (hepatitis B virus surface 
antigen positive [+HBsAg]), or with an anticipated need for HCV 
therapy during the study
Specific/detailed liver stopping criteria and toxicity management guidance 
is provided for suspected DILI or other clinically significant liver chemistry 
elevations (Section 6.4.4.1).  


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Potential Risk 
of Clinical 
Significance
Data/Rationale for Risk
Mitigation Strategy1
Theoretical serious 
drug interaction with 
dofetilide
Co-administration of DTG may increase dofetilide plasma concentration via 
inhibition of OCT2 transporter, resulting in potentially life-threatening toxicity. 
The co-administration of DTG with dofetilide is prohibited in the study 
(Section 5.6.2).
GI intolerance
Non-clinical studies showed upper and lower GI toxicity, including vomiting, 
diarrhea and gastric erosions observed in monkey toxicology studies (thought to 
be related to local and not systemic toxicity).  
Mild to moderate GI intolerance (mainly diarrhea and nausea) is associated with 
DTG treatment in a small proportion of subjects; however there were no 
indications of an increased risk for peptic ulcers or serious erosions.
Routine monitoring of GI symptoms will be performed.
Renal function
Mild elevations of creatinine have been observed with DTG which are related to 
a likely benign effect on creatinine secretion with blockade of OCT-2 receptor.  
DTG has been shown to have no significant effect on glomerular filtration rate 
(GFR) or effective renal plasma flow. Measurement of albumin/creatinine ratio 
confirmed there was no difference in the effect of DTG on albumin excretion 
compared with EFV or RAL. 3TC is eliminated by renal excretion and exposure 
increases in patients with renal dysfunction. 
Due to requirements for dose reduction of 3TC in patients with renal 
dysfunction, subjects with a CrCL <50 mL/min are excluded (Section 4.3).
Specific/detailed toxicity management guidance is provided for subjects 
who develop a decline in renal function (including proximal renal tubule 
dysfunction; Section 6.4.4.6) and/or proteinuria (Section 6.4.4.7).  
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 EFV/TDF/FTC  in ING114467; however, this was 
not duplicated in any other Phase IIb/III study conducted with DTG.  
Subjects who in the investigator’s judgment, poses a significant suicidality 
risk, are excluded from participating (Section 4.3).
Because of the elevated risk in the HIV- infected population, treatment 
emergent assessment of suicidality will be monitored during this study.  
Investigators are advised to consider mental health consultation or referral 
for subjects who experience signs of suicidal ideation or behavior (Section 
6.4.10).
Creatine 
Phosphokinase 
(CPK)  elevations
Asymptomatic CPK elevations mainly in association with exercise have been 
reported with DTG therapy.  .
Specific detailed toxicity management guidance is provided for subjects 
who develop Grade 3 to 4 CPK elevations (Section 6.4.4.5).


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Potential Risk 
of Clinical 
Significance
Data/Rationale for Risk
Mitigation Strategy1
Increased 
occurrence of 
Immune 
reconstitution 
inflammatory 
syndrome (IRIS)
With rapid HIV-1 RNA decline and early recovery of CD4+ cell counts there 
could theoretically, be an increase in cases of IRIS.
The increased risk for HBV and HCV IRIS with DTG- containing ART is 
addressed above; there was a low rate of other medical conditions frequently 
implicated in IRIS cases.  
Subjects positive for HBsAb at screening or with active HCV illness 
(anticipated to require therapy) are excluded from participating. Subjects 
will have routine laboratory monitoring 
Use in pregnancy
The safe use of DTG in human pregnancy has not been established.  DTG has 
been shown to cross the placenta in reproductive toxicity studies in animals.  
DTG has not been associated with findings in animal reproductive studies. 
Women who are pregnant will be excluded from the study (Section 4.3).
Females of childbearing potential are required to have a negative 
pregnancy test at both Screening and Day 1 of the study and agree to use 
one of the methods documented in Section 4.2. to avoid pregnancy during 
the study.  Females of childbearing potential will have pregnancy tests 
performed at all scheduled clinic visits.  Pregnant women will be withdrawn 
from this study and their pregnancy followed to determine outcome 
(including premature termination) and status of mother and child.  
DTG: Neural tube 
defects
In one ongoing birth outcome surveillance study in Botswana, early results from 
an unplanned interim analysis show that 4/426 (0.9%) of women who were 
taking DTG when they became pregnant had babies with neural tube defects 
compared to a background rate of 0.1%.
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 6, Section 11.6), until at least 2 weeks after 
discontinuation of IP
2. Women who are breastfeeding or plan to become pregnant or 
breastfeed during the study are excluded;
3. Women who become pregnant, or who desire to be pregnant while in 
the study, or who state they no longer are willing to comply with the 
approved pregnancy avoidance methods, will have study treatment 
discontinued and withdrawn from the study.
4. Females of reproductive potential are reminded re: pregnancy 
avoidance and adherence to contraception requirements at every 
study visit.
5. Pregnancy status is monitored at every study visit


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1. Careful monitoring of events will be conducted using serious adverse event (SAE) reports and alerts for Grade 3/4 laboratory toxicities (per Division of Acquired Immunodeficiency 
Syndrome [DAIDS] toxicity gradings for HIV infected patients). Serious/severe events will be managed appropriately including, but not limited to, withdrawal of investigational 
product (IP), and will be followed to resolution as per Sponsor’s standard Medical Monitoring practices  Clinical Safety Data will be routinely reviewed in GlaxoSmithKline (GSK) 
Safety Review Team meetings. This will include in-stream review of data from this clinical trial on approximately a  monthly basis (switching to approximately quarterly reviews upon 
reaching the primary endpoint); review of aggregate data on a protocol and program basis when available; and review of competitor data from the literature


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1.3.2.
Benefit Assessment
The DTG/ABC/3TC FDC provides a convenient once daily STR, without need for a PK 
booster or food/fluid restrictions, and with limited safety implications resulting from 
theoretical or actual drug: drug interactions compared to other antiretroviral agents 
(including EFV and those requiring a PK booster).  
A regimen comprised of DTG administered with ABC/3TC has been shown to be highly 
efficacious and well tolerated in treatment-naive subjects.  In the Phase 3 double-blind 
SINGLE study (ING114467), 833 therapy-naive adults were randomized to DTG 50 mg 
plus ABC/3TC once daily or a guidelines-preferred STR of EFV/TDF/FTC once daily.  
At Week 48, the proportion of subjects with HIV-1 RNA <50 c/mL in the 
DTG+ABC/3TC arm (88%) was superior to the EFV/TDF/FTC arm (81%), P=0.003.  
Time to viral suppression (median 28 vs. 84 days; P<0.001) and increases in CD4 cell 
counts (+267.1 vs. +208.2 cells/mm3; P<0.001) also favored DTG+ABC/3TC. No 
subjects on DTG+ABC/3TC had detectable antiviral resistance; 1 TDF-associated and 4 
EFV-associated mutations were detected in EFV/TDF/FTC subjects with viral failure.  In 
a by gender analysis, Week 48 responses in women (85%) were higher in recipients of 
DTG + ABC/3TC when compared to EFV/TDF/FTC (75%). The overall proportion of 
subjects discontinuing for adverse events was lower with DTG+ABC/3TC (2%) than 
EFV/TDF/FTC (10%); rash and neuropsychiatric events (including abnormal dreams, 
anxiety, dizziness, and somnolence) were significantly more common on EFV/TDF/FTC, 
whereas insomnia was reported more frequently on DTG+ABC/3TC.  
Study participants may also benefit from the medical tests and screening procedures 
performed as part of the study.
1.3.3.
Overall Benefit:Risk Conclusion
Taking into account the measures taken to minimize risk to subjects participating in this 
study, the potential risks identified in association with the DTG/ABC/3TC FDC are 
justified by the anticipated benefits that may be afforded to women with HIV infection.
2.
OBJECTIVES
Primary Objective

To demonstrate the non-inferior antiviral activity of DTG/ABC/3TC FDC once daily
compared to ATV+RTV+TDF/FTC FDC each administered once daily over 48 
weeks in HIV-1 infected ART naïve women.
Secondary Objectives

To evaluate the antiviral and immunological activity and incidence of disease 
progression (HIV-associated conditions, AIDS and death) of DTG/ABC/3TC FDC 
once daily compared to ATV+RTV+TDF/FTC FDC once daily over time;


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
To compare the safety, tolerability, and laboratory parameters of DTG/ABC/3TC
FDC once daily to ATV+RTV+TDF/FTC FDC once daily over time;

To assess the development of viral resistance in subjects who meet confirmed 
virologic withdrawal criteria;

To evaluate renal markers (in urine and blood), and bone markers (in blood) in 
subjects treated with DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC;

To assess treatment satisfaction, and change in health-related quality-of-life for 
subjects treated with DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC;

To evaluate the effect of patient characteristics (i.e., demographic factors, HIV-1 
subtype, Baseline CD4) on response to DTG/ABC/3TC FDC compared to 
ATV+RTV+TDF/FTC FDC over time.
3.
INVESTIGATIONAL PLAN
3.1.
Study Design
This study is a 48 week Phase IIIb randomized, open-label, active-controlled, 
multicenter, parallel group, non-inferiority study. The study will be conducted in 
approximately 474 HIV-1 infected ART-naïve women. Subjects will be randomized 1:1 
to receive a DTG/ABC/3TC FDC 50mg/600mg/300mg once daily or ATV 
(300mg) +RTV (100mg) +TDF/FTC FDC (300mg/200mg) all administered once daily.  
The primary analysis will take place after the last subject completes 48 weeks on therapy. 
No dose reductions, modifications in dosage, or changes in the frequency of dosing will 
be allowed in this study.
The study design is summarized in Figure 1 and comprises the following Phases:
Screening Period
Randomization may occur as soon as all Screening procedures have been completed and 
results are available and on file. The 14-day screening period may be extended to 28 days 
to allow receipt of all Screening assessment results and to accommodate scheduling. 
Randomized Phase: Day 1 to Week 48
Subjects who fulfill eligibility requirements will be randomized 1:1 to receive 
DTG/ABC/3TC FDC once daily or ATV+RTV+TDF/FTC FDC each administered once 
daily.  In order to achieve balance across the two treatment groups of the study, 
randomization will be stratified by Screening plasma HIV-1 RNA (100,000 c/mL or 
>100,000 c/mL), and CD4+ cell count (350 cells/mm3 or >350 cells/mm3).  
During the Randomized Phase, subjects will attend the clinic at Baseline/Day 1 and at 
Weeks 4, 12, 24, 36 and 48 of treatment.  Additional contacts will be made at Weeks 8, 
18, 30 and 42 of treatment, primarily to confirm subjects’ understanding of the study 


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procedures and management of the treatment regimen; these contacts may be conducted 
via telephone, or as clinic or home visits (or other type of visit as agreed with GSK).
DTG/ABC/3TC FDC Continuation Phase
Subjects randomized to receive DTG/ABC/3TC FDC who successfully complete 48 
weeks of treatment will continue to have access to DTG/ABC/3TC FDC (Continuation 
Phase) until it is either locally approved and commercially available, the patient no longer 
derives clinical benefit, the patient meets a protocol-defined reason for discontinuation, 
or development of DTG/ABC/3TC FDC is terminated.  Subjects randomized to the 
ATV+RTV+ TDF/FTC arm will receive ATV+RTV+TDF/FTC FDC through their Week 
48 visit only, after which subjects will complete the study and will need to have alternate 
arrangements in place to access antiretroviral medication.
Study Completion
Subjects are considered to have completed the study if they satisfy one of the following:

Randomized to ATV+RTV+TDF/FTC FDC and completed the Randomized Phase 
including the Week 48 Study Visit;

Randomized to DTG/ABC/3TC FDC, completed the Randomized Phase including the 
Week 48 Visit, and did not enter the Continuation Phase;

Randomized to DTG/ABC/3TC FDC, completed the Randomized Phase, including 
the Week 48 study visit, entered and completed the Continuation Phase (defined as 
remaining on study until commercial supplies of DTG/ABC/3TC become locally 
available or development of DTG/ABC/3TC is terminated).
Follow Up
Subjects with ongoing AEs or laboratory abnormalities will attend a Follow-up visit 
approximately four weeks after their last dose of investigational product (DTG/ABC/3TC 
FDC or ATV+RTV+TDF/FTC FDC). Assessments at the Follow-up visit should reflect 
any ongoing complaints (e.g., blood draws to follow a laboratory abnormality). The 
Follow-Up visit is not required for successful completion of the study.


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Figure 1
Study Schematic
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. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM). The SPM will provide 
the site personnel with administrative and detailed technical information that does not 
impact subject safety.
3.2.
Discussion of Design
The design of this study (1:1 randomized, active-controlled, multicenter, parallel group) 
is well established for confirming the non-inferiority of an investigational agent 
compared to an active comparator and is generally accepted by regulatory authorities as 
rigorous proof of antiviral activity [CDER, 2002].
The primary endpoint, proportion of subjects at Week 48 with plasma HIV-1 RNA below 
the assay lower limit of detection (LLOD, i.e., <50 c/mL), is also a well-established 
surrogate endpoint for prognosis of HIV-1 infection and disease progression. 
Boosted protease inhibitors such as ATV+RTV are commonly used in women.  The use 
of ATV+RTV as the active comparator in therapy-naïve women is justified based on its 
indication as an appropriate agent as first line therapy in treatment-naïve HIV-1 infected 
adults, with specific data in HIV infected pregnant women [Reyataz Package Insert, 
2013].  ATV+RTV is recommended as a preferred first-line regimen in the treatment 
guidelines for women [DHHS, 2013; EACS, 2012; International AIDS Society (IAS), 
2010].  With other ART agents, there are concerns with regard to teratogenicity (e.g., 
efavirenz), drug-drug interactions with oral contraceptives (e.g., Stribild), or efficacy in 
patients with a viral load greater than 100,000 c/mL (e.g. Complera, a single tablet 
regimen of rilpivirine, TDF and FTC [Complera Package Insert, 2013]. Boosted PIs 


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possess a high genetic barrier to resistance, thus are commonly used in subjects at higher 
risk of virologic failure (e.g. patients with lifestyles or care commitments possibly 
impairing adherence to dosing schedules).
The open-label design best suits the objectives of this study, and is consistent with other 
pivotal studies that are included in the prescribing information for boosted protease 
inhibitors.  Blinding of the protease inhibitor component (particularly RTV, with its 
trademark embossed on the marketed tablet) is a substantial logistical hurdle.  ATV-
associated hyperbilirubinemia could also lead to unblinding of treatment arms. Moreover, 
in a double-dummy design, 4 pills per day would have to be administered to all subjects, 
which is burdensome and does not reflect a real life setting for subjects who may have a 
single tablet, once daily regimen available as a treatment option.  An open-label design
may enable assessment of the effect of pill burden upon patient treatment satisfaction, 
and virological outcome for subjects receiving one versus three pills once per day.
Dual NRTI therapy comprises the backbone of all first line HIV-1 ART according to 
global treatment guidelines, and both TDF/FTC and ABC/3TC are indicated for use in 
first line therapy globally.
Given the open-label design, study population and endpoints in this study, an 
Independent Data Monitoring Committee (IDMC) will not be implemented. The safety 
of DTG has been assessed in blinded studies during the Phase III program in which an 
IDMC was utilized and no issues were highlighted necessitating review of this study by 
an IDMC.
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA
4.1.
Number of Subjects
Sufficient subjects will be screened in order to ensure a total of approximately 474 
subjects will be randomized, approximately 237 to each study arm. Subjects will be 
enrolled from multiple geographic regions. 
Subjects
Screened
~675
Randomized
~474
Completed/Evaluable
~474
4.2.
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the GSK IP or other study treatment that may impact 
subject eligibility is provided in the IB, IB supplements, product labels, and/or local 
prescribing information.


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Deviations from inclusion 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. 
Subjects are allowed to re-screen for this study one time; this will require a new subject 
number. A single repeat test (re-test) per analyte or assessment is allowed during the
Screening period to determine eligibility (with the exception of a disqualified Screening 
genotype which may not be retested).
The following are study specific eligibility criteria unless stated otherwise.  In addition 
to these criteria, Investigators must exercise clinical discretion regarding selection of 
appropriate study subjects, taking into consideration any local treatment practices 
or guidelines and good clinical practice (GCP).  
Eligible subjects must:

be able to understand and comply with protocol requirements, instructions, and 
restrictions;

be likely to complete the study as planned;

be considered appropriate candidates for participation in an investigative clinical 
trial with oral medication (e.g. no active substance abuse, acute major organ, 
disease, or planned long term work assignments out of the country, etc.).  
Laboratory results from the central laboratory services provided by this trial will be used 
to assess eligibility.  If results from central laboratory services (e.g., hematology/ 
chemistry results) will delay screening beyond the defined 28 day period, use of local 
laboratory services may be used only after consultation and agreement with GSK.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. HIV-1 infected females (gender at birth) ≥ 18 years of age;
2. A female, may be eligible to enter and participate in the study if she: 
a. is of non-child-bearing potential either defined as post-menopausal (12 months of 
spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of 
becoming pregnant with documented tubal ligation, hysterectomy or bilateral 
oophorectomy or, 
b. is of child-bearing potential with a negative pregnancy test at both Screening and 
Day 1 and agrees to use one of the following methods of contraception to avoid 
pregnancy:

Refer to Appendix 6, Section 11.6: Modified List of Highly Effective 
Methods for Avoiding Pregnancy in Females of Reproductive Potential. 
Any contraception method must be used consistently, in accordance with the approved 
product label and for at least 2 weeks after discontinuation of IP.  The investigator is 
responsible for ensuring that subjects understand how to properly use these methods of 
contraception.


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All subjects participating in the study should be counseled on safer sexual practices 
including the use of effective barrier methods (e.g. male condom/spermicide).
3. HIV-1 infection as documented by Screening plasma HIV-1 RNA ≥500 c/mL;
4. Documentation that the subject is negative for the HLA-B*5701 allele;
5. Antiretroviral-naïve (10 days of prior therapy with any antiretroviral agent following 
a diagnosis of HIV-1 infection);
6. Signed and dated written informed consent is obtained from the subject or the subject’s 
legal representative prior to screening;
7. Subjects enrolled in France: a subject will be eligible for inclusion in this study only 
if either affiliated to or a beneficiary of a social security category.
4.3.
Exclusion Criteria
Deviations from 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. 
A single repeat test (re-test) per analyte is allowed during the Screening period (with the 
exception of a disqualifying Screening genotype which may not be retested).  
Subjects meeting any of the following criteria must not be enrolled in the study:
Exclusionary medical conditions
1.
Women who are pregnant or breastfeeding;
2.
Women who plan to become pregnant during the first 48 weeks of the study. 
3.
Any subject who has had a medical intervention for gender reassignment;
4.
Any evidence of an active Centers for Disease Control and Prevention (CDC) 
Category C disease (Section 11.1).  Exceptions include cutaneous Kaposi’s sarcoma 
not requiring systemic therapy and historic CD4+ cell counts of <200 cells/mm3.
5.
Subjects with any degree of hepatic impairment; 
6.
Subjects positive for hepatitis B (+HBsAg) at Screening, or anticipated need for 
HCV therapy during the study;
7.
History or presence of allergy to the study drugs or their components or drugs of 
their class;
8.
Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or 
resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial 
neoplasia; other localized malignancies require agreement between the investigator 
and the Study medical monitor for inclusion of the subject;


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9.
Subjects who in the investigator’s judgment, poses a significant suicidality risk. 
Recent history of suicidal behavior and/or suicidal ideation may be considered as 
evidence of serious suicide risk;
10. History of osteoporosis with fracture or requiring pharmacologic therapy with 
bisphosphonates (e.g., alendronate, ibandronate, risedronate, zoledronic acid), 
antiresorptive medications (e.g., denosumab, strontium ranelate, teriparatide), and 
estrogen receptor modulators (e.g., raloxifene, tamoxifen). Use of calcium and 
vitamin D is permitted.
Exclusionary Treatments prior to Screening or Day 1
11. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
12. Treatment with any of the following agents within 28 days of Screening: radiation 
therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter 
immune responses (a detailed list is provided in the SPM);
13. Treatment with any agent, except recognized ART as allowed above (Section 4.2), 
with documented activity against HIV-1 in vitro within 28 days of first dose of IP;
14. Exposure to an experimental drug or experimental vaccine within either 28 days,
5 half-lives of the test agent, or twice the duration of the biological effect of the test 
agent, whichever is longer, prior to the first dose of IP;
15. Subjects enrolled in France: the subject has participated in any study using an 
investigational drug during the previous 60 days or 5 half-lives, or twice the duration 
of the biological effect of the experimental drug or vaccine, whichever is longer, 
prior to screening for the study or the subject will participate simultaneously in 
another clinical study.
Exclusionary Laboratory Values or Clinical Assessments at Screening
16. Any evidence of primary viral resistance based on the presence of any major 
resistance-associated mutation [IAS USA, 2013] in the Screening result or, if known, 
any historical resistance test result. Note: retests of Screening genotypes are not
allowed;
17. Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid 
abnormalities (total cholesterol, triglycerides, High Density Lipoprotein (HDL) 
cholesterol, Low Density Lipoprotein (LDL) cholesterol). A single repeat test is 
allowed during the Screening period to verify a result); 
18. Any acute laboratory abnormality at Screening, which, in the opinion of the 
Investigator, would preclude the subject’s participation in the study of an 
investigational compound;
19. Alanine aminotransferase (ALT) 5 times the upper limit of normal (ULN), or 
ALT 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin);
20. Subject has CrCL of <50 mL/min via Cockroft-Gault method;
21. Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for 
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The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB).
Notwithstanding these minimum inclusion and exclusion criteria, Investigators must 
also follow country specific guidelines where they exist when making decisions about 
subjects who are eligible for study participation.
4.4.
Other Eligibility Criteria Considerations
To assess any potential impact on subject eligibility with regard to safety, the Investigator 
must refer to the DTG IB and supplements, approved product labels, and/or local 
prescribing information for detailed information regarding warnings, precautions, 
contraindications, AEs, drug interactions, and other significant data pertaining to the IPs.
4.5.
Withdrawal Criteria
Subjects permanently discontinuing study treatments prior to Week 48 are considered to 
be withdrawn from the study treatments and also from the study. Similarly, subjects in 
the DTG/ABC/3TC FDC arm who enter the Continuation Phase but permanently 
discontinue participation in the Continuation Phase prior to commercially available 
DTG/ABC/3TC FDC, are considered to be withdrawn from the study treatments and also 
from the study.
A subject may voluntarily discontinue participation in this study at any time. The 
Investigator may also, at their discretion, discontinue the subject from participating in this 
study at any time. Withdrawn subjects will not be replaced.
Subjects may be prematurely discontinued from the study for any of the following 
reasons:

Subject or Investigator non-compliance;

At the request of the subject, Investigator, or Sponsor;

The subject requires concurrent prohibited medications during the course of the 
study. The subject may remain in the study if in the opinion of the Investigator and 
the medical monitor, such medication will not interfere with the conduct or 
interpretation of the study or compromise the safety of the subject.
Subjects must be discontinued from the study for any of the following reasons:

Virologic withdrawal criteria as specified in Section 4.5.1 are met.

Subject requires substitution or dose modification of DTG, ABC, 3TC, ATV, RTV 
TDF or FTC;

Liver toxicity where stopping criteria specified in Section 6.4.4.1 are met and no 
compelling alternate cause is identified;


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
Grade 4 clinical AE considered causally related to IP (See Section 6.4.3);

Renal toxicity as specified in Section 6.4.4.6 and Section 6.4.4.7 are met and no 
compelling alternate cause is identified;

Clinically suspected ABC HSR as described in Section 6.4.4.9.

Rash criteria as described in Section 6.4.4.10 are met and no compelling alternate 
cause is identified.

Pregnancy (intrauterine), regardless of termination status of pregnancy. As a 
reminder, females of reproductive potential who changed their minds and desire to 
be pregnant, or who state they no longer are willing to comply with the approved 
pregnancy avoidance methods, should also be withdrawn from the study.
If a subject is prematurely or permanently withdrawn from the study, perform the 
procedures described in the Time and Events Table (Section 6.1) for the Withdrawal visit 
and if necessary the Follow Up visit. All data from the Withdrawal visit will be recorded, 
as they comprise an essential evaluation that should be done prior to discharging any 
subject from the study.  A Follow-up visit may occur approximately 4 weeks after the last 
dose of study treatment and is only required in subjects with ongoing clinical or 
laboratory AEs at the time of Withdrawal.
Should a subject fail to attend the clinic for a required study visit, the site should attempt 
to contact the subject and re-schedule the missed visit as soon as possible.  The site 
should also 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 based on previous non-compliance.  In cases where the subject does not return for 
the rescheduled visit or cannot be reached to reschedule the missed visit, the site should 
make every effort to regain contact with the subject (e.g. via telephone calls and/or 
sending a certified letter to the subject’s last known mailing address) so that they can 
appropriately be withdrawn from the study.  These contact attempts should be 
documented in the subject’s medical record.  Should the subject continue to be 
unreachable, then he/she will be considered to have withdrawn from the study with a 
primary reason of “Lost to Follow-up”.  For all other subjects withdrawing from the 
study, an alternative reason for discontinuation should be recorded in the electronic case 
report form (eCRF).
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 CRF. Every effort should be made by the 
Investigator to follow up subjects who withdraw from the study. In the event that a 
subject is prematurely discontinued from the study at any time due to an AE (see 
Section 6.4.3) the procedures stated in the Time and Events Table (Section 6.1) must be 
followed. Subjects who are withdrawn from the study will not be replaced. 
Subjects may have a temporary interruption to their study treatment for management of 
toxicities (Section 6.4.3).


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4.5.1.
Virologic Criteria for Subject Management and Viral 
Resistance Testing
Subjects with plasma HIV-1 RNA levels 50 c/mL at Week 24 or beyond must have 
HIV-1 levels re-assessed using the algorithms below (Figure 2 and Figure 3) which detail 
protocol defined clinical management for subjects who either require more careful
monitoring (meet “4 to 6 week HIV-1 RNA testing criterion”) or have met a 
“suspected or confirmed virologic withdrawal criterion”.  Investigators should not 
schedule re-assessment blood draws in the presence of factors that could be associated 
with virologic blips, such as intercurrent infection, treatment interruption due to toxicity 
management or non-compliance, or vaccination.  Subjects should have received full 
doses of IP for at least 2 weeks at the time of HIV-1 RNA re-assessment for any HIV-1 
RNA level 50 c/mL.


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Figure 2
Virologic Criteria for Subject Management at Week 24
Week 24 Visit
HIV-1 RNA is <50 c/mL
HIV-1 RNA is 50 c/mL but <400 c/mL
HIV-1 RNA is 400 c/mL
Maintain scheduled visit 
at Week 36
Perform an unscheduled visit in approximately 4-6 weeks 
to reassess plasma HIV-1 RNA
Subject has met “4 to 6 Week HIV-1 RNA Testing 
Criterion”
Proceed to Figure 3
Perform an unscheduled visit in approximately 
4-6 weeks to reassess plasma HIV-1 RNA
Subject has met “Suspected Virologic 
Withdrawal Criterion”
Proceed to Figure 3
Figure 3
Virologic Criteria for Subject Management after Week 24
Any Visit (scheduled or unscheduled) after Week 24
Current HIV-1 RNA <50 c/mL
Current HIV-1 RNA 50 but 
<400 c/mL
Current HIV-1 RNA ≥400 c/mL
Regardless of previous HIV-1 RNA 
result, proceed to next scheduled visit 
per Time and Events Table
Regardless of previous HIV-1 RNA 
result, perform an unscheduled visit 
in approximately 4-6 weeks to 
reassess plasma 
HIV-1 RNA*
Subject has met “4 to 6 Week 
HIV-1 RNA Testing Criterion”
If previous HIV-1 RNA was 
<400 c/mL, perform an unscheduled 
visit in approximately 4-6 weeks to 
reassess plasma HIV-1 RNA*
Subject has met “Suspected 
Virologic Withdrawal Criterion”
If previous HIV-1 RNA was 
400 c/mL, discontinue subject 
from study once resistance test 
results are available
Subject has met “Confirmed 
Virologic Withdrawal Criterion”
*If current visit is Week 48 scheduled visit, perform unscheduled visit in 2-4 weeks rather than 4-6 weeks for assessment of primary endpoint.


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If HIV-1 RNA level is ≥400 c/mL on two consecutive assessments, a plasma for storage 
sample from the “suspected virologic withdrawal criterion” visit will be used for HIV-1 
genotype/phenotype testing.  Subjects may continue to receive IP at the discretion of the 
Investigator until results of resistance testing are available at which time the subject must 
be discontinued from the study.  If a subject is prematurely discontinued from the study, 
the Investigator must make every effort to perform the evaluations outlined in the Time 
and Events Table (Section 6.1).  These data will be recorded as they comprise essential 
evaluations needed to be done before discharging any subject from the study.
Note: Plasma samples with <400 c/mL of HIV-1 RNA will not be analyzed, as the 
protease/reverse transcriptase/integrase assays used in this study are not validated for 
plasma HIV-1 RNA levels <400 c/mL.
4.6.
Screening Failures
A subject is considered a screen failure if after providing informed consent, the subject’s 
circumstances or conditions change or the outcome of a test or assessment becomes 
available which results in the subject’s failure to meet one or more of the entry criteria, or 
results in the investigator deciding that the subject is no longer an appropriate study 
candidate.
Subjects are allowed to re-screen for this study one time; this will require a new subject 
number. There is no timeline restriction for re-screening.  A single repeat test (re-test) per 
analyte or assessment is allowed during the screening period to determine eligibility (with 
the exception of a disqualified Screening genotype which may not be retested).  
Laboratory results from the central laboratory services provided by this trial will be used 
to assess eligibility.  If results from central laboratory services (e.g., chemistry or 
hematology results) will delay screening beyond the defined 28 day period, use of local 
laboratory services may be used only after consultation and agreement with GSK.
5.
STUDY TREATMENTS
5.1.
Investigational Product and Other Study Treatment
IP in this protocol refers to the investigational study drug DTG/ABC/3TC FDC and the 
comparator drugs ATV, RTV and TDF/FTC FDC.  All IP will be supplied by GSK.
Under normal conditions of handling and administration, investigational product is not 
expected to pose significant safety risks to site staff.  A Material Safety Data Sheet 
(MSDS) 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 
upon request.
Investigational product must be stored in a secure area under the appropriate physical 
conditions for the products.  Access to and administration of the investigational product 
will be limited to the investigator and authorized site staff.  Investigational product must 


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be dispensed or administered only to subjects enrolled in the study and in accordance 
with the protocol.
The contents of the label will be in accordance with all applicable regulatory 
requirements.
5.1.1.
Tablet Formulation of DTG/ABC/3TC FDC
DTG/ABC/3TC FDC tablets, 50 mg/600 mg/300 mg are purple, oval, biconvex tablets 
debossed with ‘572 Trı’ on one side and plain on the other side. The tablets contain 
52.6 mg dolutegravir sodium which is equivalent to 50 mg dolutegravir free acid, 702 mg 
abacavir sulphate which is equivalent to 600 mg abacavir and 300 mg lamivudine. The 
tablets are packaged into high density polyethylene (HDPE) bottles with child-resistant 
closures that include induction seals. The bottles contain a desiccant.  Tablets must be 
stored in the original package with the bottle tightly closed. Desiccants must be kept in 
the bottle to protect from moisture.
5.1.2.
Tablet Formulations of ATV, RTV, TDF/FTC FDC
Atazanavir (ATV [Reyataz] will be supplied by GSK as commercial product.  Each 
capsule contains 300 mg atazanavir as atazanavir sulphate.  Reyataz is manufactured by 
Bristol Myers Squibb.
Tenofovir disoproxil fumarate/ emtricitabine fixed dose combination (TDF/FTC FDC 
[Truvada]) will be provided by GSK as commercial product.  Each tablet of Truvada 
contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is 
equivalent to 245 mg of tenofovir disoproxil). Truvada is manufactured by Gilead 
Sciences. 
Ritonavir (RTV [Norvir] will be supplied by GSK as commercial product.  Each tablet 
contains 100 mg ritonavir. Norvir is manufactured by AbbVie Inc.
5.1.3.
Dosage and Administration
The study has an open-label design.  Details of dosing for both randomized arms are 
outlined in the following table:
Treatment Arm
Investigational Product
Dose and Dose Interval
DTG/ABC/3TC 
DTG/ABC/3TC FDC
1 x 50 mg/600 mg/300 mg tablet once daily
ATV+RTV+TDF/FTC
ATV
1x 300 mg capsule once daily
RTV
1 x 100 mg tablet once daily
TDF/FTC FDC
1 x 300 mg/200 mg tablet once daily
DTG/ABC/3TC FDC may be administered with or without food.  ATV+RTV+ TDF/FTC 
FDC must be taken with food.


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5.2.
Treatment Assignment
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment.
Subjects will be assigned to study treatment in accordance with the randomization 
schedule.  Randomization will be conducted via a central randomization procedure 
following confirmation of fulfillment of study entry criteria. Subjects will be assigned 
(1:1) to study treatment in accordance with the computer generated randomization 
schedule. The central randomization schedule, including stratification, will be generated 
using the GSK validated randomization software RANDALL. Study site personnel will 
be required to contact the central randomization service for assignment of a unique 
identifier (designating the subject’s randomization code) for each subject participating in 
the study. A unique treatment number will be assigned for each subject participating in 
the study.  Subjects will maintain the assigned treatment group throughout the 
Randomized Phase (up to Week 48) and if applicable the Continuation Phase (after Week 
48 for subjects randomized to the DTG/ABC/3TC arm).
Subjects who are randomized into the trial and subsequently withdrawn may not be re-
screened.
5.3.
Blinding
As this is an open-label study, blinding is not required.
5.4.
Product Accountability
In accordance with local regulatory requirements, the investigator, designated site staff, 
or head of the medical institution (where applicable) must document the amount of 
investigational product dispensed and/or administered to study subjects, the amount 
returned by study subjects, and the amount received from and returned to GSK, when 
applicable.  Product accountability records must be maintained throughout the course of 
the study.
5.5.
Treatment Compliance
Treatment compliance will be evaluated using pill counts of unused IP. This assessment 
will be conducted each time the subject receives a new (refill) supply of study medication 
through the Withdrawal visit or study completion. These data will be recorded in the 
subject’s CRF, but will not be summarized for analysis purposes.  
5.6.
Concomitant Medications and Non-Drug Therapies
Subjects 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 the study medications. All concomitant 


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medications taken during the study will be recorded in the CRF. The minimum 
requirement is that the drug name and the dates of administration are to be recorded.
5.6.1.
Permitted Medications and Non-Drug Therapies
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study (except prohibited medications described in 
Section 5.6.2).  Chemoprophylaxis for HIV-associated conditions is encouraged, if 
appropriate, at the discretion of the subject and their physician. All concomitant 
medications, blood products, and vaccines taken during the study will be recorded in the 
CRF with dates of administration.
Because non-HIV vaccines may cause a temporary increase in the level of HIV-1 plasma 
RNA, it is recommended that a vaccine, if necessary, be given during or immediately 
after a scheduled visit after all laboratory tests have been drawn. This approach will 
minimize the risk of non-specific increases in the level of HIV-1 plasma RNA at the next 
scheduled assessment.
DTG/ABC/3TC FDC should be administered 2 hours before or 6 hours after taking 
antacid products or sucralfate containing divalent cations (e.g. aluminum and 
magnesium). Proton pump inhibitors and H2-antagonists may be used in place of antacids 
with no scheduling restrictions. Concurrent administration with multivitamins is 
acceptable.
DTG/ABC/3TC FDC can be co-administered with calcium or iron supplements if taken 
with a meal. Under fasted conditions, DTG/ABC/3TC FDC should be given 2 hours prior 
to OR 6 hours after calcium or iron supplements.
Metformin concentrations may be increased by DTG. Subjects should be monitored 
during therapy and a metformin dose adjustment may be required.
5.6.2.
Prohibited Medications and Non-Drug Therapies
HIV immunotherapeutic vaccines are not permitted at any time during the study (see 
Section 5.6.1 for guidance regarding non-HIV vaccines). Other experimental agents, 
antiretroviral drugs not otherwise specified in the protocol, cytotoxic chemotherapy, or 
radiation therapy may not be administered (see Exclusion Criteria, Section 4.3). 
Systemically administered immunomodulators that directly affect immune responses are 
prohibited. HCV therapy during the study will not be permitted as approved HCV 
therapies at present includes interferon.
Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided; however, 
short treatment courses (for example, 10 days or less) and topical, inhaled, or intranasal 
use of glucocorticosteroids will be allowed.
Acetaminophen is not to be used in patients with acute viral hepatitis.
For a detailed list of prohibited medications, please consult the SPM.


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5.6.2.1.
Prohibited medications for subjects randomized to DTG/ABC/3TC FDC
For subjects randomized to DTG/ABC/3TC FDC, the following medications or their 
equivalents must not be administered concurrently:

barbiturates

carbamazepine

oxcarbazepine

phenobarbital

phenytoin

St. John’s wort

dofetilide

rifampin
Dofetilide is prohibited as DTG may inhibit its renal tubular secretion resulting in 
increased dofetilide concentrations and potential for toxicity.
Methadone - due to potential for decreased plasma concentrations, subjects should be 
monitored for signs of withdrawal and methadone dose adjusted as appropriate.
5.6.2.2.
Prohibited medications for subjects randomized to ATV+RTV + 
TDF/FTC FDC
For subjects randomized to ATV+RTV+TDF/FTC FDC, the following medications or 
their equivalents must not be administered concurrently:

alfuzosin

rifampin

irinotecan

triazolam

midazolam (oral)

dihydroergotamine

ergotamine

ergonovine

methylergonovine

cisapride

St John’s wort

lovastatin

simvastatin

pimozide

sildenafil
For information on concurrent therapies and interactions suspected to be relevant to other 
antiretroviral therapy in the regimen, please consult the local prescribing information.


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5.7.
Treatment after the End of the Study
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the patient’s medical condition whether or not GSK is providing specific 
post study treatment.
Subjects randomized to DTG/ABC/3TC FDC
To provide continued access to unapproved investigational drug to subjects deriving 
therapeutic benefit, subjects randomized to receive DTG/ABC/3TC FDC and who have 
successfully completed 48 weeks of treatment in the Randomized Phase will be given the 
opportunity to continue to receive DTG/ABC/3TC FDC until one of the following 
occurs:

DTG/ABC/3TC FDC is locally approved and commercially available,

The subject no longer derives clinical benefit from receipt of DTG/ABC/3TC FDC,

The subject meets a protocol-defined reason for discontinuation or

The development of DTG/ABC/3TC FDC is discontinued.
Subjects randomized to ATV+ RTV + TDF/FTC FDC
As subjects randomized to receive ATV+RTV+TDF/FTC FDC complete the Week 48 
visit in the Randomized Phase, they will complete the study.  Investigative sites must 
make arrangements for provision of ATV, RTV and FTC/TDF FDC or their 
individual components to all subjects early during the study to ensure subject access 
to medication post study. 
5.8.
Treatment of Study Treatment Overdose
Any tablet intake exceeding the randomized daily number of tablets for IP will be 
considered an overdose.
For the purposes of this study, an overdose is not an AE (Refer to Section 6.4.5.1) unless 
it is accompanied by a clinical manifestation associated with the overdose. If the clinical 
manifestation presents with serious criteria, the event is a SAE, see Section 6.4.5.2.
If an overdose occurs and is associated with an adverse event requiring action, all study 
medications should be temporarily discontinued until the adverse event resolves. 
The Investigator should use clinical judgment and also refer to the prescribing 
information for approved ARTs, as appropriate in treating overdose, as GSK is unable to 
recommend specific treatment.


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6.
STUDY ASSESSMENTS AND PROCEDURES
6.1.
Time and Events Schedule
Table 3
Time and Events Table
Procedures
Screena
Day 1
Randomized Phase
Continuation 
Phasek
Withdrawal
Follow-
upl
Clinic Visits
Contact at 
Wk 8 18, 
30, 42r
Every 12 
weeks after 
Week 48
Week
4
Week
12
Week
24
Week
36
Week
48
Clinical and Other Assessments
Written informed consent
X
Inclusion/Exclusion criteriab
X
X
Demography
X
Prior ART history
X
Medical historyc
X
Current medical conditions
X
HIV risk factors and mode of 
transmission
X
CDC HIV-1 classification
X
X
HIV associated conditions
X
X
X
X
X
X
X
Cardiovascular risk assessmentd
X
Columbia Suicidality Severity Rating 
Scale
Xu
X
X
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
Limited physical examinations
X
X
X
X
X
X
X
X
X
X
12-lead ECGt
X
Adverse events
X
X
X
X
X
X
X
X
X
X
Serious adverse events
Xj
X
X
X
X
X
X
X
X
X
X
SF-12w
X
X
X
X
HIVTSQw
X
X
X
X
X


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Procedures
Screena
Day 1
Randomized Phase
Continuation 
Phasek
Withdrawal
Follow-
upl
Clinic Visits
Contact at 
Wk 8 18, 
30, 42r
Every 12 
weeks after 
Week 48
Week
4
Week
12
Week
24
Week
36
Week
48
Confirm understanding of study  and 
management/tolerability of regimen
X
X
X
X
X
X
X
X
Laboratory Assessments
Plasma for HIV genotyping
X
Quantitative plasma HIV-1 RNA
X
X
X
X
Xn
Xn
Xn
Xn
X
Lymphocyte subset 
X
X
X
X
X
X
X
X
X
X
Plasma for storagee
X
X
X
X
X
X
X
X
X
X
HLA-B* 5701 testingq
X
Clinical chemistry
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
Fasting lipids and glucosef
X
X
X
X
X
Urinalysis and spot urine for protein 
analysisg
X
X
X
Xp
Xm
X
Pregnancy testh
S
U
S
S
S
S
S
S
S
HBsAg and hepatitis C antibody
X
Pharmacogenetic samplei
X
Bone marker analytes (blood)v
X
X
X
Investigational Product
IVRS
X
X
X
X
X
X
X
X
X
X
Dispense IP
X
X
X
X
X
Xo
X
IP accountability (pill counts)
X
X
X
X
X
X
X


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a.
The 14-day Screening period maybe extended to 28 days.  Randomization may occur as soon as all Screening results are available.
b.
Inclusion/exclusion criteria will be fully assessed at the Screening visit.  Changes between the screening visit and the Day 1 visit should be assessed to ensure eligibility, 
including additional assessments performed at Day 1.
c.
Full medical history will be collected. Targeted medical history assessments will include cardiovascular, metabolic (e.g., Type I or II DM), psychiatric (e.g, depression) and renal 
(e.g., nephrolithiasis, nephropathy, renal failure) disorders.
d.
Assessment for cardiovascular risk will include height, weight, blood pressure, smoking history, medical conditions, and family history of premature cardiovascular disease
e.
Plasma samples for storage will be collected at each visit for possible future analyses (including but not limited to HIV-1 RNA genotypic and phenotypic analyses, HIV-1 RNA 
levels, and immunological parameters).  These samples will be used when needed such as when samples are lost or arrive at the laboratory unevaluable.  Additionally, these 
samples will be used for genotypic and/or phenotypic analyses when subjects meet confirmed virologic withdrawal criteria (see Section 4.5.1).
f.
An overnight fast is preferred, however a minimum of a 6 hour fast is acceptable.
g.
A morning specimen is preferred.
h.
Pregnancy testing. Women of childbearing potential only. S=serum, U=urine.  Remind females of reproductive potential of the need to avoid pregnancy while in study and 
adherence to the study’s contraception requirements.
i.
Informed consent for optional pharmacogenetics (PGx) research must be obtained before collecting a sample. Collection of the PGx sample at Day 1 is preferred, however this 
sample may be collected at any time during the study.
j.
Only SAEs related to study participation or to a concomitantly administered GSK product will be collected between obtaining informed consent and administration of IP at Day 1.
k.
For subjects who completed randomized DTG/ABC/3TC FDC through Week 48 and entered into DTG/ABC/3TC FDC Continuation Phase: subjects completing the 
DTG/ABC/3TC FDC Continuation Phase must return to the clinic when transitioning to commercial supplies.  Conduct study assessments as specified per the Week 36 
schedule at this end of Continuation Phase visit.
l.
A Follow up visit may be conducted approximately 4 weeks after the last dose of study provided IP, and is required only if the subject has ongoing AEs or lab abnormalities at 
the last on study visit.  The assessments performed should reflect what is considered medically necessary to assess the event(s).
m.
Conduct assessments at Week 48 OR at the Withdrawal visit for subjects who discontinue from the study prior to Week 48, but not both.
n.
Beginning at Week 24, subjects with plasma HIV-1 RNA 50 but <400 c/mL who elect to remain in study must return every 4-6 weeks for collection of samples for HIV-1 RNA 
determination and plasma for storage. Genotype and phenotype testing will only be performed with confirmed HIV-1 RNA ≥400 c/mL.
o.
For subjects receiving DTG/ABC/3TC FDC in Continuation Phase only
p.
Will be tested every 24 weeks (not every 12 weeks)
q.
Documentation that the subject had been screened for, and is negative for the HLA-B*5701 allele is acceptable.
r.
Contacts at Week 8,18, 30 and 42 are mandatory but may be conducted as a telephone, clinic or home visit (or other type of visit as agreed with GSK).
s.
Limited physical examination to include blood pressure at Baseline (recorded in eCRF) for Framingham score assessment, and weight at each visit (recorded in eCRF at 
Baseline and on lab requisition at all visits) for determination of CrCL. Blood pressure to be measured after resting in a semi-supine position for at least 5 minutes.  
t.
A 12-lead electrocardiograph (ECG) will be performed after resting in a semi-supine position for at least 5 minutes.  
u.
On Day 1, the Columbia Suicidality Severity Rating Scale (conducted by voice response system) is to be administered prior to randomization.
v.
Blood sample for bone marker assessment.  Only the result for 25 hydroxy-vitamin D will be reported to the investigator.
w.
SF-12 and HIV Treatment Satisfaction Questionnaire (HIVTSQ) is recommended to be administered at the beginning of the visit. 


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6.2.
Critical Baseline Assessments
Written informed consent must be obtained from each potentially eligible subject (or 
his/her legal representative) by study site personnel prior to the initiation of any 
Screening procedures as outlined in this protocol. The consent form must have been 
approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). 
After signing an informed consent, subjects will complete Screening assessments to 
determine subject eligibility. Each subject being screened for study enrolment evaluation 
will be assigned a subject number. This number will be given sequentially in 
chronological order of subject presentation according to a numeric roster provided by 
GSK.
6.2.1.
Screening Assessments
Assessments to be conducted at Screening are provided in the Time and Events Table 
(Section 6.1).  
Eligible subjects may be randomized as soon as all Screening assessments are complete 
and the results are available and documented. All subjects will complete a Screening 
period of approximately 14 days prior to Baseline (Day 1) during which all clinical and 
laboratory assessments of eligibility must be performed and reviewed.  The Screening 
period may be extended to 28 days to accommodate availability of all Screening 
assessment results and scheduling.  All Screening results must be available prior to
randomization.
Eligibility criteria must be carefully assessed at the Screening visit.  Physical exams 
should be conducted as part of normal routine clinical care but will not be collected 
systematically in the CRF.
All subjects must have been screened and be negative for the HLA-B*5701 allele before 
randomization can take place.  Results must be available for source document 
verification.
All subjects must provide a plasma sample for determination of primary viral resistance 
based on the presence of any major resistance-associated mutation.  
Subjects who meet all entry criteria are randomized and assigned a randomization 
number. Subjects not meeting all inclusion and exclusion criteria at initial screen may be 
re-screened (with the exception of a disqualifying viral phenotype) and receive a new 
subject number one time.  Subjects who are randomized into the trial and subsequently 
withdrawn from the study for any reason, may not be re-screened.
6.2.2.
Baseline (Day 1) Assessments
Assessments to be conducted at Baseline (Day1) are provided in the Time and Events 
Table (Section 6.1). 
At Day 1 and prior to randomization, any changes to the eligibility parameters must be 
assessed and any results required prior to randomization (e.g. Day 1 urine pregnancy test 
for women of child bearing potential) must be available and reviewed.  


2 0 1 3 N 1 6 1 6 4 9 _ 0 3
C O N FI D E N TI A L
I NG 1 1 7 1 7 2
4 8
Car di o vasc ular me dical hist or y /ris k fact ors will be assesse d at Baseli ne, t o i ncl u de 
s m o ki n g stat us a n d hist or y a n d fa mil y hist or y of car diac e ve nts. 
6. 2. 3.
S u bj e ct s i nf e ct e d wit h H e p atiti s B ( H B V) a n d/ or H e p atiti s C ( H C V)
S u bjects i nfecte d wit h H B V or wit h a n a ntici pate d nee d f or H C V t hera p y d uri n g t he 
st u d y ma y n ot be e nr olle d i nt o t his st u d y. A p pr o ve d H C V t hera p y c urre ntl y i ncl u des t he 
pr o hi bite d me dica ti o n i nterfer o n.
6. 3.
Effi c a c y
6. 3. 1.
Effi c a c y  E val u ati o n s
Pl a s m a HI V -1 R N A
Plas ma f or q ua ntitati ve HI V- 1 R N A will be c ollecte d acc or di n g t o t he Ti me a n d E ve nts 
Ta ble ( Secti o n 6. 1 ).  Met h o ds t o be use d ma y i ncl u de b ut are not li mite d t o t he A b b ott 
Real Ti me HI V -1 Assa y  l o wer li mit of detecti o n ( L L O D) 4 0 c/ m L. 
 
L y m p h o c y t e S u b s et s
L y m p h oc y te s u bsets will be c ollecte d f or assess me nt b y fl o w c yt o metr y (t otal 
l ym p h oc y te c o u nts, perce nta ge a n d a bs ol ute C D 4 + l ym p h oc y te c o u nts) acc or di n g t o 
Ti me a n d E ve nts Ta ble ( Secti o n 6. 1 ).
HI V A s s o ci at e d C o n diti o n s
HI V- ass ociate d c o n diti o ns will be rec or de d as per Ti me a n d E ve nts T a ble.  HI V-
ass ociate d c o n diti o ns will be assesse d acc or di n g t o t he 1 9 9 3 C D C Re vise d Classificati o n 
S y ste m f or HI V I nfecti o n i n A d ults (A p pe n di x 1 , Secti o n 1 1. 1 ).  I n dicat ors of cli nical 
disease pr o gressi o n are defi ne d as:
C D C Cate g or y  A at e nr oll me nt
Cate g or y  C e ve nt;
C D C Cate g or y  B at e nr oll me nt
Cate g or y  C e ve nt;
C D C Cate g or y  C at e nr oll me nt
Ne w Cate g or y  C E ve nt;
C D C Cate g or y  A, B or C at e nr oll me nt 
Deat h.
6. 3. 2.
Pri m ar y  E n d p oi nt
T he pri mar y  e n d p oi nt f or t his st u d y will be t he pr o p orti o n of s u bjects wit h plas ma HI V- 1 
R N A < 5 0 c o pies/ m L at Wee k 4 8 usi n g t he S na ps h ot al g ori t h m ( Missi n g, S witc h or 
Disc o nti n uati o n = Fail ure) f or t he I T T-E p o p ulati o n (see Secti o n 8. 3. 3. 1 ).
C CI


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6.3.3.
Secondary Efficacy Endpoints

Proportion of subjects with plasma HIV-1 RNA <50 and <400 c/mL over time;

Absolute values and change from Baseline in plasma HIV-1 RNA over time;

Absolute values and changes from Baseline in CD4+ cell counts over time;

Incidence of disease progression (HIV-associated conditions, AIDS and death).
6.4.
Safety
6.4.1.
Safety Evaluations
Safety assessments will include the following:

Monitoring and recording all AEs and SAEs.  Additional information on the Time 
Period and Frequency of Detecting AEs and SAEs is provided in Section 6.4.12;

Regular monitoring of hematology, blood chemistry and fasting lipids (parameters to 
be tested listed in Table 4 below);

Physical exams should be conducted as part of normal routine clinical care but will 
not be collected systematically in the CRF.  Abnormalities noted during any exam 
must be recorded in the CRF (e.g., in the current medical conditions or AE logs);

Periodic assessment of urine/urinalysis parameters as described below;

Evaluation and documentation of all concomitant medications and blood products;

Suicidality monitoring using the Columbia Suicide-Severity Rating Scale (Section 
6.4.10).
Any appropriately qualified site personnel (e.g. Investigator, sub-Investigator or study 
coordinator/nurse) can perform assessments.  A central laboratory chosen by GSK will 
undertake all routine scheduled laboratory evaluations within the study.  Refer to the 
central laboratory manual for specific instructions on sample collection, processing, 
storage and shipping for each laboratory test.


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Table 4
Laboratory Assessments
Hematology
Platelet Count
Automated WBC Differential:
RBC Count
Neutrophils
WBC Count (absolute) 
Lymphocytes
Hemoglobin
Monocytes
Hematocrit
Eosinophils
MCV
Basophils
MCV = mean corpuscular volume, RBC = red blood cells, WBC = white blood cells
Clinical Chemistry
BUN
Potassium
AST
Total bilirubina
Creatinineb
Chloride
ALT 
Albumin 
Glucose
Total CO2
Alkaline phosphatase
Creatine phosphokinase
Sodium
Lipase
Phosphate
BUN = blood urea nitrogen
a.
Direct bilirubin will be reflexively performed for all total bilirubin values > 1.5X ULN.
b.
Glomerular Filtration Rate (GFR) will be estimated by the central laboratory using the Cockcroft-Gault method 
[Cockroft, 1976].
Fasting Lipid Panela
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
a.
For fasting lipids assessments, an overnight fast is preferred, however, a minimum of a 6 hour fast is acceptable 
Other tests 
Plasma HIV-1 RNA
CD4+ cell counts
Hepatitis B (HBsAg) and Hepatitis C (anti-HCV Ab)a
Pregnancy test for women of child bearing potential b
HLA-B*5701 screeninga
Urinalysis, urine albumin/creatinine ratio and urine protein/creatinine ratio 
Bone marker assessmentsc: bone specific alkaline phosphatase, Procollagen type 1 N-propeptide, 
Type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D
a.
Screening visit only 
b.
Urine pregnancy test on Day 1; serum pregnancy test at Screening and Weeks 4, 12, 24, 36 and 48 (and at 12 
weeks intervals thereafter if applicable).
c.
Blood sample for bone marker assessments: since the intention is to utilize these data for research purposes, the 
Sponsor will not report the results of these assessments to the investigator, except for 25 hydroxy-vitamin D.


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6.4.2.
Safety Endpoints

Incidence and severity of AEs and laboratory abnormalities; 

Absolute values and changes over time in laboratory parameters;

Proportion of subjects who discontinue treatment due to AEs;

Change from Baseline in fasting lipids and glucose;

Changes from Baseline in renal and bone markers.
6.4.3.
Toxicity Management
Adverse events that occur during the trial should be evaluated by the Investigator and
graded according to the Division of AIDS (DAIDS) toxicity scales (Appendix 2, Section 
11.2). Additional information regarding detecting, documenting and reporting AEs and 
SAEs are available in Section 6.4.5.
IP may be interrupted at the discretion of the Investigator and according to the severity of 
the AE. If one or more antiretroviral medication is held due to toxicity or adverse events, 
all antiretroviral medications should be held to reduce the risk of development of 
resistance taking into account both the length of the planned interruptions and the 
pharmacokinetic half-life of each antiretroviral of the regimen, in a way to minimize the 
risk of development of resistance.
No toxicity-related dose reductions of IP will be allowed. IP 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 IP or temporary interruption of one or more 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 general subject management and IP interruptions based on the severity of the AE; for 
specific toxicities, please refer to Section 6.4.4 “Specific Toxicities/Adverse Event 
Management”. All changes in the IP must be accurately recorded in the subject’s eCRF.
NOTE: In the event of a discontinuation of DTG/ABC/3TC FDC for any reason, 
reinitiation of this drug should be undertaken with caution. The investigator must obtain a
complete history of the events surrounding the discontinuation of DTG/ABC/3TC FDC,
evaluate for the possibility of a clinically suspected HSR, and initiate subject 
management as outlined in the DTG IB, regardless of a subject’s HLA-B*5701 status.
Grade 1 or Grade 2 Toxicity/Adverse Event
Subjects who develop a Grade 1 or Grade 2 AE or toxicity may continue IP at the
discretion of the Investigator. (NOTE: see Section 6.4.4 “Specific Toxicities/Adverse
Event Management” for exceptions to this guideline). Subjects who choose to withdraw
from study due to a Grade 1 or 2 AE should have study withdrawal and follow-up
evaluations completed.


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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 IP, dosing may continue after discussion with the medical monitor.
Subjects who develop a Grade 3 AE or toxicity, which the Investigator considers related
or possibly related to the IP, should have the IP withheld and be rechecked each week
until the AE returns to Grade 2. Once the AE is Grade ≤2, IP may be re-started.
Should the same Grade 3 AE recur within 28 days in the same subject, the IP should be
permanently discontinued and the subject withdrawn from study. Subjects experiencing
Grade 3 AEs requiring permanent discontinuation of IP should be followed weekly until
resolution of the AE and encouraged to have withdrawal study evaluations completed. A
Follow-Up visit should be performed 4 weeks after the last dose of IP.
Subjects with Grade 3 asymptomatic laboratory abnormalities should be investigated for
all potential non-drug related causes, and, following discussion with the medical monitor, 
may continue IP if the Investigator has compelling evidence that the toxicity is not related 
to IP. Exceptions are noted below for lipid abnormalities (Section 6.4.4.4).
Grade 4 Toxicity/Adverse Event
Subjects who develop a Grade 4 AE or toxicity should have IP permanently discontinued.
However, if the Investigator has compelling evidence that the AE is not causally related
to the IP, 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 IP 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 Grade 4 asymptomatic 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 IP. Exceptions are noted below for lipid abnormalities (Section 6.4.4.4).  A 
follow-up visit should be performed 4 weeks after the last dose of study medication if 
AEs or laboratory abnormalities are ongoing.
6.4.4.
Specific Toxicities/Adverse Event Management
General guidelines for the management of specific toxicities that are considered to be
related or possibly related to IP are provided below. 
Subjects who permanently discontinue IP for reasons of toxicity should be followed
weekly until resolution of the AE and encouraged to complete the withdrawal and
Follow-Up study evaluations as noted above.


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6.4.4.1.
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 IP and the follow-up period. 
IP will be stopped if any of the following liver chemistry criteria are met:

ALT ≥ 3xULN and bilirubin ≥2xULN (>35% direct bilirubin; bilirubin fractionation
required)

NOTE: serum bilirubin fractionation should be performed if testing is available.
If testing is unavailable, record presence of detectable urinary bilirubin on
dipstick, indicating direct bilirubin elevations and suggesting liver injury. If
testing is unavailable and a subject meets the criterion of total bilirubin 
≥2xULN, then the event meets liver stopping criteria;

ALT ≥8xULN;

ALT ≥3xULN (if baseline ALT is < ULN) with symptoms or worsening of acute
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant
pain or tenderness, fever, rash, or eosinophilia, OR;

ALT ≥3x baseline ALT with symptoms or worsening of acute hepatitis or 
hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, or eosinophilia;

ALT ≥5xULN and <8xULN that persists 2 weeks (with bilirubin <2xULN and no
signs or symptoms of acute hepatitis or hypersensitivity);

ALT ≥5xULN but <8xULN and cannot be monitored weekly for >2 weeks;
Subjects who develop ALT ≥5xULN should be followed weekly until resolution or
stabilization (ALT <5xULN on 2 consecutive evaluations).
When liver chemistry stopping criterion is met, do the following:

Immediately hold IP.  

Report the event to the medical monitor within 24 hours of learning its occurrence 
(see Table 5 and Table 6, Section 6.4.14);

Complete the liver event eCRF and SAE eCRF, where applicable, (see Section 
6.4.14);

Complete the liver imaging and/or liver biopsy eCRFs if these tests are performed;

Perform liver event follow up assessments (described below), and monitor the 
subject until liver chemistries resolve, stabilize, or return to baseline values as
described below;

Make every reasonable attempt to have subjects return to clinic within 24 hours for
repeat liver chemistries, liver event follow up assessments (see below), and close
monitoring;

A specialist or hepatology consultation is recommended;


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
Monitor subjects twice weekly until liver chemistries (ALT, aspartate 
aminotransferase (AST), alkaline phosphatase, bilirubin) resolve, stabilize or return 
to within baseline values;
Make every attempt to carry out the liver event follow up assessments described below:

Viral hepatitis serology including:

Hepatitis A IgM antibody;

HBsAg and Hepatitis B Core Antibody (IgM);

Hepatitis C RNA;

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

Serum acetaminophen test (APAP adduct test). The site must contact GSK when this 
test is required. Please refer to the SPM.

Hepatitis E IgM antibody;

Blood sample for pharmacokinetic (PK) analysis, obtained within 60 hours of last 
dose.  Record the date/time of the PK blood sample draw and the date/time of the last 
dose of IP prior to blood draw on the CRF.  If the date or time of the last dose is 
unclear, provide the subject’s best approximation.  If the date/time of the last dose 
cannot be approximated OR a PK sample cannot be collected in the time period 
indicated above, do not obtain a PK sample.  Instructions for sample handling and 
shipping are in the SPM.

Serum CPK and lactate dehydrogenase (LDH);

Fractionate bilirubin, if total bilirubin is greater than 1.5xULN;

Obtain complete blood count with differential to assess eosinophilia;

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney
microsomal antibodies;

Liver imaging (ultrasound, magnetic resonance, or computerized tomography) to
evaluate liver disease;

Record the appearance or worsening of clinical symptoms of hepatitis, or
hypersensitivity, fatigue, decreased appetite, nausea, vomiting, abdominal pain,
jaundice, fever, or rash as relevant on the AE report form;

Record use of concomitant medications, acetaminophen, herbal remedies, other over
the counter medications, or putative hepatotoxins, on the concomitant medications
report form. Record alcohol use on the liver event alcohol intake case report form.


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6.4.4.2.
Restarting Investigational Product
Drug Restart/Rechallenge Following Liver Events that are Possibly Related to IP
Approval by the ViiV Safety and Labeling Committee (VSLC) for drug restart can be 
considered where:

The subject is receiving compelling benefit, benefit of drug restart exceeds risk, and 
no effective alternative therapy is available. Ethics Committee or Institutional 
Review Board approval of drug restart/rechallenge must be obtained, as required.

If the restart/rechallenge is approved by the VSLC in writing, the subject must be 
provided with a clear description of the possible benefits and risks of drug 
administration, including the possibility of recurrent, more severe liver injury or 
death.

The subject must also provide signed informed consent specifically for the IP 
restart/rechallenge. Documentation of informed consent must be recorded in the 
study chart.

Study drug must be administered at the dose specified by the VSLC.

Subjects approved by the VSLC for rechallenge of IP must return to the clinic twice 
a week for liver chemistry tests for one month or for as long as clinically indicated
and then laboratory monitoring may resume as per protocol.
Refer to Appendix 4, Section 11.4 for further details. 
Drug Restart Following Transient Resolving Liver Events Not Related to IP 
Approval by the VSLC for drug restart can be considered where:

Liver chemistries have a clear underlying cause (e.g., biliary obstruction, 
hypotension and liver chemistries have improved to normal or are within 
1.5 x baseline and ALT <3xULN). Ethics Committee or Institutional Review Board 
approval of drug restart/rechallenge must be obtained, as required.

If restart of drug is approved by the VSLC in writing, the subject must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.

The subject must also provide signed informed consent specifically for the restart.  
Documentation of informed consent must be recorded in the study chart.

Study drug must be administered at the dose specified by the VSLC.
Subjects approved by the VSLC for restarting IP must 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 as per protocol.  If protocol defined stopping criteria 
for liver chemistry elevations are met, study drug must be stopped.
Refer to Appendix 4, Section 11.4 for further details. 


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6.4.4.3.
ATV related hyperbilirubinemia
For isolated Grade 3 unconjugated hyperbilirubinemia attributed to ATV, ATV should 
be continued unless associated with jaundice or scleral icterus that presents an intolerable 
cosmetic concern to the subject.  For isolated elevations Grade 3 that cannot be 
attributed to ATV or to a cause that is not study drug-related, all study medications 
should be held pending evaluation of etiology.  
In the event that an elevation in total bilirubin to 2x ULN (>35% direct bilirubin, 
bilirubin fractionation required) is accompanied by an increase in ALT ≥3x ULN, then 
the instructions set out in Section 6.4.4.1 must be followed.
6.4.4.4.
Hypertriglyceridemia/Hypercholesterolemia
Samples for lipid measurements must be obtained in a fasted state according to the Time 
and Events table (Section 6.1). Subjects who experience asymptomatic triglyceride or 
cholesterol elevations may continue to receive IP.
6.4.4.5.
CPK Elevation
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2-4
weeks to ensure the result is transient or due to exercise and will not require a change in
study treatment. A history regarding use of drugs known to cause increase of CPK (such
as statins) physical activity or exercise preceding the CPK evaluation should be obtained.
Grade 4 elevations in CPK should have a repeat assessment after the subject has
abstained from exercise for >24 hours. For persistent Grade 4 CPK elevations that are
considered possibly or probably related to the IP, IP should be discontinued and the
subject withdrawn from the study.
6.4.4.6.
Decline in Renal Function
Subjects who experience an increase in creatinine from Baseline of 45 Mol/L (or
0.5 mg/dL) without associated evidence for proteinuria should return for a confirmatory 
assessment within 2 to 4 weeks.  A urinalysis and urine albumin/creatinine ratio should 
be done at this confirmatory visit.  If the creatinine increase is confirmed, the investigator 
should contact the study medical monitor to discuss additional follow-up and medical 
management.
The following criteria are defined based on Cockcroft-Gault estimates of glomerular 
filtration rate. The criteria are based on recommendations for changes in dosing
administration for both DTG/ABC/3TC FDC and TDF/FTC FDC. The DTG IB and 
current local prescribing information for TDF/FTC FDC should be consulted for 
additional details on dosing in renally impaired subjects.
Subjects who have a decline in CrCL of >50% must return for a confirmatory assessment 
as soon as possible. A urinalysis and urine albumin/creatinine ratio should be done at this 
confirmatory visit. If the estimated CrCL has declined by >50% (confirmed), then IP 
should be withheld and the investigator should contact the study medical monitor to 


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discuss the rationale for restarting study drugs (if appropriate).  Consideration for 
confounding factors (e.g., other medications, dehydration, concurrent conditions) should 
be taken into account, and a nephrology consult may be obtained.  If IP is reinitiated, it 
should have been withheld for no more than 4 weeks.  If IP is not reinitiated the subject 
must be withdrawn.
Proximal Renal Tubule Dysfunction (PRTD) is defined as:

Confirmed rise in serum creatinine of ≥0.5mg/dL from Baseline AND serum
phosphate <2.0mg/dL;

Either of the above accompanied by any two of the following:

Glycosuria (≥250mg/dL) in a non-diabetic;

Low serum potassium (<3mEq/L);

Low serum bicarbonate (<19mEq/L).
Subjects meeting criteria for PRTD must return for a confirmatory assessment within 2
weeks. A urinalysis should be done at the time of the confirmatory assessment. If PRTD
is confirmed subjects should have IP withheld and the investigator should contact the
study medical monitor to discuss the rationale for restarting study drugs (if appropriate). 
If reinitiation of IP is planned, IP should be withheld for no more than 4 weeks.
6.4.4.7.
Proteinuria
Subjects with an abnormal urine albumin/creatinine ratio (>0.3mg/mg, >300mg/g or 
>34mg/mmol) that represents a change from Baseline and no associated increase in 
creatinine, should have a repeat spot urine albumin/creatinine ratio performed within 2-4 
weeks. If confirmed, then consideration should be made for additional evaluation after 
consultation with the study medical monitor. Additional evaluation may include a 24 hr 
urine protein and creatinine measurement and nephrology referral.
Subjects with an abnormal urine albumin/creatinine ratio (>0.3mg/mg, 300 mg/g 
or>34mg/mmol and representing a change from Baseline) and a serum creatinine increase 
>45 Mol/L (or 0.5 mg/dL) should have confirmation of both results within 2 weeks.  If 
confirmed, the study medical monitor should be immediately contacted.  Agreement on 
further management should be agreed between the investigator and medical monitor.
6.4.4.8.
Allergic Reaction
Subjects may continue IP 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 IP should permanently discontinue the IP regimen and the subject should be
withdrawn from the study. Subjects should be treated as clinically appropriate and
followed until resolution of the AE.


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Subjects receiving DTG/ABC/3TC FDC should be managed in terms of a clinically 
suspected ABC hypersensitivity, as described below.
6.4.4.9.
Abacavir Hypersensitivity Reaction (ABC HSR)
The most significant toxicity associated with ABC is the well-characterized drug-related
HSR. A detailed clinical description of this reaction (including the type and severity of 
events that can occur on re-challenge or reintroduction following ABC interruption for 
non-HSR reasons) and guidance regarding its management are included in the DTG IB.  
Investigators must familiarize themselves with this information on ABC HSR in the IB 
for each of these products prior to initiating subjects on ABC therapy.
Studies have shown that carriage of the HLA-B*5701 allele is associated with a
significantly increased risk of a HSR to ABC. 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 HSR from 7.8% (66 of 847) to 3.4% (27 of 803)
(p<0.0001). 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 HSR, respectively.
In any subject treated with ABC, the clinical diagnosis of suspected HSR (as
detailed in the IB) must remain the basis of clinical decision making. Regardless of 
HLA-B*5701 status, it is important to permanently discontinue ABC and not re-
challenge with ABC (i.e., ZIAGEN™, EPZICOM, KIVEXA, TRIZIVIR™ or 
DTG/ABC/3TC FDC) if a HSR cannot be ruled out on clinical grounds, due to the 
potential for a severe or even fatal reaction.
Essential Patient Information 
With reference to the IB and the ‘Subject Information and Consent Form’, Investigators 
must ensure that subjects are fully informed regarding the following information on the 
HSR prior to commencing ABC therapy:

Subjects must be made aware of the possibility of a HSR to abacavir that may result 
in a life-threatening reaction or death and that the risk of a HSR is increased in 
individuals who are HLA-B*5701 positive.

Subjects must also be informed that HLA-B*5701 negative individuals can also
experience abacavir HSR. Therefore, ANY subject who develops signs or symptoms 
consistent with a possible HSR to abacavir MUST CONTACT their doctor 
IMMEDIATELY.

Subjects who are hypersensitive to abacavir should be reminded that they must never
take any abacavir containing medicinal products (e.g. DTG/ABC/3TC, ZIAGEN, 
EPZICOM, KIVEXA or TRIZIVIR) again, regardless of their HLA-B*5701 status.

In order to avoid restarting abacavir, subjects who have experienced a HSR should 
be asked to return any remaining DTG/ABC/3TC FDC tablets to the Investigator or 
site staff.


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
Subjects who have stopped abacavir for any reason, and particularly due to possible
adverse reactions or illness, must be advised to contact their doctor before restarting
DTG/ABC/3TC.

Each subject should be reminded to read the Abacavir Hypersensitivity Warning 
Card accompanying their study medication and of the importance of keeping it with 
them at all times.
Reporting of Hypersensitivity Reactions
If a clinically suspected case of HSR to ABC meets one of the International Conference 
on Harmonization (ICH)-E2A definitions of seriousness listed in Section 6.4.5.2, then, in 
addition to reporting the case as an SAE, the ABC HSR CRF should also be completed 
within one week of the onset of the hypersensitivity reaction.
6.4.4.10.
Skin reactions without other symptoms that are typical of ABC HSR
Including serious skin reactions such as SJS, TEN, Erythema Multiforme or rash 
with significant liver dysfunction 
Subjects should be instructed to contact the Investigator as soon as possible if they 
develop a rash while on study.
Subjects who develop rash of any grade should be evaluated for the possibility of an 
ABC HSR or a serious skin reaction such as SJS, TEN or Erythema Multiforme. SJS, 
TEN and Erythema Multiforme have been reported very rarely in patients taking ABC-
containing products.  These patients generally do not have the cluster of additional 
symptoms (e.g., gastrointestinal and respiratory) that characterize the ABC HSR, but they 
do have features typical of these serious skin reactions.
If a serious skin reaction develops, ABC (and / or all other concurrent medication(s) 
suspected in the Investigators causality assessment) should be discontinued, and the 
subject should not be re-challenged with any ABC-containing medicinal product (i.e., 
DTG/ABC/3TC, ZIAGEN, TRIZIVIR, EPZICOM or KIVEXA).
As many products other than abacavir also cause rash and/or serious skin reactions, all 
other medicinal products that the subject is receiving should also be reviewed and 
discontinued as appropriate.
Severe, potentially life-threatening, and fatal skin reactions, including cases of SJS and 
TEN are listed events in the Local Country Prescribing Information for the first marketed 
integrase inhibitor, RAL [Isentress US Package Insert, April 2013; Isentress, EU 
Summary of Product Characteristics, March 2013], and hypersensitivity reactions have 
been reported with integrase inhibitors, including dolutegravir, and were characterized by 
rash, constitutional findings, and sometimes, organ dysfunction, including liver injury. 
For additional information on rash associated with dolutegravir, please see the current 
version of the DTG IB [GSK Document Number RM2007/00683/11, GSK Document 
Number 2017N352880_00, GSK Document Number 2017N352880_01].


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SJS, erythema multiforme, toxic skin eruptions and drug rash with eosinophilia and 
systemic symptoms (DRESS) syndrome have also been reported in patients receiving 
ATV [Reyataz US Package Insert, April 2013; Reyataz EU Summary of Product 
Characteristics, September 2012].
The following guidance is provided for clinical management of subjects who experience 
rash alone in the absence of accompanying diagnosis of ABC HSR, systemic or allergic 
symptoms or signs of mucosal or target lesions.
Subjects with an isolated Grade 1 rash may continue IP at the Investigator’s discretion. 
The subject should be advised to contact the Investigator immediately if there is any 
worsening of the rash, if any systemic signs or symptoms worsen, or if mucosal 
involvement develops.
Subjects may continue IP for an isolated Grade 2 rash. However, IP (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 (see Section 6.4.4.1). The subject should be advised to contact the physician 
immediately if rash fails to resolve (after more than two weeks), if there is any worsening 
of the rash, if any systemic signs or allergic symptoms develop, or if mucosal 
involvement develops.
Subjects should permanently discontinue IP (and all other concurrent medication(s) 
suspected in the Investigators causality assessment) for an isolated Grade 3 or 4 rash, and 
the subject should be withdrawn from the study. Subjects should be treated as clinically
appropriate and followed until resolution of the AE.
The rash and any associated symptoms should be reported as adverse events (see 
Section 6.4.5) and appropriate toxicity ratings should be used to grade the events (see 
Appendix 2, Section 11.2).
If the etiology of the rash can be definitely diagnosed as being unrelated to IP and due to 
a specific medical event or a concomitant non-study medication, routine management 
should be performed and documentation of the diagnosis provided.
6.4.5.
Adverse Events
The investigator or site staff will be responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.
6.4.5.1.
Definition of an AE
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 


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associated with the use of a medicinal product.  For marketed medicinal products, this 
also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Events meeting the definition of an AE include:

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.
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. However, the signs and symptoms and/or clinical sequelae 
resulting from lack of efficacy will be reported if they fulfil the definition of an AE or 
SAE.  
Events that do not meet the definition of an AE include:

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
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

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
6.4.5.2.
Definition of an SAE
A serious adverse event is any untoward medical occurrence that, at any dose:
Results in death
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.
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 


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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.
Results in disability/incapacity, or
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.
Is a congenital anomaly/birth defect
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.
All events of possible drug-induced liver injury with hyperbilirubinaemia defined as ALT 
3xULN and bilirubin 2xULN (>35% direct) (or ALT 3xULN and INR>1.5, if INR 
measured) termed ‘Hy’s Law’ events (INR measurement is not required and the threshold 
value stated will not apply to patients receiving anticoagulants).
NOTE: bilirubin fractionation is performed if testing is available. If testing is 
unavailable, record presence of detectable urinary bilirubin on dipstick indicating 
direct bilirubin elevations and suggesting liver injury. If testing is unavailable and a 
subject meets the criterion of total bilirubin 2xULN, then the event is still reported 
as an SAE. If INR is obtained, include values on the SAE form. INR elevations >1.5 
suggest severe liver injury.  
6.4.6.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, and felt to be clinically significant in the 
medical and scientific judgment of the investigator are to be recorded as AEs or SAEs. 
However, any clinically significant safety assessments that are associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for 
the subject’s condition, are not to be reported as AEs or SAEs.


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It is important to note that grading for laboratory abnormalities (See Section 11.2) is an 
objective assessment conducted at the central laboratory and does not translate directly 
into similarly graded AEs.
6.4.7.
Cardiovascular Events
Investigators will be required to fill out event specific data collection tools for the 
following AEs and SAEs:  

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thrombosis

Deep Venous Thrombosis

Revascularisation
This information should be recorded within one week of when the AE/SAE(s) are first 
reported.
6.4.8.
Death Events
In addition, all deaths will require a specific death data collection tool to be completed.  
The death data collection tool includes questions regarding cardiovascular (including 
sudden cardiac death) and noncardiovascular death.
This information should be recorded within one week of when the death is first reported.
6.4.9.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs
The events or outcomes listed in the CDC Classification System for HIV-1 Infections 
(Appendix 1, Section 11.1 [CDC, 1993]) will be recorded on the HIV Associated 
Conditions CRF page if they occur.  However, these individual events or outcomes, as 
well as any sign, symptom, diagnosis, illness, and/or clinical laboratory abnormality that 
can be linked to any of these events or outcomes are not reported to GSK as AEs and 
SAEs even though such event or outcome may meet the definition of an AE or SAE, 
unless the following conditions apply:

the Investigator determines that the event or outcome qualifies as an SAE under part 
‘f’ of the SAE definition (see Section 6.4.5.2), or


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
the event or outcome is in the Investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual subject, or

death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly.
Lymphomas and invasive cervical carcinomas are excluded from this exemption; they 
must be reported as SAEs even if they are considered to be HIV related.
6.4.10.
Suicidality Monitoring
Patients with HIV infection may occasionally present with symptoms of depression 
and/or suicidality (suicidal ideation or behavior). Therefore, it is appropriate to monitor 
subjects for suicidality before and during treatment. It is recommended that the 
Investigator consider mental health consultation or referral for subjects who experience 
signs of suicidal ideation or behavior.
Treatment emergent assessment of suicidality will be monitored during this study using 
the Columbia Suicide Severity Rating Scale (C-SSRS). The definitions of behavioral 
suicidal events used in this scale are based on those used in the Columbia Suicide History 
Form [Oquendo, 2003]. Questions are asked on suicidal behavior, suicidal ideation and 
intensity of ideation. Day 1 (Baseline) visit questions will be in relation to lifetime 
experiences and current experiences (within the past 2 months) and all subsequent 
questioning in relation to the last assessment. The C-SSRS is to be administered using an 
interactive voice response system at the time-points specified in Section 6.1.
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the AE (Non-serious or SAE) eCRF form 
on any subject that experiences a possible suicidality-related adverse event while 
participating in this study. This may include, but is not limited to, an event that involves 
suicidal ideation, a preparatory act toward imminent suicidal behavior, a suicide attempt, 
or a completed suicide.  The investigator will exercise his or her medical and scientific 
judgment in deciding whether an event is possibly suicide-related.  PSRAE forms should 
be completed and reported to GSK within one week of the investigator diagnosing a 
possible suicidality-related adverse event.
6.4.11.
Pregnancy
6.4.11.1.
Pregnancy Testing
Women of childbearing potential must have a negative pregnancy test at Screening and 
Day 1 to be eligible for administration of IP.  Pregnancy testing will also be conducted as 
per the Time and Events Table (See Section 6.1) and at anytime during the trial when 
pregnancy is suspected.
Additionally, a pregnancy test should also be performed prior to IP re-administration, 
when administration is disrupted for more than 7 days (e.g. temporary interruption of IP).


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6.4.11.2.
Action to be Taken if Pregnancy Occurs
Any female who becomes pregnant (intrauterine) while participating in this study must be 
withdrawn from the study and discontinue IP.
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  To ensure subject safety, each pregnancy must be reported to GSK 
within 2 weeks of learning of its occurrence.  The pregnancy must be followed up to 
determine outcome (including premature termination) and status of mother and child.  
Pregnancy complications and elective terminations for medical reasons must be reported 
as an AE or SAE.  Spontaneous abortions must be reported as an SAE.
Any SAE occurring in association with a pregnancy, brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK.
GSK’s central safety department will also forward this information to the Antiretroviral 
Pregnancy Registry. The international registry is jointly sponsored by manufacturers or 
licensees of antiretroviral products. Additional information and a list of participating 
manufacturers/licensees are available from http://apregistry.com/index.htm.
6.4.11.3.
Time Period for Collecting Pregnancy Information
Information on the occurrence of pregnancies in female subjects will be collected over 
the period starting at Screening and ending at the final on-study or Follow-up visit. Only 
those pregnancies that occur following the first dose of IP will be reported to GSK. 
Follow-up information will only be collected for pregnancies occurring from Day 1 to the 
final on-study or Follow-up visit.
6.4.12.
Time Period and Frequency of Detecting AEs and SAEs
The investigator or site staff is responsible for detecting, documenting and reporting
events that meet the definition of an AE or SAE.
AEs will be collected from the start of study treatment and until the follow up contact.  
SAEs will be collected over the same time period as stated above for AEs. However, any 
SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant 
medication, will be recorded from the time a subject consents to participate in the study 
up to and including any follow up contact. All SAEs will be reported to GSK within 24 
hours, as indicated in Section 6.4.14. 
6.4.13.
Method of Detecting AEs and SAEs
Care must be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence. Appropriate questions include:


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“How are you feeling?” 
“Have you had any (other) medical problems since your last visit/contact?”
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact?”
6.4.14.
Prompt Reporting of Serious Adverse Events and Other Events 
to GSK
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to GSK as described in Table 5 and Table 6 once 
the investigator determines that the event meets the protocol definition for that event.
Table 5
Events and Reporting Time Periods for SAEs
Initial Reports
Follow-up Information on a 
Previous Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs 
24 hours 
SAE data collection 
tool
24 hours
Updated SAE data 
collection tool 
ALT≥3xULN plus 
Bilirubin≥2xULN (35% 
direct)
24 hours1
SAE data collection 
tool Liver Event 
CRF and liver 
imaging and/or 
biopsy CRFs if 
applicable 
24 hours 
Updated SAE data 
collection tool 
Updated Liver Event 
CRF2


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Table 6
Other Events Requiring Prompt Reporting
Initial Reports
Follow-up Information on a 
Previous Report
Type of Event
Time Frame
Documents
Time Frame
Documents
Pregnancy 
2 Weeks 
Pregnancy 
Notification Form 
2 Weeks 
Pregnancy Follow 
up Form 
Suspected ABC HSR 
1 Week
ABC HSR CRF3
1 Week
Updated ABC HSR 
CRF3
ALT≥5xULN that 
persists ≥2 weeks 
24 hours1
Liver Event CRF2
24 hours 
Updated Liver Event 
CRF2
ALT ≥8xULN 
24 hours1
Liver Event CRF2
24 hours 
Updated Liver Event 
CRF2
ALT ≥3xULN or ALT ≥3 
fold increase from 
baseline value with 
24 hours1
Liver Event CRF2
24 hours 
Updated Liver Event 
CRF2
appearance or 
worsening of symptoms 
of hepatitis or 
hypersensitivity
1.
GSK must be contacted at onset of liver chemistry elevations to discuss subject safety
2.
Liver Event Documents (i.e., “Liver Event CRF” and “Liver Imaging CRF” and/or “Liver Biopsy CRF”, as 
applicable) should be completed as soon as possible.
3.
ABC HSR CRF required only if event meets one of the ICH-E2A definitions of seriousness’.
The method of recording, evaluating and follow-up of AEs and SAEs plus procedures for 
completing and transmitting SAE reports to GSK are provided in the SPM.  Procedures 
for post-study AEs/SAEs are provided in the SPM.
Procedures for documenting, transmitting and follow-up of medical device incidents 
along with the regulatory reporting requirements for medical devices are provided in the 
SPM.
6.4.14.1.
Regulatory Reporting Requirements for SAEs
Prompt notification of SAEs by the investigator to GSK is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/ IEC and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.


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An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
6.4.15.
Other Safety Outcomes
Laboratory Assessments
All protocol required laboratory assessments, as defined in [Table 4], must be performed 
by the central laboratory, Quest Diagnostics. Laboratory assessments must be conducted 
in accordance with the Central Laboratory Manual and Protocol Time and Events Table.
Laboratory requisition forms must be completed and samples must be clearly labeled 
with the subject number, protocol number, site/centre number, and visit date. Details for 
the preparation and shipment of samples will be provided by Quest Diagnostics.
Reference ranges for all safety parameters will be provided to the site by Quest 
Diagnostics.
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in patient management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the subject’s CRF. Refer to the SPM for 
appropriate processing and handling of samples to avoid duplicate and/or additional 
blood draws.
6.5.
Health Outcomes
Health outcomes assessments will be conducted in all countries according the schedule in 
the Time and Events Table (Section 6.1).  Assessments are recommended to be 
administered at the beginning of the visit.
Health Related Quality of Life (HRQoL) will be assessed by the SF-12 (12-Item Short 
Form Health Survey) which was derived from the 36-Item Short Form Health Survey 
(SF-36) and has been shown to provide adequate mental component summary (MCS) and 
well as physical component summary (PCS) scores [Ware, 1996]. The SF-12 has been 
studied in the HIV population and can discriminate between patients by HIV disease 
severity as measured by CD4+ cell count and HIV-1 viral load.  The SF-12 will be 
administered as a paper questionnaire.
HIVTSQ: The HIV treatment satisfaction questionnaire (status version) [Woodcock , 
2001; Woodcock, 2006] is a 10-item self-reported scale that measures overall satisfaction 
with treatment and by specific domains e.g. convenience, flexibility. The HIVTSQ will 
be administered as a paper questionnaire.  
6.5.1.
Health Outcomes Endpoints

Change from Baseline in health related quality of life using SF-12 at Week 48.


2 0 1 3 N 1 6 1 6 4 9 _ 0 3
C O N FI D E N TI A L
I NG 1 1 7 1 7 2
6 9

Treat me nt satisfacti o n f or s u bjects treate d wit h D T G/ A B C/ 3 T C F D C o nce dail y  a n d
t h ose treate d wit h A T V + R T V +T D F/ F T C F D C o nce dail y at wee ks 4, 1 2, 2 4, a n d 4 8 
( or wit h dra wal fr o m t he st u d y).
6. 6.
Vir al G e n ot y pi n g a n d P h e n ot y pi n g
W h ole ve n o us bl o o d sa m ples will be o btai ne d fr o m eac h s u bject t o pr o vi de ‘ plas ma f or
st ora ge sa m ples’ acc or di n g to t he Ti me a n d E ve nts Sc he d ule i n Secti o n 6. 1 (f or p ote ntial 
viral ge n ot y pic a n d p he n ot y pic a nal ys es (‘ Plas ma f or st ora ge’ sa m ples). 
Details c o ncer ni n g t he ha n dli n g, la beli n g a n d s hi p pi n g of t hese sa m ples will be s u p plie d
se paratel y. Ge n oty pic a n d p he n ot y pic a nal ys es ma y be carrie d o ut b y M o n o gra m
Bi oscie nces usi n g, b ut n ot li mite d t o, t heir Sta n dar d P he n ose nse a n d Ge n o S ure testi n g
met h o ds f or pr otease ( P R O) a n d re verse tra nscri ptase ( R T) a n d I nte grase assa ys.
F or Scree ni n g vir ol o gic e val uati o ns, o nl y  viral ge n ot ype will be a nal yz e d a n d t his will be
perf or me d t hr o u g h Q uest Dia g n ostics.
6. 6. 1.
Vir ol o g y  E n d p oi nt s

I nci de nce of treat me nt -e mer ge nt ge n ot y pic a n d p he n ot y pic resista nce i n s u bjects
w h o meet c o nfir me d vir ol o gic w it h dra wal criteria.
6. 6. 2.
HI V- 1 P ol y m er a s e Vir al G e n ot y pi n g a n d P h e n ot y pi n g
At Scree ni n g, sa m ples will be c ollecte d f or HI V -1 p ol y merase ( p ol) ge n ot y pe usi n g a 
Q uest Dia g n ostics ge n ot y pe assa y  a n d res ults will be pr o vi de d t o t he I n vesti gat or t o assist 
i n t he det er mi nati o n of s u bject eli gi bilit y ( Secti o n 4. 3 ).
S u bjects meeti n g ‘c o nfir me d vir ol o gic wit h dra wal criteri o n’ will ha ve plas ma sa m ples 
teste d f or HI V - 1 P R O a n d R T ge n ot y pe a n d p he n ot y pe a n d HI V -1 i nte grase ge n ot y pe 
a n d p he n ot y pe fr o m b ot h Baseli ne sa m ples a n d fr o m sa m ples c ollecte d at t he ti me of 
meeti n g ‘s us pecte d vir ol o gic wit h dra wal criteri o n’ (a d diti o nal s u bse q ue nt sa m ples ma y  
be a nal yz e d); t hese res ults will be re p orte d t o t he I n vesti gat or as s o o n as a vaila ble t o 
pr o vi de g ui da nce f or electi o n of a n alter nati ve re gi me n.
C CI


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6.7.
Pharmacogenetic Research
Information regarding PGx research is included in Appendix 3 (Section 11.3).  
The IEC/IRB and, where required, the applicable regulatory agency must approve the 
PGx assessments before these can be conducted at the site. The approval(s) must be in 
writing and will clearly specify approval of the PGx assessments (i.e., approval of 
Appendix 3, Section 11.3).  In some cases, approval of the PGx assessments can occur 
after approval is obtained for the rest of the study. If so, then the written approval will 
clearly indicate approval of the PGx assessments is being deferred and the study, except 
for PGx assessments, can be initiated. When PGx assessments will not be approved, then 
the approval for the rest of the study will clearly indicate this and therefore, PGx 
assessments will not be conducted.
7.
DATA MANAGEMENT
For this study, subject data will be entered into GSK defined eCRFs, transmitted 
electronically to GSK or designee and combined with data provided from other sources in 
a validated data system.  
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
errors and inconsistencies in the data.  Adverse events and concomitant medications 
terms will be coded using MedDRA and an internal validated medication dictionary, 
GSKDrug.  eCRFs (including queries and audit trails) will be retained by GSK, and 
copies will be sent to the investigator to maintain as the investigator copy.  In all cases, 
subject initials will not be collected or transmitted to GSK according to GSK policy.
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
8.1.
Hypotheses
This study is designed to show that the antiviral effect of the DTG/ABC/3TC FDC 
administered once daily is non-inferior to once daily ATV+RTV+TDF/FTC FDC. 
Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence 
interval for the difference in response rates between the two treatment arms is greater 
than -12%. If rd is the response rate on DTG/ABC/3TC FDC and ra is the response rate on 
ATV+RTV+TDF/FTC FDC then the hypotheses can be written as follows:
H0: rd – ra ≤ -12% 
H1: rd – ra > -12%.


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8.2.
Study Design Considerations
8.2.1.
Sample Size Assumptions
Rationale for non-inferiority margin
A non-inferiority margin is set as 12% in this study. The rationale is shown in Table 7. 
The endpoint for the primary comparison is response rate, i.e. the proportion of subjects 
with plasma HIV-1 RNA below 50 c/mL at Week 48. Table 7 shows the response rates 
from studies of dual-NRTI therapy and dual-NRTI + third agent therapy. Though time 
points are different among the studies, the differences of response rates between dual-
NRTI therapy and dual-NRTI + third agent are similar. These differences in response 
rates range from 34% to 49% and all of the lower bounds of 95% confidence interval are 
no less than 0%, which shows that the additional effect of third agent therapy in each 
study is statistically significant. Moreover, the pooled difference (the 95% confidence 
interval) of these response rates is 39% (33%, 45%). A non-inferiority margin of 12% is 
small enough compared to the additional effect of third agent therapy, because the non-
inferiority margin is much less than the half of the lower bound of 95% confidence 
interval for the pooled difference.
Also the non-inferiority margin of 12% is in the mid-range of the margins described in a 
review of non-inferiority trials in HIV conducted between 2000 and 2007, where the 
margins vary between 10% and 15% [Hill, 2008]. This suggests further that a non-
inferiority margin of 12% is reasonable.
Table 7
The proportion of subjects with plasma HIV-1 RNA below 50 c/ml of 
dual-NRTI therapy and dual NRTI + third agent therapy
Study 
Number
N
Endpoint
Timepoint
Dual-NRTI
Therapy
Dual-NRTI
Therapy + Third Agent
Differencea
(95% CI)
Response Rate
Response Rate
PROAB3001
232
<50 c/ml
Week 48
ZDV+3TC
1%(1/116)
ZDV+3TC+APV
34%(40/116)
34%
(20.7%,
45.7%)
CNAAB3003
173
<50 c/ml
Week 48
ZDV+3TC
3%(3/86)
ZDV+3TC+ABC
44%(38/87)
40%
(26.2%,
53.3%)
AVANTI-2
103
<50 c/ml
Week 52
ZDV+3TC(n=51)
6%
ZDV+3TC+IDV(n=52)
48%
42%
(24.2%,
58.8%)
AVANTI-3
105
<50 c/ml
Week 28
ZDV+3TC(n=52)
10%
ZDV+3TC+NFV(n=53)
58%
49%
(31.7%,
64.7%)
a. Defined as the difference of response rate calculated by (dual-NRTI + third agent) - (dual-NRTI therapy)
Response Rate assumptions
In previous DTG and ATV/RTV studies, response rates in women have consistently been 
lower than those seen in men. Results of DTG studies can be found in the most current 
version of the IB.


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In the SINGLE study (ING114467) comparing DTG+ABC/3TC once daily to Atripla 
once daily in treatment naive subjects, the overall response rate <50 c/ml (ITT-E, 
Snapshot) at Week 48 for the DTG arm was 88% (364/414) with a 85% (57/67) response 
rate in women compared to 88% (307/347) in men. In the SPRING-2 study (ING113086) 
comparing DTG once daily to RAL BID both in combination with a fixed dose dual 
NRTI treatment, the overall response rate <50 c/ml (ITT-E, Snapshot) at Week 48 for the 
DTG arm was 88% (361/411) with a 84% (53/63) response rate in women compared to 
89% (308/348) in men. 
In the CASTLE study [Molina, 2008] comparing ATV+RTV+FTC once daily to 
LPV/RTV +FTC once daily in treatment naive subjects, the overall response rate <50c/ml 
(ITT, non completers = failure) was 78% (343/440) at Week 48 in the ATV/RTV arm. 
Gender differences in response rates were published for the Week 96 analysis [Squires, 
2011] where the overall response rate <50 c/ml (ITT, non completers=failure) was 74% 
(327/440) with a 67% (93/138) response rate in women compared to 77% (234/302) in 
men. 
A recent study [DeJesus, 2012] comparing ATV+RTV+FTC/TDF to Stribild 
(ELV/COBI/TDF/FTC) in HIV-1 infected ART naive subjects reported an overall 
response rate of 87% (308/355) <50 c/ml (ITT, Snapshot). The corresponding response 
rate in women was 82% (32/39) compared to 87% (276/316) in men. However, with so
few subjects included in the study, the estimate of the response rate in women is not 
robust. 
The response rates for the four studies are shown together in Table 8.
Table 8
The proportion of subjects with plasma HIV-1 RNA below 50 c/ml
DTG Response Rates
ATV/RTV Response Rates
SINGLEa
Week 48
SPRING-2a
Week 48
CASTLEb
Week 48
CASTLEb
Week 96
DeJesusa
Week 48
All
88%
80%
78%
74%
87%
Men
88%
89%
-
77%
87%
Women
85%
84%
-
67%
82%
a – ITT-E Snapshot 
b – ITT, non completers=failure
The discontinuation rates observed in women across HIV studies are higher than those 
observed in men and vary between studies. With a Snapshot analysis, subjects who 
discontinue from the study are considered to be non-responders at subsequent visits and 
as such can have a substantial impact on the response rates observed. 
The overall discontinuation rates for women compared with men were 23% (30/130) 
versus 15% (105/703), and 18% (22/119) versus 11% (81/703) in the Week 48 analyses 
from SINGLE and SPRING-2 studies, respectively. In the Week 48 analysis of the 
CASTLE study, the overall discontinuation rate was 12% (53/440). The gender 


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differences published for the Week 96 analysis show a higher rate in women of 22% 
(31/138) compared to 15% (45/302) in men. One of the few studies specifically designed 
to look at the outcomes by gender, the GRACE study [Currier, 2010] using 
darunavir+RTV, reported a discontinuation rate of 33% (94/287) in women compared to 
23% (33/142) in men. However, it should be noted that this study was in treatment-
experienced patients. The number of female subjects in these studies, with the exception 
of the GRACE study, was relatively small and as such the estimates of response rates will 
not be as robust as those overall or for men. There has also been a wide range of 
discontinuation rates observed with a clear signal that the rates in women are higher than 
in men. It may be possible to reduce the number of avoidable discontinuations through 
careful and well thought out study design and management but it is likely that a higher 
rate of discontinuation will be seen in this study than in previous mixed gender DTG 
studies.
The discontinuation rates for these four studies are shown together in Table 9.
Table 9
Premature Discontinuation Rates
DTG Discontinuation Rates
ATV/RTV Discontinuation Rates
SINGLE
Week 48
SPRING-2
Week 48
CASTLE 
Week 48
CASTLE
Week 96
GRACE
Week 48
All
16%
13%
12%
17%
30%
Men
15%
11%
-
15%
23%
Women
23%
18%
-
22%
33%
The primary efficacy endpoint will be the proportion of subjects achieving <50 c/ml in 
HIV-1 RNA at Week 48 using a Snapshot analysis and an ITT-E population. Therefore, 
assuming an 80% response rate in both arms with a 12 % non-inferiority margin and a 
2.5% level of significance, a sample size of 237 subjects per arm would provide 90% 
power.
8.2.2.
Sample Size Sensitivity
Table 10 shows the sensitivity of the sample size and the power to the assumptions used 
in its calculation. The table shows that the planned sample size still provides at least 85% 
power if the assumptions of 80% response rate per arm vary as indicated.


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Table 10
Calculation of sample size and power based on assumptions for 
response rates
Week 48 Response Rate 
DTG vs. ATV
Sample Size per arm
(based on 90% power)
Power
(based on 237 subjects per 
arm)
85% vs. 85% 
194
95%
80% vs. 75% 
129
99%
80% vs. 80% 
237
90%
75% vs. 70% 
146
99%
75% vs. 75% 
275
85%
8.2.3.
Sample Size Re-estimation
No sample size re-estimation is planned for this study.
8.3.
Data Analysis Considerations
8.3.1.
Analysis Populations
The following populations will be assessed (the analysis population for genotypic and 
phenotypic analyses as well as for health outcomes assessments will be fully described in 
the reporting and analysis plan [RAP]).
Intent-to-Treat Exposed (ITT-E) Population
This population will consist of all randomised subjects who receive at least one dose of 
study medication. Subjects will be assessed according to their randomised treatment, 
regardless of the treatment they receive. Unless stated otherwise, the ITT-E population 
will be used for summaries of efficacy.
Safety Population
The Safety Population is defined as all subjects who receive at least one dose of IP. 
Subjects will be analyzed according to the actual treatments received.
Per-Protocol Population
This population will consist of subjects in the ITT-E population with the exception of 
major protocol violators: e.g. violations which could affect the assessment of antiviral 
activity. The per protocol (PP) population will be used for sensitivity analyses of the 
primary efficacy endpoint.


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ITT Population
This population will consist of all randomized subjects. Subjects will be assessed 
according to their randomized treatment even if no study treatment was taken or the 
wrong treatment was received.
8.3.2.
Analysis Data Sets
For the primary efficacy analysis, each subjects responses (e.g. <50 c/mL) will be 
calculated according to the FDA’s Snapshot algorithm. This algorithm treats all subjects 
without HIV RNA data at the visit of interest (due to missing data or discontinuation of 
IP prior to visit window) as non-responders, as well as subjects who switch their 
concomitant ART prior to the visit of interest as follows in certain scenarios. However, 
since changes in ART are not permitted in this protocol, all such subjects who change 
ART will be considered non-responders. Otherwise, virologic success or failure will be 
determined by the last available HIV-1 RNA assessment while the subject is on-treatment 
within the visit of interest window (to be specified in the RAP). Full details on this 
Snapshot algorithm will be contained in the RAP.
The observed case (OC) dataset, which uses only data that is available at a particular 
timepoint with no imputation for missing values, will be the primary dataset for assessing 
safety and will also be used for some analyses of efficacy and health outcomes.
A last observation carried forward (LOCF) dataset in which missing values will be 
carried forward from previous, non-missing available on treatment assessments will be 
used in the analysis of health outcomes data. Further details will be provided in the RAP.
8.3.3.
Treatment Comparisons
8.3.3.1.
Primary Comparisons of Interest
The primary analysis will be based on the ITT-E population using the Snapshot dataset. 
The primary comparison will be made at a one-sided 2.5% level of significance. 
Treatment with DTG/ABC/3TC FDC will be declared non-inferior to treatment with 
ATV+RTV+TDF/FTC FDC if the lower end of a two-sided 95% confidence interval for 
the difference between the two groups in response rates at Week 48 lies above -12%.
8.3.3.2.
Other Comparisons of Interest
The analysis described above will also be performed using the PP population and the 
results will be compared for consistency with the results from the ITT-E population. If 
both analyses show non-inferiority then the hypothesis that the antiviral effect of 
treatment with DTG/ABC/3TC FDC is superior to treatment with ATV+RTV+TDF/FTC 
FDC will also be tested in the ITT-E population at the two-sided 5% level of significance. 
Superiority will be declared if the lower end of the 95% confidence interval calculated in 
the ITT-E analysis is above 0%.  The primary comparison will also be performed using 
the ITT population and will be compared for consistency with the results from the ITT-E 
and PP populations.


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8.3.4.
Interim Analysis
The main analysis will be conducted to evaluate the primary objective of the protocol 
when all subjects have completed their Week 48 visit.  Further data cuts and analyses 
may be conducted as necessary in order to support regulatory submissions and 
publications. 
8.3.5.
Key Elements of Analysis Plan
The study design is open-label however the central GSK team responsible for the conduct 
and analysis of the study will not review any summaries of data grouped by treatment 
prior to database freeze for the primary Week 48 analysis.
8.3.5.1.
Efficacy Analyses
For the primary comparison, adjusted estimates of the difference in the rate of responders 
between the two arms will be presented along with CIs based on a stratified analysis 
using Cochran-Mantel-Haenszel (CMH) weights. All CIs will be two-sided. For the 
statistical analysis, four strata (subgroups) will be formed according to the combinations 
of levels of the following categorical variables: Baseline plasma HIV-1 RNA 
(≤vs. >100,000 c/ml) and Baseline CD4+ cell count (≤ vs. >350 cells/mm3).
The CMH estimate of the common difference in rates across strata will be calculated as 
the weighted average of the strata-specific estimates of the difference in response rates 
between the two arms as follows:
• If nk is the number of DTG/ABC/3TC FDC treated subjects, mk is the number 
of ATV+RTV+TDF/FTC FDC treated subjects, and Nk = nk + mk is the total 
number of subjects in the kth stratum, then the CMH estimate is given by



k
k
k
cmh
W
d
W
d
ˆ
ˆ
where
k
k
k
k
N
m
n
W 
are CMH weights and 
k
dˆ
are estimates of the differences in response rates 
between the two treatment arms, rd-ra, for the kth strata. 
The corresponding two-sided 95% CI will be calculated as
)
ˆ
r(
aˆv
96
.1
ˆ
cmh
cmh
d
d




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using the variance estimator 
)
ˆ
r(
aˆ
v
cmh
d
, given by [Sato, 1989], which is consistent in both 
sparse data and large strata.  The full equation for this variance estimate is provided in the 
RAP.
The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to test for one-
way homogeneity across the levels of each categorical variable, with each categorical 
variable considered separately. Following Lui and Kelly [Lui, 2000], ½ will be added to 
each cell in any strata for which the stratum-specific rate estimates of either rd or ra are 
zero, and tests will be one-sided. Full details will be contained in the RAP. Any 
heterogeneity found to be statistically significant will be explored and if necessary results 
will be reported for each level of the categorical variable. Investigation of heterogeneity 
will be confined to the primary endpoint using the Week 48 Snapshot analysis. Tests of 
homogeneity will be assessed at the one-sided 10% level of significance.
Secondary analyses of plasma HIV-1 RNA and CD4+ cell count will be analyzed over 
time using the OC analysis dataset. The proportion of subjects with HIV-1 RNA below 
50/400 copies/ml over time will be presented using both the Snapshot and OC datasets. 
The incidence of HIV-1 disease progression (AIDS and death) will be presented.  Further 
details of secondary efficacy analyses will be included in the RAP.
Data gathered after subjects withdraw from IP will be listed but will not be included in 
summary tables. Data will be allocated to visit windows using actual visit dates rather 
than nominal visit numbers. Data collected from extra visits within a window will be 
listed and will be included in the derivation of the Snapshot response at analysis visits of 
interest, but summary tables using OC datasets will only use the data captured closest to 
the target visit date. Detailed explanations of the derivation of visit windows will be 
included in the RAP. Any deviations from planned analyses will be detailed in the 
clinical study report (CSR).
8.3.5.2.
Safety Analyses
Exposure to study medication, measured by the number of weeks on study drug, will be 
summarized by treatment group. The proportion of subjects reporting AEs will be 
tabulated for each treatment group. The following summaries of AEs will be provided:

Incidence and severity of all AEs

Incidence and severity of treatment related AEs

Incidence and severity of AEs leading to withdrawal

Incidence of SAEs
Laboratory and vital signs data will be summarized by visit and treatment group. In 
addition, the number and percentage of subjects with graded laboratory toxicities (based 
on DAIDS categories) will be summarized by treatment group. The proportion of 
subjects experiencing changes from Baseline in their National Cholesterol Education 
Program (NCEP) lipid categories will be summarized by treatment arm.


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Renal markers and bone markers will be summarized by visit and treatment group based 
on an OC dataset.  Cardiovascular risk based on Framingham score will be summarized 
at Baseline based on an OC dataset. 
Further details of safety analyses will be included in the RAP.
8.3.5.3.
Health Outcomes Analyses
The SF-12 includes one scale measuring each of 8 health domains: physical functioning, 
role participation with physical health problems (role physical), bodily pain, general 
health, vitality, social functioning, role participation with emotional health problems and 
mental health, with two factors for health status: one for physical component summary 
(PCS) and mental component summary (MCS).
Changes from Baseline in scores for PCS and the MCS will be compared between the 
two treatment arms at each time point. Exploratory analysis will be done to assess which 
aspects of health are most impacted at the item level and health domain level.
The HIVTSQ was developed to evaluate treatments for HIV and patient satisfaction. The 
higher the score, the greater the improvement in treatment satisfaction as compared to the 
past few weeks. A smaller score represents a decline in treatment satisfaction compared 
to the past few weeks. 
The HIVTSQ items are summed up to produce a treatment satisfaction score (0 to 60) 
and an individual satisfaction rating for each item (0 to 6) and two subscales: general 
satisfaction/clinical and lifestyle/ease subscales. These scores will be summarized and 
compared between the treatment groups in an exploratory analysis at each time point.
8.3.5.4.
Viral Genotyping/Phenotyping Analyses
The incidence of treatment emergent genotypic and phenotypic resistance to NRTIs, 
protease inhibitors, and INIs will be summarized by treatment arm. Details of the 
analyses to be performed will be specified in the RAP.
8.3.5.5.
Pharmacogenetic Analyses
See Appendix 3 (Section 11.3) for details about the Pharmacogenetics Analysis Plan.
9.
STUDY CONDUCT CONSIDERATIONS
9.1.
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.


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9.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a study site, GSK will obtain favorable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with ICH GCP and 
applicable country-specific regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with ICH GCP, all applicable subject privacy 
requirements, and the ethical principles that are outlined in the Declaration of Helsinki 
2008, including, but not limited to:

IRB/IEC review and favorable opinion/approval of study protocol and any 
subsequent amendments.

Subject informed consent.

Investigator reporting requirements.
GSK will provide full details of the above procedures, either verbally, in writing, or both.
Written informed consent must be obtained from each subject prior to participation in the 
study.
In approving the clinical protocol the IEC/IRB and, where required, the applicable 
regulatory agency are also approving the optional assessments e.g., PGx assessments 
described in Appendix 3, Section 11.3, unless otherwise indicated.  Where permitted by 
regulatory authorities, approval of the optional assessments can occur after approval is 
obtained for the rest of the study.  If so, then the written approval will clearly indicate 
approval of the optional assessments is being deferred and the study, except for the 
optional assessments, can be initiated.  When the optional assessments are not approved, 
then the approval for the rest of the study will clearly indicate this and therefore, the 
optional assessments will not be conducted.
9.3.
Quality Control (Study Monitoring)
In accordance with applicable regulations, GCP, and GSK procedures, GSK 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 GSK 
requirements.  When reviewing data collection procedures, the discussion will include 
identification, agreement and documentation of data items for which the CRF will serve 
as the source document.
GSK will monitor the study to ensure that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.


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
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.
9.4.
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 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.
9.5.
Study and Site Closure
Unless terminated early, this study will be considered completed after the last subject 
completes the last study-related clinic visit or assessment.  
Upon completion or termination of the study, the GSK monitor will conduct site closure 
activities with the investigator or site staff (as appropriate), in accordance with applicable 
regulations, GCP, and GSK Standard Operating Procedures.
GSK reserves the right to temporarily suspend or terminate the study at any time for 
reasons including (but not limited to) safety issues, ethical issues, or severe non-
compliance.  If GSK determines that such action is required, GSK will discuss the 
reasons for taking such action with the investigator or head of the medical institution 
(where applicable).  When feasible, GSK will provide advance notice to the investigator 
or head of the medical institution of the impending action.
If a study is suspended or terminated for safety reasons, GSK will promptly inform all 
investigators, heads of the medical institutions (where applicable),and/or institutions 
conducting the study.  GSK will also promptly inform the relevant regulatory authorities 
of the suspension/termination along with the reasons for such action.  Where required by 
applicable regulations, the investigator or head of the medical institution must inform the 
IRB/IEC promptly and provide the reason(s) for the suspension/termination.
9.6.
Records Retention
Following closure of the study, the investigator or head of the medical institution (where 
applicable) must maintain all site study records (except for those required by local 
regulations to be maintained elsewhere) in a safe and secure location.  The records must 
be easily accessible when needed (e.g., for a GSK audit or regulatory inspection) and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.


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Where permitted by local laws/regulations or institutional policy, some or all of the 
records may be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution must 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.  In addition, they must meet accessibility and retrieval standards, 
including regeneration of a hard copy, if required.  The investigator must also ensure that 
an acceptable back-up of the reproductions exists and that there is an acceptable quality 
control procedure in place for creating the reproductions.
GSK will inform the investigator of the time period for retaining the site records in order 
to comply with all applicable regulatory requirements.  The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by local
laws/regulations, GSK standard operating procedures, and/or institutional requirements.
The investigator must notify GSK of any changes in the archival arrangements, including, 
but not limited to archival of records at an off-site facility or transfer of ownership of the 
records in the event that the investigator is no longer associated with the site.
9.7.
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 CSR.  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 GSK site or other mutually-agreeable location.
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The results summary will be posted to the Clinical Study Register no later than eight 
months after the final primary completion date, the date that the final subject was 
examined or received an intervention for the purposes of final collection of data for the 
primary outcome.  In addition, a manuscript will be submitted to a peer reviewed journal 
for publication no later than 18 months after the last subject’s last visit (LSLV).  When 
manuscript publication in a peer reviewed journal is not feasible, a statement will be 
added to the register to explain the reason for not publishing.


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10.
REFERENCES
Atripla Product Information, April 2013 
Centers for Disease Control and Prevention (CDC) 1993 revised classification system for 
HIV infection and expanded surveillance case definition for AIDS among adolescents 
and adults.  MMWR 1992;41(No. RR-17):1-19.
Cockroft DW, Gault MH.  Pediction of creatinine clearance from serum creatinine.  
Nephron 1976;16:31-41.
Complera US Product Information, January, 2013
Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of 
raltegravir for resistant HIV-1 Infection. N Engl J Med. 2008;359:355-65. 
Currier J, Averitt Bridge D, Hagins D.  Sex-Based Outcomes of Darunavir–Ritonavir 
Therapy: The GRACE (Gender, Race, and Clinical Experience) Study; Ann Intern Med. 
2010; 153(6): 349–357. doi:  10.1059/0003-4819-153-6-201009210-00002
DeJesus E, Rockstroh JK, Henry K, et al.  Co-formulated elvitegravir, cobicistat, 
emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus 
co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of 
HIV-1 infection: a randomized, double-blind, phase 3, non-inferiority trial.  Lancet
2012;379(9835):2429–2438.
Department of Health and Human Services (US DHHS) Food and Drug Administration 
Center for Drug Evaluation and Research (CDER). Guidance for Industry. Antiretroviral 
Drugs Using Plasma HIV RNA Measurements - Clinical Considerations for Accelerated 
and Traditional Approval.  October 2002
Department of Health and Human Services (US DHHS). Panel on Antiretroviral 
Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in 
HIV-1-infected adults and adolescents. Updated February 12, 2013. Available at 
http://www.aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. 
European AIDS Clinical Society (EACS) Guidelines for the clinical management and 
treatment of HIV Infected Adults in Europe, 2012. Available at 
http://www.europeanaidsclinicalsociety.org/images/stories/EACS-Pdf/EacsGuidelines-
v6.1-2edition.pdf.
Fleiss J.L. Statistical Methods for Rates and Proportions. 2 ed. New York:John Wiley; 
1981.  
GlaxoSmithKline Document Number 2017N352880_00: GSK1349572 Clinical 
Investigator's Brochure, Version 11, Supplement 01, December 2017.


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GlaxoSmithKline Document Number 2017N352880_01: GSK1349572 Clinical 
Investigator's Brochure, Version 11, Supplement 02, June 2018.
GlaxoSmithKline Document Number RM2007/00683/11: GSK1349572 Clinical 
Investigator's Brochure. Version 11, October 2017.
Hazuda DJ, Miller MD, Nguyen BY and Zhao J. Resistance to the HIV-integrase 
inhibitor raltegravir: Analysis of Protocol 005, a Phase II study in patients with triple-
class resistant HIV-1 infection. Abstract 8, XVI International HIV Drug Resistance 
Workshop. Antiviral Therapy. 2007a;12:510. 
Hill, A, Sabin, C. Designing and interpreting noninferiority trials in naïve and
experienced patients. AIDS. 2008;22(8):913-921.
International AIDS Society (IAS)–USA Antiretroviral Treatment of Adult HIV Infection: 
2010 Recommendations of the International AIDS Society-USA Panel. Thompson et al. 
JAMA. 2012;308(4):387-402.
International AIDS Society (IAS)–USA. Update of the Drug Resistant Mutations in 
HIV-1: March 2013. Topics in HIV Medicine 2013;21(1): 6-14.
Isentress EU Summary of Product Characteristics, March 2013
Isentress US Product Information, April 2013; 
Lennox JL, DeJesus E, Berger DS, et al.  Raltegravir Versus Efavirenz Regimens in 
Treatment-Naive HIV-1–Infected Patients: 96-Week Efficacy, Durability, Subgroup, 
Safety, and Metabolic Analyses. J Acquir Immune Defic Syndr 2010;55(1):39-48.
Lui K.-J., Kelly C. A Revisit on Tests for Homogeneity of the Risk Difference. 
Biometrics. 2000;56:309-315.
McColl DJ, Fransen S, Gupta S, et al. Resistance and cross-resistance to first generation 
integrase inhibitors:  Insights from a Phase II study of elvitegravir (GS-9137).  Abstract 
9, XVI International HIV Drug Resistance Workshop. Antiviral Therapy. 2007;12:S11. 
Molina J, LaMarca A, Andrade-Villanueva J, et al.  Efficacy and safety of once daily 
elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 
receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-
inferiority study.  Lancet Infect Dis 2012;12: 27–35.
Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/Ritonavir 
versus twice-daily lopinavir/Ritonavir, each in combination with tenofovir and 
Emtricitabine, for management of antiretroviral-naïve HIV-1-infected patients: 48 week 
efficacy and safety results of the CASTLE study. Lancet. 2008; 372; 646-655.
Oquendo MA, Mann J. Risk Factors for suicidal behaviour : utility and limitations of 
research instruments (2003). In M.B. First [Ed] Standardized Evaluation in Clinical 
Practice, pp 103- 130.


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Paterson D, Swindells S, Mohr J, et. al. How Much Adherence is Enough? A Prospective 
Study of Adherence to Protease Inhibitor Therapy Using MEMSCaps. Abstract 92, 6th 
Conference on Retrovirus and Opportunistic Infections. 1999; 84.
Reyataz EU Summary of Product Characteristics, September 2012.
Reyataz US Product Information, April 2013.
Sato T. On the variance estimator for the Mantel-Haenszel risk difference. Biometrics. 
1989;45:1323-1324. 
Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, 
and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial 
treatment of HIV-1 infection: a randomised, double-blind, Phase 3 trial, analysis of 
results after 48 weeks.  Lancet 2012;379 (9835):2439–2448.
Squires KE, Johnson M, Yang R, et al. Comparative gender analysis of the efficacy and 
safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J 
Antimicrob Chemother. 2011; 66: 363-370.
Stribild, Product Information, 2012
Truvada, Product Information, July 2012
Ware JE, Kosinski M, and Keller SD. A 12-Item Short-Form Health Survey: 
Construction of scales and preliminary tests of reliability and validity. Medical Care, 
1996;34(3):220-233. 
Woodcock A, Bradley C (2001). Validation of the HIV Treatment Satisfaction 
Questionnaire (HIVTSQ). Quality of Life Research. 10:517-531.
Woodcock A, Bradley C (2006). Validation of the Revised 10-item HIV Treatment 
Satisfaction Questionnaire Status Version and New Change Version . Value in Health.
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11.
APPENDICES
11.1.
Appendix 1: CDC Classification System for HIV-1 Infections 
(1993)
Reference - 1993 revised classification system for HIV infection and expanded 
surveillance case definition for AIDS among adolescents and adults. MMWR 1992;41 
(No. RR-17):1-19.
Clinical Categories
The clinical categories of HIV infection are defined as follows:
Category A
Category A consists of one or more of the conditions listed below in an adolescent or 
adult (>13 years) with documented HIV infection.  Conditions listed in Categories B and 
C must not have occurred.

Asymptomatic HIV infection

Persistent generalized lymphadenopathy

Acute (primary) HIV infection with accompanying illness or history of acute HIV 
infection
Category B (Symptomatic non-AIDS conditions)
Category B consists of symptomatic conditions in an HIV-infected adolescent or adult 
that are not included among conditions listed in clinical Category C and that meet at least 
one of the following criteria:  a) the conditions are attributed to HIV infection or are 
indicative of a defect in cell-mediated immunity; or b) the conditions are considered by 
physicians to have a clinical course or to require management that is complicated by HIV 
infection.  Examples of conditions in clinical Category B include, but are not limited 
to:

Bacillary angiomatosis

Candidiasis, oropharyngeal (thrush)

Candidiasis, vulvovaginal; persistent, frequent, or poorly responsive to therapy

Cervical dysplasia (moderate or severe)/cervical carcinoma in situ

Constitutional symptoms, such as fever (38.5C) or diarrhea lasting >1 month

Hairy leukoplakia, oral

Herpes zoster (shingles), involving at least two distinct episodes or more than one 
dermatome

Idiopathic thrombocytopenic purpura


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
Listeriosis

Pelvic inflammatory disease, particularly if complicated by tubo-ovarian abscess

Peripheral neuropathy
For classification purposes, Category B conditions take precedence over those in 
Category A.  For example, someone previously treated for oral or persistent vaginal 
candidiasis (and who has not developed a Category C disease) but who is now 
asymptomatic should be classified in clinical Category B.
Category C (AIDS indicator conditions as defined by diagnostic or presumptive 
measures).
Category C includes the clinical conditions listed in the AIDS surveillance case 
definition.  For classification purposes, once a Category C condition has occurred, the 
person will remain in Category C.
Conditions in Category C include:

Candidiasis of bronchi, trachea, or lungs

Candidiasis, esophageal

Cervical cancer, invasive

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (>1 month’s duration)

Cytomegalovirus disease (other than liver, spleen, or nodes)

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex:  chronic ulcer(s) (>1 month’s duration);or bronchitis, pneumonitis, 
or esophagitis

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month’s duration)

Kaposi’s sarcoma

Lymphoma, Burkitt’s (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary

Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)

Mycobacterium, other species or unidentified species, disseminated or 
extrapulmonary


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
Pneumocystis carinii pneumonia

Pneumonia, recurrent

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain

Wasting syndrome due to HIV

Non-CDC, HIV-associated conditions.


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11.2.
Appendix 2: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events
VERSION 1.0, DECEMBER 2004; CLARIFICATION AUGUST 2009
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (“DAIDS AE Grading Table”) is a descriptive terminology which can be utilized 
for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE 
term.


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
ESTIMATING SEVERITY GRADE1
Clinical adverse event NOT 
identified elsewhere in this DAIDS 
AE grading table
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
Symptoms causing inability to perform 
basic self-care functions OR Medical or 
operative intervention indicated to 
prevent permanent impairment, 
persistent disability, or death
SYSTEMIC
Acute systemic allergic reaction
Localized urticaria (wheals) with 
no medical intervention indicated
Localized urticaria with medical 
intervention indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild bronchospasm
Acute anaphylaxis OR Life-threatening 
bronchospasm OR laryngeal edema
Chills
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
NA
Fatigue
Malaise
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
Incapacitating fatigue/malaise 
symptoms
causing inability to perform basic self-
care functions
Fever (nonaxillary)
37.7 – 38.6C
38.7 – 39.3C
39.4 – 40.5C
> 40.5C
Pain (indicate body site)
DO NOT use for pain due to 
injection (See Injection Site 
Reactions: Injection site pain)
See also Headache, Arthralgia, 
and Myalgia
Pain causing no or minimal 
interference with usual social & 
functional activities
Pain causing greater than minimal 
interference with usual social & 
functional activities
Pain causing inability to perform 
usual social & functional activities
Disabling pain causing inability to 
perform basic self-care functions OR 
Hospitalization (other than emergency 
room visit) indicated
Unintentional weight loss
NA
5 – 9% loss in body weight from 
baseline
10 – 19% loss in body weight from 
baseline
20% loss in body weight from 
baseline OR Aggressive intervention 
indicated [e.g., tube feeding or total 
parenteral nutrition (TPN)]


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
INFECTION
Infection (any other than HIV 
infection)
Localized, no systemic 
antimicrobial treatment indicated 
AND Symptoms causing no or 
minimal interference with usual 
social & functional activities
Systemic antimicrobial treatment 
indicated OR Symptoms causing 
greater than minimal interference 
with usual social & functional 
activities
Systemic antimicrobial treatment 
indicated AND Symptoms causing 
inability to perform usual social & 
functional activities OR Operative 
intervention (other than simple 
incision and drainage) indicated
Life-threatening consequences (e.g., 
septic shock)
INJECTION SITE REACTIONS
Injection site pain (pain without 
touching)
Or
Tenderness (pain when area is 
touched)
Pain/tenderness causing no or 
minimal limitation of use of limb
Pain/tenderness limiting use of limb 
OR Pain/tenderness causing 
greater than minimal interference 
with usual social & functional 
activities
Pain/tenderness causing inability to 
perform usual social & functional 
activities
Pain/tenderness causing inability to 
perform basic self-care function OR 
Hospitalization (other than emergency 
room visit) indicated for management 
of pain/tenderness
Injection site reaction (localized)
Adult > 15 years
Erythema OR Induration of 5x5 
cm – 9x9 cm (or 25 cm2 – 81cm2)
Erythema OR Induration OR Edema 
> 9 cm any diameter (or > 81 cm2)
Ulceration OR Secondary infection 
OR Phlebitis OR Sterile abscess OR 
Drainage
Necrosis (involving dermis and deeper
tissue)
Pediatric 15 Years
Erythema OR Induration OR 
Edema present but 2.5 cm 
diameter
Erythema OR Induration OR Edema 
> 2.5 cm diameter but < 50% 
surface area of the extremity 
segment (e.g., upper arm/thigh)
Erythema OR Induration OR Edema 
involving 50% surface area of the 
extremity segment (e.g., upper 
arm/thigh) OR Ulceration OR 
Secondary infection OR Phlebitis OR 
Sterile abscess OR Drainage
Necrosis (involving dermis and deeper 
tissue)
Pruritis associated with injection
See also Skin: Pruritis (itching - no 
skin lesions)
Itching localized to injection site 
AND Relieved spontaneously or 
with < 48 hours treatment
Itching beyond the injection site but 
not generalized OR Itching localized 
to injection site requiring 48 hours 
treatment
Generalized itching causing inability 
to perform usual social & functional 
activities
NA


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
SKIN – DERMATOLOGICAL
Alopecia
Thinning detectable by study 
participant (or by caregiver for 
young children and disabled 
adults)
Thinning or patchy hair loss 
detectable by health care provider
Complete hair loss
NA
Cutaneous reaction – rash
Localized macular rash
Diffuse macular, maculopapular, or 
morbilliform rash OR Target lesions
Diffuse macular, maculopapular, or 
morbilliform rash with vesicles or 
limited number of bullae OR 
Superficial ulcerations of mucous 
membrane limited to one site
Extensive or generalized bullous 
lesions OR Stevens-Johnson 
syndrome OR Ulceration of mucous 
membrane involving two or more 
distinct mucosal sites OR Toxic 
epidermal necrolysis (TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized
Marked or generalized
NA
NA
Pruritis (itching – no skin lesions)
(See also Injection Site Reactions: 
Pruritis associated with injection)
Itching causing no or minimal 
interference with usual social & 
functional activities
Itching causing greater than 
minimal interference with usual 
social & functional activities
Itching causing inability to perform 
usual social & functional activities
NA
CARDIOVASCULAR
Cardiac arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND Non-urgent 
medical intervention indicated
Symptomatic, non-life-threatening 
AND Non-urgent medical intervention 
indicated
Life-threatening arrhythmia OR Urgent 
intervention indicated
Cardiac-ischemia/infarction
NA
NA
Symptomatic ischemia (stable 
angina) OR Testing consistent with 
ischemia
Unstable angina OR Acute myocardial 
infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No transfusion 
indicated
Symptomatic AND Transfusion of 2 
units packed RBCs (for children 10 
cc/kg) indicated
Life-threatening hypotension OR 
Transfusion of > 2 units packed RBCs 
(for children >10 cc/kg) indicated
Hypertension
Adult > 17 years
(with repeat testing at same 
visit)
140 – 159 mmHg systolic
OR
90 – 99 mmHg diastolic
160 – 179 mmHg systolic
OR
100 – 109 mmHg diastolic
180 mmHg systolic
OR
110 mmHg diastolic
Life-threatening consequences (e.g., 
malignant hypertension) OR 
Hospitalization indicated (other than 
emergency room visit)


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Pediatric 17 Years
(with repeat testing at same 
visit)
NA
91st – 94th percentile adjusted for 
age, height, and gender (systolic 
and/or diastolic)
95th percentile adjusted for age, 
height, and gender (systolic and/or 
diastolic)
Life-threatening consequences (e.g., 
malignant hypertension) OR 
Hospitalization indicated (other than 
emergency room visit)
Hypotension
NA
Symptomatic, corrected with oral 
fluid replacement
Symptomatic, IV fluids indicated
Shock requiring use of vasopressors or 
mechanical assistance to maintain 
blood pressure
Pericardial effusion
Asymptomatic, small effusion 
requiring no intervention
Asymptomatic, moderate or larger 
effusion requiring no intervention
Effusion with non-life threatening 
physiologic consequences OR 
Effusion with non-urgent intervention 
indicated
Life-threatening consequences (e.g., 
tamponade) OR Urgent intervention 
indicated
Prolonged PR interval
Adult > 16 years
PR interval
0.21 – 0.25 sec
PR interval
> 0.25 sec
Type II 2nd degree AV block OR 
Ventricular pause > 3.0 sec
Complete AV block
Pediatric 16 Years
1st degree AV block (PR > normal 
for age and rate)
Type I 2nd degree AV block
Type II 2nd degree AV block
Complete AV block
Prolonged QTc
Adult > 16 years
Asymptomatic, QTc interval 
0.45-0.47 sec OR Increase 
interval <0.03 sec above baseline
Asymptomatic, QTc interval 
0.48-0.49 sec OR Increase in 
interval 0.03 – 0.05 sec above 
baseline
Asymptomatic, QTc interval 0.50 
sec OR Increase in interval 0.06 
sec above baseline
Life-threatening consequences, e.g., 
Torsade de pointes or other associated 
serious ventricular dysrhythmia
Pediatric 16 years
Asymptomatic, QTc interval 
0.450–0.464 sec
Asymptomatic, QTc interval 
0.465-0.479 sec
Asymptomatic, QTc
interval 0.480 sec
Life-threatening consequences, e.g., 
Torsade de pointes or other associated 
serious ventricular dysrhythmia
Thrombosis/embolism
NA
Deep vein thrombosis AND No 
intervention indicated (e.g., 
anticoagulation, lysis filter, invasive 
procedure)
Deep vein thrombosis AND 
Intervention indicated (e.g., 
anticoagulation, lysis filter, invasive 
procedure)
Embolic event (e.g., pulmonary 
embolism, life-threatening thrombus)
Vasovagal episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness
Present with transient loss of 
consciousness
NA
NA
Ventricular dysfunction 
(congestive heart failure)
NA
Asymptomatic diagnostic finding 
AND intervention indicated
New onset with symptoms OR 
Worsening symptomatic congestive 
heart failure
Life-threatening congestive heart 
failure


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
GASTROINTESTINAL
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated with 
decreased oral intake without 
significant weight loss
Loss of appetite associated with 
significant weight loss
Life-threatening consequences OR 
Aggressive intervention indicated [e.g., 
tube feeding or   total parenteral 
nutrition (TPN)]
Comment: Please note that, while the grading scale provided for Unintentional Weight Loss may be used as a guideline when grading anorexia, this is not a requirement and should 
not be used as a substitute for clinical judgment.
Ascites
Asymptomatic
Symptomatic AND Intervention 
indicated (e.g., diuretics or 
therapeutic paracentesis)
Symptomatic despite intervention
Life-threatening consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or operative 
intervention indicated
Life-threatening consequences (e.g., 
sepsis or perforation)
Constipation
NA
Persistent constipation requiring 
regular use of dietary modifications, 
laxatives, or enemas
Obstipation with manual evacuation 
indicated
Life-threatening consequences (e.g., 
obstruction)
Diarrhea
Adult and
Pediatric 1 year
Transient or intermittent episodes 
of unformed stools OR Increase 
of 3 stools over baseline per 24-
hour period
Persistent episodes of unformed to 
watery stools OR Increase of 4 – 6 
stools over baseline per 24-hour 
period
Bloody diarrhea OR Increase of 7 
stools per 24-hour period OR IV fluid 
replacement indicated
Life-threatening consequences (e.g., 
hypotensive shock)
Pediatric < 1 year
Liquid stools (more unformed 
than usual) but usual number of 
stools
Liquid stools with increased number 
of stools OR Mild dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in severe 
dehydration with aggressive 
rehydration indicated OR Hypotensive 
shock
Dysphagia-
Odynophagia
Symptomatic but able to eat usual 
diet
Symptoms causing altered dietary 
intake without medical intervention 
indicated
Symptoms causing severely altered 
dietary intake with medical 
intervention indicated
Life-threatening reduction in oral intake


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Mucositis/stomatitis (clinical 
exam)
Indicate site (e.g., larynx, oral)
See Genitourinary for 
Vulvovaginitis 
See also Dysphagia-Odynophagia 
and Proctitis
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations
Confluent pseudomembranes or 
ulcerations OR Mucosal bleeding with 
minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal bleeding OR 
Life-threatening consequences (e.g., 
aspiration, choking)
Nausea
Transient (< 24 hours) or 
intermittent nausea with no or 
minimal interference with oral 
intake
Persistent nausea resulting in 
decreased oral intake for 24 – 48 
hours
Persistent nausea resulting in 
minimal oral intake for > 48 hours OR 
Aggressive rehydration indicated 
(e.g., IV fluids)
Life-threatening consequences (e.g., 
hypotensive shock)
Pancreatitis
NA
Symptomatic AND Hospitalization 
not indicated (other than emergency 
room visit)
Symptomatic AND Hospitalization 
indicated (other than emergency 
room visit)
Life-threatening consequences (e.g., 
circulatory failure, hemorrhage, sepsis)
Proctitis (functional-symptomatic)
Also see Mucositis/stomatitis for 
clinical exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities OR 
Medical intervention indicated
Symptoms causing inability to 
perform usual social & functional 
activities OR Operative intervention 
indicated
Life-threatening consequences (e.g., 
perforation)
Vomiting
Transient or intermittent vomiting 
with no or minimal interference 
with oral intake
Frequent episodes of vomiting with 
no or mild dehydration
Persistent vomiting resulting in 
orthostatic hypotension OR 
Aggressive rehydration indicated 
(e.g., IV fluids)
Life-threatening consequences (e.g., 
hypotensive shock)


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
NEUROLOGIC
Alteration in personality-behavior 
or in mood (e.g., agitation, 
anxiety, depression, mania, 
psychosis)
Alteration causing no or minimal 
interference with usual social & 
functional activities
Alteration causing greater than 
minimal interference with usual 
social & functional activities
Alteration causing inability to perform 
usual social & functional activities
Behavior potentially harmful to self or 
others (e.g., suicidal and homicidal 
ideation or attempt, acute psychosis) 
OR Causing inability to perform basic 
self-care functions
Altered Mental Status
For Dementia, see Cognitive and 
behavioral/attentional disturbance 
(including dementia and attention 
deficit disorder)
Changes causing no or minimal 
interference with usual social & 
functional activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social & 
functional activities
Confusion, memory impairment, 
lethargy, or somnolence causing 
inability to perform usual social & 
functional activities
Delirium OR obtundation, OR coma
Ataxia
Asymptomatic ataxia detectable 
on exam OR Minimal ataxia 
causing no or minimal interference 
with usual  social & functional 
activities
Symptomatic ataxia causing greater 
than minimal interference with usual 
social & functional activities
Symptomatic ataxia causing inability 
to perform usual social & functional 
activities
Disabling ataxia causing inability to 
perform basic self-care functions
Cognitive and 
behavioral/attentional disturbance 
(including dementia and attention 
deficit disorder)
Disability causing no or minimal 
interference with usual social & 
functional activities OR 
Specialized resources not 
indicated
Disability causing greater than 
minimal interference with usual 
social & functional activities OR 
Specialized resources on part-time 
basis indicated
Disability causing inability to perform 
usual social & functional activities OR 
Specialized resources on a full-time 
basis indicated
Disability causing inability to perform 
basic self-care functions OR 
Institutionalization indicated
CNS ischemia (acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident (CVA, 
stroke) with neurological deficit
Developmental delay
– Pediatric 16 Years
Mild developmental delay, either 
motor or cognitive, as determined 
by comparison with a 
developmental screening tool 
appropriate for the setting
Moderate developmental delay, 
either motor or cognitive, as 
determined by comparison with a 
developmental screening tool 
appropriate for the setting
Severe developmental delay, either 
motor or cognitive, as determined by 
comparison with a developmental 
screening tool appropriate for the 
setting
Developmental regression, either motor 
or cognitive, as determined by 
comparison with a developmental 
screening tool appropriate for the 
setting


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Headache
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
Symptoms causing inability to perform 
basic self-care functions OR 
Hospitalization indicated (other than 
emergency room visit) OR Headache 
with significant impairment of alertness 
or other neurologic function
Insomnia
NA
Difficulty sleeping causing greater 
than minimal interference with usual 
social & functional activities
Difficulty sleeping causing inability to 
perform usual social & functional 
activities
Disabling insomnia causing inability to 
perform basic self-care functions
Neuromuscular weakness 
(including myopathy & 
neuropathy)
Asymptomatic with decreased 
strength on exam OR Minimal 
muscle weakness causing no or 
minimal interference with usual 
social & functional activities
Muscle weakness causing greater 
than minimal interference with usual 
social & functional activities
Muscle weakness causing inability to 
perform usual social & functional 
activities
Disabling muscle weakness causing 
inability to perform basic self-care 
functions OR Respiratory muscle 
weakness impairing ventilation
Neurosensory Alteration (including 
paresthesia and painful 
neuropathy)
Asymptomatic with sensory 
alteration on exam or minimal 
paresthesia causing no or minimal 
interference with usual social & 
functional activities
Sensory alteration or paresthesia 
causing greater than minimal 
interference with usual social & 
functional activities
Sensory alteration or paresthesia 
causing inability to perform usual 
social & functional activities
Disabling sensory alteration or 
paresthesia causing inability to perform 
basic self-care functions
Seizure: (new onset)
– Adult 18 years
See also Seizure: (known pre-
existing seizure disorder)
NA
1 seizure
2 – 4 seizures
Seizures of any kind which are 
prolonged, repetitive (e.g., status 
epilepticus), or difficult to control (e.g., 
refractory epilepsy)
Seizure: (known pre-existing 
seizure disorder)
– Adult 18 years
For worsening of existing epilepsy 
the grades should be based on an 
increase from previous level of 
control to any of these levels.
NA
Increased frequency of pre-existing 
seizures (non-repetitive) without 
change in seizure character OR 
Infrequent break-through seizures 
while on stable medication in a 
previously controlled seizure 
disorder
Change in seizure character from 
baseline either in duration or quality 
(e.g., severity or focality)
Seizures of any kind which are 
prolonged, repetitive (e.g., status 
epilepticus), or difficult to control (e.g., 
refractory epilepsy)


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Seizure
– Pediatric < 18 years
Seizure, generalized onset with or 
without secondary generalization, 
lasting < 5 minutes with < 24 
hours post ictal state
Seizure, generalized onset with or 
without secondary generalization, 
lasting 5 – 20 minutes with <24 
hours post ictal state
Seizure, generalized onset with or 
without secondary generalization, 
lasting >20 minutes
Seizure, generalized onset with or 
without Secondary generalization, 
requiring intubation and sedation
Syncope (not associated with a 
procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or minimal 
interference with usual social & 
functional activities
Vertigo causing greater than 
minimal interference with usual 
social & functional activities
Vertigo causing inability to perform 
usual social & functional activities
Disabling vertigo causing inability to 
perform basic self-care Functions
RESPIRATORY
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70-80%
FEV1 or peak flow 50–69%
FEV1 or peak flow 25–49%
Cyanosis OR FEV1 or peak flow < 25% 
OR Intubation
Dyspnea or respiratory distress
Adult 14 years
Dyspnea on exertion with no or 
minimal interference with usual 
social & functional activities
Dyspnea on exertion causing 
greater than minimal interference 
with usual social & functional 
activities
Dyspnea at rest causing inability to 
perform usual social & functional 
activities
Respiratory failure with ventilatory 
support Indicated
Pediatric < 14 years
Wheezing OR minimal increase in 
respiratory rate for age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 90 –
95%
Dyspnea at rest causing inability to 
perform usual social & functional 
activities OR Pulse oximetry < 90%
Respiratory failure with ventilatory 
support indicated
MUSCULOSKELETAL
Arthralgia
See also Arthritis
Joint pain causing no or minimal 
interference with usual social & 
functional activities
Joint pain causing greater than 
minimal interference with usual 
social & functional activities
Joint pain causing inability to perform 
usual social & functional activities
Disabling joint pain causing inability to 
perform basic self-care Functions
Arthritis
See also Arthralgia
Stiffness or joint swelling causing 
no or minimal interference with 
usual social & functional activities
Stiffness or joint swelling causing 
greater than minimal interference 
with usual social & functional 
activities
Stiffness or joint swelling causing 
inability to perform usual social & 
functional activities
Disabling joint stiffness or swelling 
causing inability to perform basic self-
care functions


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Bone Mineral Loss
Adult 21 years
BMD t-score -2.5 to -1.0
BMD t-score < -2.5
Pathological fracture (including loss 
of vertebral height)
Pathologic fracture causing life-
threatening Consequences
Pediatric < 21 years
BMD z-score -2.5 to -1.0
BMD z-score < -2.5
Pathological fracture (including loss 
of vertebral height)
Pathologic fracture causing life-
threatening Consequences
Myalgia (non-injection site)
Muscle pain causing no or 
minimal interference with usual 
social & functional activities
Muscle pain causing greater than 
minimal interference with usual 
social & functional activities
Muscle pain causing inability to 
perform usual social & functional 
activities
Disabling muscle pain causing inability 
to perform basic self-care functions
Osteonecrosis
NA
Asymptomatic with radiographic 
findings AND No operative 
intervention indicated
Symptomatic bone pain with 
radiographic findings OR Operative 
intervention indicated
Disabling bone pain with radiographic 
findings causing inability to perform 
basic self-care functions
GENITOURINARY
Cervicitis (symptoms)
(For use in studies evaluating 
topical study agents)
For other cervicitis see Infection: 
Infection (any other than HIV 
infection)
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
Symptoms causing inability to perform 
basic self-care functions
Cervicitis (clinical exam)
(For use in studies evaluating 
topical study agents)
For other cervicitis see Infection: 
Infection (any other than HIV 
infection)
Minimal cervical abnormalities on 
examination (erythema,
Mucopurulent discharge, or 
friability) OR Epithelial disruption < 
25% of total surface
Moderate cervical abnormalities on 
examination (erythema, 
mucopurulent discharge, or 
friability) OR Epithelial disruption of 
25 – 49% total surface
Severe cervical abnormalities on 
examination (erythema, 
mucopurulent discharge, or friability) 
OR Epithelial disruption 50 – 75% 
total surface
Epithelial disruption > 75% total 
surface
Inter-menstrual bleeding (IMB)
Spotting observed by participant
OR Minimal blood observed 
during clinical or colposcopic 
examination
Inter-menstrual bleeding not greater 
in duration or amount than usual 
menstrual cycle
Inter-menstrual bleeding greater in 
duration or amount than usual 
menstrual cycle
Hemorrhage with life-threatening 
hypotension OR Operative intervention 
indicated


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Urinary tract obstruction (e.g., 
stone)
NA
Signs or symptoms of urinary tract 
obstruction without hydronephrosis 
or renal dysfunction
Signs or symptoms of urinary tract 
obstruction with hydronephrosis or 
renal dysfunction
Obstruction causing life-threatening 
consequences
Vulvovaginitis (symptoms)
(Use in studies evaluating topical 
study agents) 
For other vulvovaginitis see 
Infection: Infection (any other than 
HIV infection)
Symptoms causing no or minimal 
interference with usual social & 
functional activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & functional 
activities
Symptoms causing inability to perform 
basic self-care functions
Vulvovaginitis (clinical exam)
(Use in studies evaluating topical 
study agents)
For other vulvovaginitis see 
Infection: Infection (any other than 
HIV infection)
Minimal vaginal abnormalities on 
examination OR Epithelial 
disruption <25% of total surface
Moderate vaginal abnormalities on 
examination OR Epithelial 
disruption of 25 - 49% total surface
Severe vaginal abnormalities on 
examination OR Epithelial disruption 
50 - 75% total surface
Vaginal perforation OR Epithelial 
disruption > 75% total surface
OCULAR/VISUAL
Uveitis
Asymptomatic but detectable on 
exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR Operative 
intervention indicated
Disabling visual loss in affected eye(s)
Visual changes (from baseline)
Visual changes causing no or 
minimal interference with usual 
social & functional activities
Visual changes causing greater 
than minimal interference with usual 
social & functional activities
Visual changes causing inability to 
perform usual social & functional 
activities
Disabling visual loss in affected eye(s)
ENDOCRINE/METABOLIC
Abnormal fat accumulation (e.g., 
back of neck, breasts, abdomen)
Detectable by study participant (or 
by caregiver for young children
and disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious changes on 
casual visual inspection
NA
Diabetes mellitus
NA
New onset without need to initiate 
medication OR Modification of 
current medications to regain 
glucose control
New onset with initiation of 
medication indicated OR Diabetes 
uncontrolled despite treatment 
modification
Life-threatening consequences (e.g., 
ketoacidosis, hyperosmolar non-ketotic 
coma)


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CLINICAL
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY LIFE-THREATENING
Gynecomastia
Detectable by study participant or 
caregiver (for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on casual 
visual inspection
NA
Hyperthyroidism
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid suppression therapy 
indicated
Symptoms causing inability to 
perform usual social & functional 
activities OR Uncontrolled despite 
treatment modification
Life-threatening consequences (e.g., 
thyroid storm)
Hypothyroidism
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid replacement therapy 
indicated
Symptoms causing inability to 
perform usual social & functional 
activities OR Uncontrolled despite 
treatment modification
Life-threatening consequences (e.g., 
myxedema coma)
Lipoatrophy (e.g., fat loss from the 
face, extremities, buttocks)
Detectable by study participant (or 
by caregiver for young children 
and disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on casual 
visual inspection
NA
1.
Basic Self-care Functions – Adult: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding.
Basic Self-care Functions – Young Children: Activities that are age and culturally appropriate (e.g., feeding self with culturally appropriate eating implement).
Usual Social & Functional Activities – Adult: Adaptive tasks and desirable activities, such as going to work, shopping, cooking, use of transportation, pursuing a hobby, etc.
Usual Social & Functional Activities – Young Children: Activities that are age and culturally appropriate (e.g., social interactions, play activities, learning tasks, etc.).


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
HEMATOLOGY
Standard International Units are listed in italics
Absolute CD4+ count
– Adult and Pediatric
> 13 years
(HIV NEGATIVE ONLY)
300 – 400/mm3
300 – 400/µL
200 – 299/mm3
200 – 299/µL
100 – 199/mm3
100 – 199/µL
< 100/mm3
< 100/µL
Absolute lymphocyte
count
– Adult and Pediatric
> 13 years
(HIV NEGATIVE ONLY)
600 – 650/mm3
0.600 x 109 –
0.650 x 109/L
500 – 599/mm3
0.500 x 109 –
0.599 x 109/L
350 – 499/mm3
0.350 x 109 –
0.499 x 109/L
< 350/mm3
< 0.350 x 109/L
Comment:  Values in children 13 years are not given for the two parameters above because the absolute counts are variable.
Absolute neutrophil count (ANC)
Adult and Pediatric,
> 7 days
1,000 – 1,300/mm3
1.000 x 109 –
1.300 x 109/L
750 – 999/mm3
0.750 x 109 –
0.999 x 109/L
500 – 749/mm3
0.500 x 109 –
0.749 x 109/L
< 500/mm3
< 0.500 x 109/L
Infant*†, 2 – 7 days
1,250 – 1,500/mm3
1.250 x 109 –
1.500 x 109/L
1,000 – 1,249/mm3
1.000 x 109 –
1.249 x 109/L
750 – 999/mm3
0.750 x 109 –
0.999 x 109/L
< 750/mm3
< 0.750 x 109/L
Infant*†, 1 day
4,000 – 5,000/mm3
4.000 x 109 –
5.000 x 109/L
3,000 – 3,999/mm3
3.000 x 109 –
3.999 x109/L
1,500 – 2,999/mm3
1.500 x 109 –
2.999 x 109/L
< 1,500/mm3
< 1.500 x 109/L
Fibrinogen, decreased
100 – 200 mg/dL
1.00 – 2.00 g/L
OR
0.75 – 0.99 x LLN
75 – 99 mg/dL
0.75 – 0.99 g/L
OR
0.50 – 0.74 x LLN
50 – 74 mg/dL
0.50 – 0.74 g/L
OR
0.25 – 0.49 x LLN
< 50 mg/dL
< 0.50 g/L
OR
< 0.25 x LLN
OR
Associated with gross bleeding


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Hemoglobin (Hgb)
Adult and Pediatric
57 days
(HIV POSITIVE ONLY)
8.5 – 10.0 g/dL
5.24 – 6.23 mmol/L
7.5 – 8.4 g/dL
4.62 – 5.23 mmol/L
6.50 – 7.4 g/dL
4.03 – 4.61 mmol/L
< 6.5 g/dL
< 4.03 mmol/L
Adult and Pediatric
57 days
(HIV NEGATIVE ONLY)
10.0 – 10.9 g/dL
6.18 – 6.79 mmol/L
OR
Any decrease
2.5 – 3.4 g/dL
1.58 – 2.13 mmol/L
9.0 – 9.9 g/dL
5.55 – 6.17 mmol/L
OR
Any decrease
3.5 – 4.4 g/dL
2.14 – 2.78 mmol/L
7.0 – 8.9 g/dL
4.34 – 5.54 mmol/L
OR
Any decrease
4.5 g/dL
2.79 mmol/L
< 7.0 g/dL
< 4.34 mmol/L
Infant*†, 36 – 56 days
(HIV POSITIVE OR NEGATIVE)
8.5 – 9.4 g/dL
5.24 – 5.86 mmol/L
7.0 – 8.4 g/dL
4.31 – 5.23 mmol/L
6.0 – 6.9 g/dL
3.72 – 4.30 mmol/L
< 6.00 g/dL
< 3.72 mmol/L
Infant*†, 22 – 35 days
(HIV POSITIVE OR NEGATIVE)
9.5 – 10.5 g/dL
5.87 – 6.54 mmol/L
8.0 – 9.4 g/dL
4.93 – 5.86 mmol/L
7.0 – 7.9 g/dL
4.34 – 4.92 mmol/L
< 7.00 g/dL
< 4.34 mmol/L
Infant*†, 21 days
(HIV POSITIVE OR NEGATIVE)
12.0 – 13.0 g/dL
7.42 – 8.09 mmol/L
10.0 – 11.9 g/dL
6.18 – 7.41 mmol/L
9.0 – 9.9 g/dL
5.59 – 6.17 mmol/L
< 9.0 g/dL
< 5.59 mmol/L
International Normalized
Ratio of prothrombin time
(INR)
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.1 – 3.0 x ULN
> 3.0 x ULN
Methemoglobin
5.0 – 10.0%
10.1 – 15.0%
15.1 – 20.0%
> 20.0%
Prothrombin Time (PT)
1.1 – 1.25 x ULN
1.26 – 1.50 x ULN
1.51 – 3.00 x ULN
> 3.00 x ULN
Partial Thromboplastin
Time (PTT)
1.1 – 1.66 x ULN
1.67 – 2.33 x ULN
2.34 – 3.00 x ULN
> 3.00 x ULN
Platelets, decreased
100,000 –
124,999/mm3
100.000 x 109 –
124.999 x 109/L
50,000 –
99,999/mm3
50.000 x 109 –
99.999 x 109/L
25,000 –
49,999/mm3
25.000 x 109 –
49.999 x 109/L
< 25,000/mm3
< 25.000 x 109/L
WBC, decreased
2,000 – 2,500/mm3
2.000 x 109 –
2.500 x 109/L
1,500 – 1,999/mm3
1.500 x 109 –
1.999 x 109/L
1,000 – 1,499/mm3
1.000 x 109 –
1.499 x 109/L
< 1,000/mm3
< 1.000 x 109/L


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
CHEMISTRIES
Standard International Units are listed in italics
Acidosis
NA
pH < normal, but 7.3
pH < 7.3 without life-threatening 
consequences
pH < 7.3 with life-threatening 
consequences
Albumin, serum, low
3.0 g/dL – < LLN
30 g/L – < LLN
2.0 – 2.9 g/dL
20 – 29 g/L
< 2.0 g/dL
< 20 g/L
NA
Alkaline Phosphatase
1.25 – 2.5 x ULN†
2.6 – 5.0 x ULN†
5.1 – 10.0 x ULN†
> 10.0 x ULN†
Alkalosis
NA
pH > normal, but 7.5
pH > 7.5 without life-threatening 
consequences
pH > 7.5 with life-threatening 
consequences
ALT (SGPT)
1.25 – 2.5 x ULN
2.6 – 5.0 x ULN
5.1 – 10.0 x ULN
> 10.0 x ULN
AST (SGOT)
1.25 – 2.5 x ULN
2.6 – 5.0 x ULN
5.1 – 10.0 x ULN
> 10.0 x ULN
Bicarbonate, serum, low
16.0 mEq/L – < LLN
16.0 mmol/L – < LLN
11.0 – 15.9 mEq/L
11.0 – 15.9 mmol/L
8.0 – 10.9 mEq/L
8.0 – 10.9 mmol/L
< 8.0 mEq/L
< 8.0 mmol/L
Bilirubin (Total)
Adult and Pediatric >14 days
1.1 – 1.5 x ULN
1.6 – 2.5 x ULN
2.6 – 5.0 x ULN
> 5.0 x ULN
Infant*†, 14 days (non-
hemolytic)
NA
20.0 – 25.0 mg/dL
342 – 428 µmol/L
25.1 – 30.0 mg/dL
429 – 513 µmol/L
> 30.0 mg/dL
> 513.0 µmol/L
Infant*†, 14 days (hemolytic)
NA
NA
20.0 – 25.0 mg/dL
342 – 428 µmol/L
> 25.0 mg/dL
> 428 µmol/L
Calcium, serum, high (corrected for albumin)
Adult and Pediatric 7 days
10.6 – 11.5 mg/dL
2.65 – 2.88 mmol/L
11.6 – 12.5 mg/dL
2.89 – 3.13 mmol/L
12.6 – 13.5 mg/dL
3.14 – 3.38 mmol/L
> 13.5 mg/dL
> 3.38 mmol/L
Infant*†, < 7 days
11.5 – 12.4 mg/dL
2.88 – 3.10 mmol/L
12.5 – 12.9 mg/dL
3.11 – 3.23 mmol/L
13.0 – 13.5 mg/dL
3.245 – 3.38 mmol/L
> 13.5 mg/dL
> 3.38 mmol/L
Calcium, serum, low 
Adult and Pediatric 7 days
7.8 – 8.4 mg/dL
1.95 – 2.10 mmol/L
7.0 – 7.7 mg/dL
1.75 – 1.94 mmol/L
6.1 – 6.9 mg/dL
1.53 – 1.74 mmol/L
< 6.1 mg/dL
< 1.53 mmol/L
Infant*†, < 7 days
6.5 – 7.5 mg/dL
1.63 – 1.88 mmol/L
6.0 – 6.4 mg/dL
1.50 – 1.62 mmol/L
5.50 – 5.90 mg/dL
1.38 – 1.51 mmol/L
< 5.50 mg/dL
< 1.38 mmol/L
Cardiac troponin I (cTnI)
NA
NA
NA
Levels consistent with myocardial 
infarction or unstable angina as defined 
by the manufacturer


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Cardiac troponin T (cTnT)
NA
NA
NA
0.20 ng/mL
OR
Levels consistent with myocardial 
infarction or unstable angina as defined 
by the manufacturer
Cholesterol (fasting)
Adult 18 years
200 – 239 mg/dL
5.18 – 6.19 mmol/L
240 – 300 mg/dL
6.20 – 7.77 mmol/L
> 300 mg/dL
> 7.77 mmol/L
NA
Pediatric < 18 years
170 – 199 mg/dL
4.40 – 5.15 mmol/L
200 – 300 mg/dL
5.16 – 7.77 mmol/L
> 300 mg/dL
> 7.77 mmol/L
NA
Creatine Kinase
3.0 – 5.9 x ULN†
6.0 – 9.9 x ULN†
10.0 – 19.9 x ULN†
20.0 x ULN†
Creatinine
1.1 – 1.3 x ULN†
1.4 – 1.8 x ULN†
1.9 – 3.4 x ULN†
3.5 x ULN†
Glucose, serum, high
Nonfasting
116 – 160 mg/dL
6.44 – 8.88 mmol/L
161 – 250 mg/dL
8.89 – 13.88 mmol/L
251 – 500 mg/dL
13.89 – 27.75 mmol/L
> 500 mg/dL
> 27.75 mmol/L
Fasting
110 – 125 mg/dL
6.11 – 6.94 mmol/L
126 – 250 mg/dL
6.95 – 13.88 mmol/L
251 – 500 mg/dL
13.89 – 27.75 mmol/L
> 500 mg/dL
> 27.75 mmol/L
Glucose, serum, low
Adult and Pediatric 1 month
55 – 64 mg/dL
3.05 – 3.55 mmol/L
40 – 54 mg/dL
2.22 – 3.06 mmol/L
30 – 39 mg/dL
1.67 – 2.23 mmol/L
< 30 mg/dL
< 1.67 mmol/L
Infant*†, < 1 month
50 – 54 mg/dL
2.78 – 3.00 mmol/L
40 – 49 mg/dL
2.22 – 2.77 mmol/L
30 – 39 mg/dL
1.67 – 2.21 mmol/L
< 30 mg/dL
< 1.67 mmol/L
Lactate
ULN - < 2.0 x ULN without 
acidosis
2.0 x ULN without
acidosis
Increased lactate with pH < 7.3 without life-
threatening consequences
Increased lactate with pH <7.3 with life-
threatening consequences
LDL cholesterol (fasting)
Adult 18 years
130 – 159 mg/dL
3.37 – 4.12 mmol/L
160 – 190 mg/dL
4.13 – 4.90 mmol/L
190 mg/dL
4.91 mmol/L
NA
Pediatric > 2 - < 18 years
110 – 129 mg/dL
2.85 – 3.34 mmol/L
130 – 189 mg/dL
3.35 – 4.90 mmol/L
190 mg/dL
4.91 mmol/L
NA
Lipase
1.1 – 1.5 x ULN
1.6 – 3.0 x ULN
3.1 – 5.0 x ULN
> 5.0 x ULN


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Magnesium, serum, low
1.2 – 1.4 mEq/L
0.60 – 0.70 mmol/L
0.9 – 1.1 mEq/L
0.45 – 0.59 mmol/L
0.6 – 0.8 mEq/L
0.30 – 0.44 mmol/L
< 0.60 mEq/L
< 0.30 mmol/L
Pancreatic amylase
1.1 – 1.5 x ULN
1.6 – 2.0 x ULN
2.1 – 5.0 x ULN
> 5.0 x ULN
Phosphate, serum, low
Adult and Pediatric > 14 years
2.5 mg/dL – < LLN
0.81 mmol/L – < LLN
2.0 – 2.4 mg/dL
0.65 – 0.80 mmol/L
1.0 – 1.9 mg/dL
0.32 – 0.64 mmol/L
< 1.00 mg/dL
< 0.32 mmol/L
Pediatric 1 year – 14 years
3.0 – 3.5 mg/dL
0.97 – 1.13 mmol/L
2.5 – 2.9 mg/dL
0.81 – 0.96 mmol/L
1.5 – 2.4 mg/dL
0.48 – 0.80 mmol/L
< 1.50 mg/dL
< 0.48 mmol/L
Pediatric < 1 year
3.5 – 4.5 mg/dL
1.13 – 1.45 mmol/L
2.5 – 3.4 mg/dL
0.81 – 1.12 mmol/L
1.5 – 2.4 mg/dL
0.48 – 0.80 mmol/L
< 1.50 mg/dL
< 0.48 mmol/L
Potassium, serum, high
5.6 – 6.0 mEq/L
5.6 – 6.0 mmol/L
6.1 – 6.5 mEq/L
6.1 – 6.5 mmol/L
6.6 – 7.0 mEq/L
6.6 – 7.0 mmol/L
> 7.0 mEq/L
> 7.0 mmol/L
Potassium, serum, low
3.0 – 3.4 mEq/L
3.0 – 3.4 mmol/L
2.5 – 2.9 mEq/L
2.5 – 2.9 mmol/L
2.0 – 2.4 mEq/L
2.0 – 2.4 mmol/L
< 2.0 mEq/L
< 2.0 mmol/L
Sodium, serum, high
146 – 150 mEq/L
146 – 150 mmol/L
151 – 154 mEq/L
151 – 154 mmol/L
155 – 159 mEq/L
155 – 159 mmol/L
160 mEq/L
160 mmol/L
Sodium, serum, low
130 – 135 mEq/L
130 – 135 mmol/L
125 – 129 mEq/L
125 – 129 mmol/L
121 – 124 mEq/L
121 – 124 mmol/L
120 mEq/L
120 mmol/L
Triglycerides (fasting)
NA
500 – 750 mg/dL
5.65 – 8.48 mmol/L
751 – 1,200 mg/dL
8.49 – 13.56 mmol/L
> 1,200 mg/dL
> 13.56 mmol/L
Uric acid
7.5 – 10.0 mg/dL
0.45 – 0.59 mmol/L
10.1 – 12.0 mg/dL
0.60 – 0.71 mmol/L
12.1 – 15.0 mg/dL
0.72 – 0.89 mmol/L
> 15.0 mg/dL
> 0.89 mmol/L
URINALYSIS
Standard International Units are listed in italics
Hematuria (microscopic)
6 – 10 RBC/HPF
> 10 RBC/HPF
Gross, with or without clots OR with RBC 
casts
Transfusion indicated
Proteinuria, random
Collection
1 +
2 – 3 +
4 +
NA


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LABORATORY
PARAMETER
GRADE 1
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4
POTENTIALLY
LIFE-THREATENING
Proteinuria, 24 hour collection
Adult and Pediatric  10 years
200 – 999 mg/24 h
0.200 – 0.999 g/d
1,000 – 1,999 mg/24 h
1.000 – 1.999 g/d
2,000 – 3,500 mg/24 h
2.000 – 3.500 g/d
> 3,500 mg/24 h
> 3.500 g/d
Pediatric > 3 mo -< 10 years
201 – 499 mg/m2/24 h
0.201 – 0.499 g/d
500 – 799 mg/m2/24 h
0.500 – 0.799 g/d
800 – 1,000 mg/m2/24 h
0.800 – 1.000 g/d
> 1,000 mg/ m2/24 h
> 1.000 g/d
Values are for term infants.  Preterm infants should be assessed using local normal ranges.
† Use age and sex appropriate values (e.g., bilirubin).


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11.3.
Appendix 3: Pharmacogenetic Research
Pharmacogenetics – Background
Pharmacogenetics (PGx) is the study of variability in drug response due to hereditary 
factors in populations.  There is increasing evidence that an individual's genetic 
background (i.e., genotype) may impact the pharmacokinetics (absorption, distribution, 
metabolism, elimination), pharmacodynamics (relationship between concentrations and 
pharmacologic effects or the time course of pharmacologic effects) and/or clinical 
outcome (in terms of efficacy and/or safety and tolerability).  Some reported examples of 
PGx associations with safety/adverse events include:


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Drug
Disease
Gene Variant
Outcome
Abacavir
HIV 
[Hetherington, 
2002; Mallal, 
2002; 
Mallal, 2008]
HLA-B* 57:01 
(Human 
Leukocyte 
Antigen B)
Carriage of the HLA-B*57:01 variant has been 
shown to increase a patient's risk for 
experiencing hypersensitivity to abacavir.  
Prospective HLA-B*57:01 screening and 
exclusion of HLA-B*57:01 positive patients 
from abacavir treatment significantly 
decreased the incidence of abacavir 
hypersensitivity.  Treatment guidelines and 
abacavir product labeling in the United States 
and Europe now recommend (US) or require 
(EU) prospective HLA-B*57:01 screening prior 
to initiation of abacavir to reduce the incidence 
of abacavir hypersensitivity.  HLA-B*57:01
screening should supplement but must never 
replace clinical risk management strategies for 
abacavir hypersensitivity.
Carbamaze
pine
Seizure, Bipolar 
disorders & 
Analgesia Chung, 
2010; Ferrell, 
2008
HLA-B*15:02
Independent studies indicated that patients of 
East Asian ancestry who carry HLA-B*15:02
are at higher risk of Stevens-Johnson 
Syndrome and toxic epidermal necrolysis.  
Regulators, including the US FDA and the 
Taiwanese TFDA, have updated the 
carbamazepine drug label to indicate that 
patients with ancestry in genetically at risk 
populations should be screened for the 
presence of HLA-B*15:02 prior to initiating 
treatment with carbamazepine.
Irinotecan
Cancer 
[Innocenti, 2004; 
Liu, 2008; 
Schulz, 2009]
UGT1A1*28
Variations in the UGT1A1 gene can influence 
a patient’s ability to break down irinotecan, 
which can lead to increased blood levels of the 
drug and a higher risk of side effects. A dose 
of irinotecan that is safe for one patient with a 
particular UGT1A1 gene variation might be too 
high for another patient without this variation, 
raising the risk of certain side-effects that 
include neutropenia following initiation of 
Irinotecan treatment.  The irinotecan drug 
label indicates that individuals who have two 
copies of the UGT1A1*28 variant are at 
increased risk of neutropenia.  A genetic blood 
test is available that can detect variations in 
the gene.    
A key component to successful PGx research is the collection of samples during the 
conduct of clinical studies.


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Collection of whole blood samples, even when no a priori hypothesis has been identified, 
may enable PGx analysis to be conducted if at any time it appears that there is a potential 
unexpected or unexplained variation in response to DTG or any of the HIV medicines 
included in this study. 
Pharmacogenetic Research Objectives
The objective of the PGx research (if there is a potential unexpected or unexplained 
variation) is to investigate a relationship between genetic factors and response to DTG or 
any of the HIV medicines included in this study.  If at any time it appears there is 
potential variability in response in this clinical study or in a series of clinical studies with 
DTG, the following objectives may be investigated – the relationship between genetic 
variants and study treatment with respect to:

Relationship between genetic variants and the pharmacokinetics and/or 
pharmacodynamics of DTG or other medicines used in this study

Relationship between genetic variants and safety and/or tolerability of DTG or other 
medicines used in this study

Relationship between genetic variants and efficacy of DTG or other medicines used 
in this study
Study Population
Any subject who is enrolled in the clinical study, can participate in PGx research.  Any 
subject who has received an allogeneic bone marrow transplant must be excluded from 
the PGx research.
Subject participation in the PGx research is voluntary and refusal to participate will not 
indicate withdrawal from the clinical study or result in any penalty or loss of benefits to 
which the subject would otherwise be entitled.
Study Assessments and Procedures
Blood samples can be taken for Deoxyribonucleic acid (DNA) extraction and used in 
PGx assessments.
In addition to any blood samples taken for the clinical study, a whole blood sample (6 ml) 
will be collected for the PGx research using a tube containing EDTA.  It is recommended 
that the blood sample be taken at the first opportunity after a subject has been randomized 
and provided informed consent for PGx research, but may be taken at any time while the 
subject is participating in the clinical study.

The PGx sample is labelled (or “coded”) with a study specific number that can be 
traced or linked back to the subject by the investigator or site staff.  Coded samples 
do not carry personal identifiers (such as name or social security number).  The 
blood sample is taken on a single occasion unless a duplicate sample is required due 
to inability to utilize the original sample.  


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The DNA extracted from the blood sample may be subjected to sample quality control 
analysis.  This analysis will involve the genotyping of several genetic markers to confirm 
the integrity of individual samples.  If inconsistencies are noted in the analysis, then those 
samples may be destroyed.
The need to conduct PGx analysis may be identified after a study (or a set of studies) of 
DTG (or any of the HIV medicines included in this study) has been completed and the 
clinical study data reviewed.  In some cases, the samples may not be studied. e.g., no 
questions are raised about how people respond to DTG (or any of the HIV medicines 
included in this study).
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will use samples collected from the study for 
the purpose stated in this protocol and in the informed consent form.  
Subjects can request their sample to be destroyed at any time.
Subject Withdrawal from Study
If a subject who has consented to participate in PGx research withdraws from the clinical 
study for any reason other than being lost to follow-up, the subject will be given a choice 
of one of the following options concerning the PGx sample, if already collected:

Continue to participate in the PGx research with the PGx sample retained for 
analysis 

Withdraw from the PGx research and destroy the PGx sample 
If a subject withdraws consent for PGx research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in 
the site study records. The investigator should forward the Pharmacogenetic Sample 
Destruction Request Form to GSK as directed on the form. This can be done at any time 
when a subject wishes to withdraw from the PGx research or have their sample destroyed 
whether during the study or during the retention period following close of the main study.
Screen and Baseline Failures
If a blood sample for PGx research has been collected and it is determined that the 
subject does not meet the entry criteria for participation in the clinical study, then the 
investigator should instruct the participant that their PGx sample will be destroyed. No 
forms are required to complete this process as it will be completed as part of the consent 
and sample reconciliation process.  In this instance a sample destruction form will not be 
available to include in the site files.
Pharmacogenetics Analyses
1.
Specific genes may be studied that encode the drug targets, or drug mechanism of 
action pathways, drug metabolizing enzymes, drug transporters or which may 


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underpin adverse events, disease risk or drug response. These candidate genes may 
include a common set of ADME (Absorption, Distribution, Metabolism and 
Excretion) genes that are studied to determine the relationship between gene variants 
or treatment response and/or tolerance. 
In addition, continuing research may identify other enzymes, transporters, proteins or 
receptors that may be involved in response to DTG or any of the HIV medicines included 
in this study.  The genes that may code for these proteins may also be studied.
2.
Genome-wide scans involving a large number of polymorphic markers (e.g., single 
nucleotide polymorphisms) at defined locations in the genome, often correlated with 
a candidate gene, may be studied to determine the relationship between genetic 
variants and treatment response or tolerance. This approach is often employed when 
a definitive candidate gene(s) does not exist and/or the potential genetic effects are 
not well understood. 
If applicable and PGx research is conducted, appropriate statistical analysis methods will 
be used to evaluate pharmacogenetic data in the context of the other clinical data. Results 
of PGx investigations will be reported either as part of the main clinical study report or as 
a separate report. Endpoints of interest from all comparisons will be descriptively and/or 
graphically summarised as appropriate to the data.  A detailed description of the analysis 
to be performed will be documented in the study reporting and analysis plan (RAP) or in 
a separate pharmacogenetics RAP, as appropriate.  
Informed Consent
Subjects who do not wish to participate in the PGx research may still participate in the 
clinical study.  PGx informed consent must be obtained prior to any blood being taken for 
PGx research.
Provision of Study Results and Confidentiality of Subject’s PGx Data
GSK may summarize the PGx research results in the clinical study report, or separately, 
or may publish the results in scientific journals. 
GSK does not inform the investigator, subject, or anyone else (e.g., family members, 
study investigators, primary care physicians, insurers, or employers) of individual 
genotyping results that are not known to be relevant to the subject’s medical care at the 
time of the study, unless required by law. This is due to the fact that the information 
generated from PGx studies is generally preliminary in nature, and therefore the 
significance and scientific validity of the results are undetermined.


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References
Chung WH, Hung SL, Chen YT. Genetic predisposition of life-threatening antiepileptic-
induced skin reactions.  Expert Opin. Drug Saf. 2010; 9: 15-21.
Ferrell PB, McLeod HL.  Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson 
syndrome and toxic epidermal necrolysis: US FDA recommendations.  
Pharmacogenomics. 2008; 9: 1543-1546.
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, 
Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses 
AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. 
Lancet. 2002; 359:1121-1122.
Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch 
L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ.  Genetic variants in the UDP-
glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J 
Clin Oncol 2004; 22: 1382-1388.
Liu CY, Chen PM, Chiou TJ, Liu JH, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, 
Wang WS.  UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities 
without affecting treatment outcome and survival in patients with metastatic colorectal 
carcinoma.  Cancer. 2008; 112: 1932-1940.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte 
C, Maxwell D, James I.  Association between presence of HLA-B*5701, HLA-DR7, and 
HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir.  
Lancet. 2002; 359:727-732.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jägel-Guedes E, 
Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, 
Thorborn D, Benbow A; PREDICT-1 Study Team.  HLA-B*5701 screening for 
hypersensitivity to abacavir. N Engl J Med. 2008; 358; 568-579
Schulz C, Heinemann V, Schalhorn A, Moosmann N, Zwingers T, Boeck S, Giessen C, 
Stemmler HJ. UGT1A1 gene polymorphism: Impact on toxicity and efficacy of 
irinotecan-based regimens in metastatic colorectal cancer.  World J. Gastroenterol. 2009; 
15: 5058-5066.


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11.4.
Appendix 4: Liver Safety Drug Restart or Rechallenge 
Guidelines
VSLC GUIDELINES FOR DRUG RESTART OR RECHALLENGE AFTER
STOP FOR LIVER CRITERIA
1.
Drug rechallenge may be considered for a subject exhibiting compelling benefit for 
a critical medicine following drug-induced liver injury, if favorable benefit: risk and 
no alternative medicine available (Table 11, Figure 4)
2.
In Phase III, drug restart may be considered for liver events with a clear underlying 
cause (e.g. biliary, pancreatic events, hypotension, acute viral hepatitis), if not 
associated with drug-induced liver injury, alcoholic hepatitis or hypersensitivity, and 
drug not associated with HLA marker of liver injury, when liver chemistries improve 
to within 1.5x baseline and ALT<3xULN) (Table 12, Figure 5).
Background: Following drug-induced liver injury, drug rechallenge is associated with 
a 13% mortality across all drugs in prospective studies.  Clinical outcomes vary by 
drug, with nearly 50% fatality with halothane re-administered in one month of initial 
injury [Andrade, 2009].  However, some drugs seldom result in recurrent liver injury or 
fatality.
Risk factors for a fatal drug rechallenge outcome include:

hypersensitivity with initial liver injury (e.g. fever, rash, eosinophilia) [Andrade, 
2009]

jaundice or bilirubin2xULN with initial liver injury

prior serious adverse event or fatality has earlier been observed with drug 
rechallenge [Papay, 2009; Hunt, 2010]

evidence of drug-related preclinical liability (e.g. reactive metabolites; 
mitochondrial impairment [Hunt, 2010])
VSLC Decision Process for Drug Rechallenge Approval or 
Disapproval (Figure 4)

Principal Investigator (PI) requests consideration of drug rechallenge for a 
subject receiving compelling benefit from a critical or life-saving drug, who 
exhibits liver chemistry elevation meeting subject stopping criteria, with no 
alternative treatment

By definition treatment naïve subjects will only be considered for rechallenge if 
they were infected with a multi-resistant virus.

Medical Monitor and Global Clinical Safety and Pharmacovigilance (GCSP) 
Physician to review the subject’s rechallenge risk factors (consultation with the 
Hepatotoxicity Panel is available) and complete checklist (Table 11).


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
The Medical Monitor and GCSP Physician are accountable to review and agree
on:
–
compelling benefit of the investigational product (IP) for this subject and no 
alternative therapy
–
must present source data defining the patient’s current resistance profile 
with documented evidence of extensive drug resistance and previous drug 
history 
–
Relative benefit-risk of drug rechallenge, with consideration of the following 
high risk factors:
Initial liver injury event included: fever, rash, eosinophilia, or bilirubin 
2xULN (or direct bilirubin >35% of total, if available)
subject currently exhibits severe liver injury defined by: ALT 3xULN, 
bilirubin 2xULN (direct bilirubin >35% of total, if available), or INR1.5
SAE or fatality has earlier been observed with IP rechallenge
IP associated with known preclinical hepatic liability/ injury

Relevant physicians must review and agree on request for drug rechallenge:

Safety Team Leader, VP, or Senior Safety Physician

Medicines Development Leader and Project Physician Leader (GSK) or
Clinical Lead and Medical and Development Group Lead (Pfizer).

Request is taken to full VSLC for final decision 


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Figure 4
VSLC process for drug rechallenge approval or disapproval
The local operating company (LOC) medical director (ViiV and GSK where applicable) 
should be informed that study drug rechallenge is under consideration and of the final 
decision, whether or not to proceed.
Table 11
Checklist for drug rechallenge for critical medicine (Following drug-
induced liver injury, drug rechallenge is associated with 13% 
mortality across all drugs in prospective studies)
Yes
No
Compelling benefit of the investigational product (IP) for this subject and no 
alternative therapy.  Provide brief explanation:
Relative benefit-risk favorable for drug rechallenge, after considering the 
following high risk factors:

Initial liver injury event included: 
o
fever, rash, eosinophilia, or hypersensitivity
o
or bilirubin2xULN (direct bilirubin >35% of total)
o
Subject currently exhibits ALT 3xULN, bilirubin 2xULN 
(direct bilirubin >35% of total, if available), or INR1.5
o
SAE or fatality has earlier been observed with IP rechallenge
If yes, please provide brief explanation:
o
IP associated with known preclinical hepatic liability/ injury
o
Source data defining the patients current resistance profile
o
Previous drug history


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Drug Restart
Phase III “drug restart” can be approved by the VSLC for transient, defined non-drug-
induced liver injury if no evidence of:
•
immunoallergic injury /HLA association with injury
•
drug-induced liver injury (DILI)
•
alcoholic hepatitis
Study is drug held while labs and evaluation is completed to assess diagnosis.
VSLC Decision Process for Drug Restart Approval or Disapproval 
(Figure 5):

PI requests consideration of drug re-initiation for a subject stable or improving 
on IP, who exhibits liver chemistry elevation meeting subject stopping criteria, 
which is transient, non-drug-related, and liver chemistries improve to within 
1.5x baseline and ALT< 3xULN. 

GSK Medical Monitor and Clinical Safety Physician to review the subject’s 
diagnosis, restart risk factors and complete checklist (Table 12).
–
must present source data defining the patient’s current resistance profile 
with documented evidence of extensive drug resistance and previous drug 
history.

The LOC medical director (ViiV and GSK where applicable) should be 
informed that study drug restart is under consideration and of the final decision, 
whether or not to proceed.
Table 12
Checklist for Phase III drug restart after well-explained liver injury 
(e.g. biliary, pancreatic, hypotensive events, congestive heart 
failure, acute viral hepatitis), improving to liver chem1.5x baseline 
& ALT<3xULN
Yes
No
Is subject stable or improving on the investigational product (IP)?
Do not restart if the following risk factors at initial liver injury:

fever, rash, eosinophilia, or hypersensitivity 

drug-induced liver injury 

alcoholic hepatitis (AST>ALT, typically <10xULN)

IP has an HLA genetic marker associated with liver injury (e.g. 
lapatinib, abacavir, amoxicillin/clavulanate)
Source data defining the patients current resistance profile
Previous drug history


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
Relevant physicians must review and agree on request for drug restart:  

Safety Team Leader, VP, or Senior Safety Physician

Medicines Development Leader and Project Physician Leader (GSK) or 
Clinical Lead and Medical and Development Group Lead (Pfizer).

Hepatotoxicity Panel consultation is available.

Justification for drug restart outlining the benefit and risk for this subject must 
be recorded by GCSP Physician and sent to the VSLC Secretary.

VSLC must approve drug re-initiation and dosing regimen
Figure 5
VSLC process for drug restart approval or disapproval
1. Andrade, 2009; 2. Papay, 2009; 3. Hunt, 2010
Medical monitor, GCSP Physician and PI actions for Restart or 
Rechallenge following VSLC decision
Medical Monitor and (Global Clinical Safety and Pharmacovigilance) GCSP 
Physician Actions

Medical Monitor must notify PI of VSLC’s rechallenge (or restart) decision and 
recommended dosing regimen in writing and Medical Monitor must record note 
in study files.


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
The Safety Review Team must record rechallenge (or restart) outcomes and the 
GCSP Physician must send these to the VSLC

All severe reactions (rechallenge associated with bilirubin>2xULN or jaundice, 
or INR1.5), SAEs or fatalities with drug rechallenge (or restart) must be 
immediately reported to Line Management, VSLC Chair, VP Global Medical 
Strategy and EU Qualified Person for Pharmacovigilance. 
Principal Investigator Actions:

The PI must obtain Ethics Committee or Institutional Review Board approval of 
drug rechallenge or restart, as required. 

If drug re-initiation VSLC-approved, the patient must provide informed consent 
with a clear description of possible benefits and risks of drug administration 
including recurrent, more severe liver injury or possible death.
–
Targeted drug rechallenge or drug restart consent form must be used.

The patient’s informed consent must be recorded in the study chart, and the drug 
administered at agreed dose, as communicated by Medical Monitor.

Liver chemistries must be followed twice weekly for ‘rechallenge’ cases and 
once weekly for ‘restart’ cases for one month or for as long as clinically 
indicated following drug re-initiation.  If subject exhibits protocol-defined liver 
chemistry elevations, IP should be discontinued as protocol specified.
VSLC and the IRB/IEC must be informed of the patient’s outcome following drug 
rechallenge or restart.
Rechallenge/restart safety outcomes:

0 = no liver chemistry elevation

1 = recurrent liver chemistry elevation not meeting subject stopping criteria

2 = recurrent liver chemistry elevation meeting subject stopping criteria

3 = serious adverse event

4 = fatality
References:
Andrade RJ, Robles M, Lucena MI.  Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf. 2009;8:709-714.
Hunt, CM.  Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review.  Hepatol. 2010;52:2216-
2222. 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, Hunt CM.  Drug-induced liver 
injury following positive drug rechallenge.  Regul Tox Pharm. 2009;54:84-90. 


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11.5.
Appendix 5: Country Specific Requirements
United Kingdom
This requirement has been included based on requests from the Medicines and Healthcare 
products Regulatory Agency (MHRA) to include information on the specific duration of 
the Continuation Phase/Study Treatment for similar Phase III trials being conducted with 
dolutegravir.
Study Duration
In this study, the date of last study treatment administration in the UK will be determined 
by the completion of the 48 week randomized phase of the study for the last UK subject 
enrolled (it will not be determined by the completion of the Continuation Phase). The 
last subject will be enrolled by February 2015, and hence the last study treatment 
administration will occur by 28 February 2016.
(Note: The Continuation Phase is intended to provide subjects on DTG/ABC/3TC FDC 
with post-study access to DTG/ABC/3TC FDC until it becomes available in their 
countries. For subjects in the UK, the Continuation Phase is anticipated to conclude by 
31 March 2015, when DTG/ABC/3TC FDC is anticipated to become available).


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11.6.
Appendix 6: 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 sterilisation 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.
Reference
Hatcher RA, Trussell J, Nelson AL, et al, editors. Contraceptive Technology. 
20th edition. Atlanta, Georgia: Ardent Media, Inc., 2011: 50. Table 3-2. 


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11.7.
Appendix 7: Protocol Changes
11.7.1.
Protocol Amendment 01 (12-AUG-2013)
This protocol amendment applies to all participating sites.
Rationale for Protocol Amendment 01:
i. For clarification purposes, the Child-Pugh Classification has been removed as a method 
to determine the degree of hepatic impairment (Exclusion Criterion Number 5). Of 
note, there is no change to the intended study population as a result of this change (i.e. 
subjects with any degree of hepatic impairment are still excluded). The Child-Pugh 
Classification is intended to grade hepatic impairment in subjects already known to 
have hepatic impairment.  Application of this tool to subjects with no hepatic 
impairment will result in a score of at least 5 and a classification of ‘mild hepatic 
impairment’, therefore it is not a suitable screening tool for populations which include 
those with no hepatic impairment.  
ii. For clarification purposes, Figure 2, in Section 4.5.1. Virologic Criteria for Subject 
Management at Week 24, has been updated to differentiate between the two scenarios 
in which re-testing for HIV-1 RNA levels is required and to match central laboratory 
wording to be provided to sites when subjects meet virologic management criteria. Of 
note, the amendment does not result in any change in action for sites.
iii. Removal of the assessment for bone marker analytes during the Continuation Phase 
(every 12 weeks after Week 48):  This requirement was included in the Time and 
Events Schedule in error.  Subjects on the ATV+RTV+TDF/FTC arm will have 
completed the study at Week 48 and monitoring of bone marker analytes for subjects 
on the DTG/ABC/3TC arm beyond Week 48 is not considered necessary. Since this
assessment is not part of a primary or key safety endpoint, the removal of this 
assessment at this timepoint was previously documented in a Study File Note and is 
now included in this protocol amendment for completeness.
iv. Inclusion of a reference omitted in the original protocol [IAS USA, 2013].
v. For clarification purposes, corrections have been made to formatting issues and 
typographical errors and to maintain consistency in use of wording and terms between 
sections.

The term ‘virologic failure’ has been replaced with ‘confirmed virologic withdrawal 
criteria’ to maintain consistency with wording for virologic criteria for subject 
management in Section 4.5.1.
A list of specific changes is provided below. Unless stated otherwise, new text is 
represented in bold font, and deleted text in strikethrough font.


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Protocol Summary, Secondary Objectives, bullet 3
The following text has been revised:

To assess the development of viral resistance in subjects experiencing virologic 
failure who meet confirmed virologic withdrawal criteria;
Protocol Summary, Study Endpoints/Assessments, paragraph 5
The following text has been revised:
Virology endpoints will include the incidence of treatment emergent genotypic and 
phenotypic resistance in subjects experiencing virologic failure who meet confirmed 
virologic withdrawal criteria.
2. Objectives, Secondary Objectives, bullet 3
The following text has been revised:
To assess the development of viral resistance in subjects experiencing virologic failure 
who meet confirmed virologic withdrawal criteria
4.3. Exclusion Criteria
The following text has been revised:
5. Subjects with any degree of hepatic impairment, (Class A or greater) as determined 
by Child-Pugh classification (Section 11.2). For subjects requiring anticoagulation 
therapy, discussion with the study medical monitor will be required;
16. Any evidence of primary viral resistance based on the presence of any major 
resistance-associated mutation [IAS USA, 20123] in the Screening result or, if 
known, any historical resistance test result. Note: retests of Screening genotypes are 
not allowed;


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4.5.1. Virologic Criteria for Subject Management and Viral Resistance 
Testing, Figure 2. Virologic Criteria for Subject Management at 
Week 24
The following Figure has been revised:
Original Figure 2:
Week 24 
Visit
HIV-1 RNA is <50 c/mL
HIV-1 RNA is 50 c/mL
Maintain scheduled visit at Week 36
Perform an unscheduled visit in 
approximately 4-6 weeks to reassess plasma 
HIV-1 RNA
Subject has met “4 to 6 Week HIV-1 RNA 
Testing Criterion”
Proceed to Figure 3
Revised Figure 2:
Week 24 Visit
HIV-1 RNA is 
<50 c/mL
HIV-1 RNA is 50 c/mL 
but <400 c/mL
HIV-1 RNA is 400 c/mL
Maintain 
scheduled visit 
at Week 36
Perform an unscheduled visit in 
approximately 4-6 weeks to 
reassess plasma HIV-1 RNA
Subject has met “4 to 6 Week 
HIV-1 RNA Testing Criterion”
Proceed to Figure 3
Perform an unscheduled 
visit in approximately 4-6 
weeks to reassess plasma 
HIV-1 RNA
Subject has met 
“Suspected Virologic 
Withdrawal Criterion”
Proceed to Figure 3
5.1.2. Tablet Formulations of ATV, RTV, TDF/FTC FDC, paragraph 2
The following text has been revised:
Tenofovir disoproxil fumarate/ emtricitabine fixed dose combination (TDF/3TCFTC
FDC [Truvada])


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6.1. Time and Events Schedule, Table 3 Time and Events Table
The following text has been revised:
Child-Pugh Classification: Deletion of the row representing the ‘Child-Pugh 
Classification’.
Bone marker analytes:  Deletion of ‘X’ representing the assessment for bone marker 
analytes during the Continuation Phase.  
The following text (footnote) has been deleted:
x: Child-Pugh Score should be calculated using results from the Screening Visit.
6.6.1. Virology Endpoints

Incidence of treatment-emergent genotypic and phenotypic resistance in subjects
experiencing virologic failure who meet confirmed virologic withdrawal criteria.
10.
References
The title of the following reference was formatted incorrectly and is corrected below:
Hill, A, Sabin, C. Designing and interpreting noninferiority trials in naïve and 
experienced patients. AIDS. 2008;22(8):913-921.
The following text (reference) has been added:
International AIDS Society (IAS)–USA. Update of the Drug Resistant Mutations in 
HIV-1: March 2013. Topics in HIV Medicine 2013; 21(1): 6-14.
11.2 Appendix 2: Child-Pugh Classification
The following text has been deleted:
11.2 Appendix 2: Child-Pugh Classification
A subject is classified with mild hepatic impairment (Class A) if their overall sum of 
scores is 5-6 points, moderate hepatic impairment (Class B) if their overall sum of scores 
is 7-9 points, and severe hepatic impairment (Class C) if their overall sum of scores is 10-
15 based on the Child-Pugh system [Pugh, 1973] scoring described in the following table
(Table 11).  For subjects requiring anticoagulation therapy, discussion with the study 
medical monitor will be required.


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Table 11
Child-Pugh System
Finding 
Points Scored for Each Observed Finding 
1
2
3
Encephalopathy Grade1 
None
1 or 2
3 or 4
Ascites
Absent
Slight
Moderate
Serum bilirubin, SI units (μmol/L), 
Serum bilirubin, conventional units (mg/dL) 
<34
<2
34 to 52
2 to 3
>52
>3
Serum albumin, SI units (g/L) 
Serum albumin, conventional units (mg/dL) 
>35
>3.5
28 to 35
2.8 to 3.5
<28
<2.8
Prothrombin Time (seconds prolonged) or 
INR 
<4
<1.7
4 to 6
1.7 to 2.3
>6
>2.3
1. Grade 0: normal consciousness, personality, neurological examination, electroencephalogram
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles per second waves
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cycles per second delta activity
[Pugh,1973; Lucey, 1997]
Lucey MR, Brown KA, Everson GT, Fung JJ, Gish R, Keeffe EB, et al. Minimal Criteria
for Placement of Adults on the Liver Transplant Waiting List Liver Transplantation ans
Surgery, Vol. 3, No 6 (November), 1997:pp 628-637
Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the
oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 649-649.
Section, Appendix and Table numbers affected by deletion of the Child-Pugh 
Classification have been updated accordingly.
11.7.2.
Protocol changes for Amendment 02 (11-AUG-2014) from 
Amendment 01 (12-AUG-2013)
This protocol amendment applies to sites in the UK only.  The amendment was 
initially implemented as a ‘alternative’ format amendment, and was brought into 
the main protocol text at the time of Protocol Amendment 03.
Rationale for Protocol Amendment 02:
The UK Medicines and Healthcare products Regulatory Agency (MHRA) requested the 
following changes to the UK country specific information on study duration 
(Appendix 5): i) a specific end date for treatment for subjects in the UK, and ii) removal 
of the term ‘commercially available’ in reference to treatment ending when 
investigational product is ‘commercially available’.
The medical monitor information in the Sponsor Information Page has also been updated.


2 0 1 3 N 1 6 1 6 4 9 _ 0 3
C O N FI D E N TI A L
I N G 1 1 7 1 7 2
1 2 6
LI S T O F S P E CI FI C C H A N G E S :

S p o ns or I nf or m ati o n P a ge; Me dic al M o nit or C o nt act I nf or m ati o n a n d Seri o us 
A d verse E ve nts ( S A E) C o nt act I nf or m ati o n: 
Ori gi n al Ver b ati m Te xt
, M D
I nfecti o us Diseases T A U,
Gla x o S mit h Kli ne
5 M o ore Dri ve, N 2. 2 2 1 3
Researc h Tria n gle Par k, N C 2 7 7 0 9, U S A
Tele p h o ne: 
M o bile: 
Facsi mile: 
e-mail: 
A m e n de d Te xt
, M D
I nfecti o us Diseases T A U,
Gla x o S mit h Kli ne
5 M o ore Dri ve, 
Researc h Tria n gle Par k, N C 2 7 7 0 9, U S A
Tele p h o ne: 
M o bile: 
Facsi mile:
e-mail:

A p pe n di x 5: C o u ntr y S pecific Re q uire me nts
Ori gi n al Ver b ati m Te xt
U nit e d Ki n g d o m
T his re q uire me nt has bee n i ncl u de d base d o n re q uests fr o m t he Me dici nes a n d Healt hcare 
pr o d ucts Re g ulat or y  A ge nc y ( M H R A) t o i ncl u de i nf or mati o n o n t he s pecific d urati o n of 
t he O pe n- La bel/ C o nti n uati o n P hase f or si milar P hase III trials bei n g c o n d ucte d wit h 
d ol ute gra vir.
St u d y D ur ati o n
T he C o nti n uati o n P hase is i nte n de d t o pr o vi de access t o D T G/ A B C/ 3 T C F D C u ntil 
D T G/ A B C/ 3 T C F D C recei ves l ocal ( by c o u ntr y) Re g ulat or y a p pr o val a n d bec o mes 
c o m merciall y a vaila ble. T heref ore, t he d urati o n of t he C o nti n uati o n P hase will var y  fr o m 
c o u ntr y t o c o u ntr y a n d is de pe n de nt o n t he recr uit me nt ti me f or t he st u d y a n d t he ti me 
ta ke n t o ac hie ve l ocal a p pr o val f or mar keti n g. F or s u bjects i n t he U K, esti mati n g a n 1 8 
m o nt h recr uit me nt peri o d, Mar keti n g A p plicati o n A ut h orisati o n ( M A A) s u b missi o n i n 
2 0 1 3, a n d all o wi n g f or re g ulat or y  re vie w ti me of t he M A A, t he C o nti n uati o n P hase is 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


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anticipated to conclude in the UK in approximately 1Q2015, and subjects who complete 
the randomized phase of the study after this date are expected transition directly to 
commercial supplies.
Amended Text
United Kingdom
This requirement has been included based on requests from the Medicines and Healthcare 
products Regulatory Agency (MHRA) to include information on the specific duration of 
the Continuation Phase/Study Treatment for similar Phase III trials being conducted with 
dolutegravir.
Study Duration
In this study, the date of last study treatment administration in the UK will be determined 
by the completion of the 48 week randomized phase of the study for the last UK subject 
enrolled (it will not be determined by the completion of the Continuation Phase). The 
last subject will be enrolled by February 2015, and hence the last study treatment 
administration will occur by 28 February 2016.
(Note: The Continuation Phase is intended to provide subjects on DTG/ABC/3TC FDC 
with post-study access to DTG/ABC/3TC FDC until it becomes available in their 
countries. For subjects in the UK, the Continuation Phase is anticipated to conclude by 
31 March 2015, when DTG/ABC/3TC FDC is anticipated to become available).
11.7.3.
Protocol changes for Amendment 03 (19-JUN-2018) from 
Amendment 02 (11-AUG-2014)
This protocol amendment applies to all participating sites.
Rationale for Protocol Amendment 03:
Changes were made to the protocol to manage and mitigate risks following identification 
of a potential safety issue related to neural tube defect in infants born to women with 
exposure to dolutegravir at the time of conception.

The Risk Assessment table (Section 1.3.1.) was updated to include language 
regarding risk and mitigation of neural tube defects.

Inclusion criterion #2 (Section 4.2.) was updated to exclude the double barrier method 
of contraception, and refer to the Modified List of Highly Effective Methods for 
Avoiding Pregnancy in Females of Reproductive Potential.

The withdrawal criteria (Section 4.5.) were updated to include a reminder that 
females of reproductive potential who change their minds and desire to be pregnant, 
or who state they no longer are willing to comply with the approved pregnancy 
avoidance methods, should also be withdrawn from the study.


2 0 1 3 N 1 6 1 6 4 9 _ 0 3
C O N FI D E N TI A L
I N G 1 1 7 1 7 2
1 2 8

T he Ti me a n d E ve nts ta ble ( Secti o n 6. 1. ) was u p date d t o i ncl u de a re mi n der f or 
i n vesti gat ors t o c hec k at e ver y visit t hat fe males of re pr o d ucti ve p ote ntial are 
a v oi di n g pre g na nc y.

A p pe n di x 6 was a d de d: M o difie d L ist of Hi g hly Effecti ve Met h o ds f or A v oi di n g 
Pre g na nc y  i n Fe males of Re pr o d ucti ve P ote ntial
A d mi nistrati ve u p dates were ma de
LI S T O F S P E CI FI C C H A N G E S
U nless st ate d ot her wise, ne w te xt is re prese nte d i n b ol d f o nt, a n d delete d te xt i n 
stri ket hr o u g h f o nt.

A ut h ors
 

S p o ns or I nf or m ati o n P a ge; Me dic al M o nit or C o nt act I nf or m a ti o n a n d Seri o us 
A d verse E ve nts ( S A E) C o nt act I nf or m ati o n: 
, M D
I nfecti o us Diseases T A U,
Gla x o S mit h Kli ne
5 M o ore Dri ve, N 2. 2 2 1 3
Researc h Tria n gle Par k, N C 2 7 7 0 9, U S A
Tele p h o ne: 
M o bile: 
Facsi mile: 
e-mail: 
, M D
Vii V Healt hcare,
5 M o ore Dri ve, 
Researc h Tria n gle Par k, N C 2 7 7 0 9, U S A
M o bile: 
Facsi mile: 
e-mail:

A b bre vi ati o ns
F R P
Fe m ales of Re pr o d ucti ve P ote nti al
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


2013N161649_03
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
Section 1.3.1. Risk Assessment
Potential Risk of 
Clinical 
Significance
Data/Rationale for Risk
Mitigation Strategy1
Investigational Product (IP) [DTG/ABC/3TC] 
Refer to IB for additional information on DTG and DTG/ABC/3TC
Refer to approved country product label for additional information on ABC/3TC
DTG: Neural tube 
defects
In one ongoing birth outcome surveillance 
study in Botswana, early results from an 
unplanned interim analysis show that 
4/426 (0.9%) of women who were taking 
DTG when they became pregnant had 
babies with neural tube defects compared 
to a background rate of 0.1%.
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 6, Section
11.6), until at least 2 weeks after 
discontinuation of IP
2. Women who are breastfeeding or 
plan to become pregnant or
breastfeed during the study are 
excluded;
3. Women who become pregnant, or 
who desire to be pregnant while in 
the study, or who state they no 
longer are willing to comply with 
the approved pregnancy avoidance 
methods, will have study treatment 
discontinued and withdrawn from 
the study.
4. Females of reproductive potential 
are reminded re: pregnancy 
avoidance and adherence to 
contraception requirements at 
every study visit.
5. Pregnancy status is monitored at 
every study visit

Section 4.2. Inclusion Criteria
2. A female, may be eligible to enter and participate in the study if she: 
a.
is of non-child-bearing potential either defined as post-menopausal (12 months of 
spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of 
becoming pregnant with documented tubal ligation, hysterectomy or bilateral 
oophorectomy or, 
b. is of child-bearing potential with a negative pregnancy test at both Screening and 
Day 1 and agrees to use one of the following methods of contraception to avoid 
pregnancy:


2013N161649_03
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130

Refer to Appendix 6, Section 11.6: Modified List of Highly Effective 
Methods for Avoiding Pregnancy in Females of Reproductive Potential. 

Complete abstinence from intercourse from 2 weeks prior to administration 
of IP, throughout the study, and for at least 2 weeks after discontinuation of 
all study medications;

Double barrier method (male condom/spermicide, male condom/diaphragm, 
diaphragm/spermicide);

Any intrauterine device (IUD) with published data showing that the expected 
failure rate is <1% per year (not all IUDs meet this criterion, see the SPM for 
an example listing of approved IUDs);

Male partner sterilization prior to the female subject’s entry into the study 
and this male is the sole partner for that subject;

Any other method with published data showing that the expected failure rate 
is <1% per year.

Approved hormonal contraception for subjects randomized to the 
DTG/ABC/3TC arm (see the SPM for a listing of examples of approved 
hormonal contraception).

Approved hormonal contraception and a barrier method for subjects 
randomized to the ATV+RTV+TDF/FTC arm.  
Any contraception method must be used consistently, in accordance with the approved 
product label and for at least 2 weeks after discontinuation of IP.  The investigator is 
responsible for ensuring that subjects understand how to properly use these 
methods of contraception.

Section 4.5. Withdrawal Criteria
Subjects must be prematurely discontinued from the study for any of the following 
reasons:

Pregnancy (intrauterine), regardless of termination status of pregnancy.  As a 
reminder, females of reproductive potential who changed their minds and 
desire to be pregnant, or who state they no longer are willing to comply with the 
approved pregnancy avoidance methods, should also be withdrawn from the 
study.

Section 6.1. Time and Events Schedule
h.  Pregnancy testing. Women of childbearing potential only. S=serum, U=urine. Remind females of 
reproductive potential of the need to avoid pregnancy while in study and adherence to the 
study’s contraception requirements.

Section 10. References
GlaxoSmithKline Document Number 2017N352880_00: GSK1349572 Clinical 
Investigator's Brochure, Version 11, Supplement 01, December 2017.


2013N161649_03
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GlaxoSmithKline Document Number 2017N352880_01: GSK1349572 Clinical 
Investigator's Brochure, Version 11, Supplement 02, June 2018.
GlaxoSmithKline Document Number RM2007/00683/0611: GSK1349572 Clinical 
Investigator's Brochure. February 2013. Version 11, October 2017.
References to the DTG IB were also updated throughout the protocol to reference the 
current DTG IB.

Section 11.6, Appendix 6
A new Section 11.6, Appendix 6 was inserted; the previous Appendix 6 (Section 11.6, 
Appendix 6 Protocol Changes) was updated to Section 11.7, Appendix 7.
Appendix 6: 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 sterilisation 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.
Reference
Hatcher RA, Trussell J, Nelson AL, et al, editors. Contraceptive Technology. 
20th edition. Atlanta, Georgia: Ardent Media, Inc., 2011: 50. Table 3-2. 

SAP_001.pdf: 
Reporting and Analysis Plan 
 
 
 
Study ID: 117172 
 
Official Title of Study: Reporting and Analysis Plan for ING117172 A Phase IIIb, 
randomized, open-label study of the safety and efficacy of dolutegravir/abacavir/lamivudine 
once daily compared to atazanavir and ritonavir plus tenofovir/emtricitabine once daily in HIV-
1 infected antiretroviral therapy naïve women 
 
US IND: 114,820 
 
EudraCT: 2012-005823-34 
 
Date of Document: 19-Aug-2022  
 
 
 
 
 


 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
ING117172 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for ING117172 A Phase IIIb, 
randomized, open-label study of the safety and efficacy of 
dolutegravir/abacavir/lamivudine once daily compared to 
atazanavir and ritonavir plus tenofovir/emtricitabine once 
daily in HIV-1 infected antiretroviral therapy naïve women 
Compound Number  
: GSK1349572+GR109714+GI265235 (GSK2619619) 
Effective Date  
: Refer to the document date 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Reports for Protocol ING117172. 
• 
This RAP is intended to describe all the planned analyses required for the study.  
• 
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverables. 
• 
The purpose of RAP Amendment 01 (to the originally approved RAP dated 20- 
       OCT-2015) is to provide details on the Final (End of Study) analysis. 
 
 
Author’s Name and Functional Area:  
Author 
Date 
Lead 
 
 
01-Aug-2022 
Associate Statistician, Biostatistics 
 
 
 
 
PPD


 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
ING117172 
 
2 
 
RAP Team Reviews: 
RAP Team Review Confirmations (Vault TMF):  
Reviewer  
Date 
 
Principal Programmer/ Analyst, Biostatistics, GSK 
19-Aug-2022 
 
Clinical Science Lead, ViiV 
19-Aug-2022 
 
Safety Lead, GSK 
19-Aug-2022 
 
Clinical Development Leader, ViiV 
19-Aug-2022 
 
Clinical Development Manager, ViiV 
19-Aug-2022 
 
Study Delivery Lead, GSK 
19-Aug-2022 
 
 
Approval (Vault TMF): 
Approver 
 
Manager, Statistics  
 
 
 
 
 
 
 
Copyright 2022 ViiV Healthcare and the GlaxoSmithKline group of companies. All 
rights reserved.  Unauthorised copying or use of this information is prohibited. 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
ING117172 
 
3 
 
The main changes included in RAP Amendment 01 are: 
Addition of Appendix 13 (Section 12.13) to provide additional details of the planned 
analyses and data displays for ING117172 Final/End of Study (EoS) reporting. 
Appendix 14 (List of data displays) updated to reflect the updates to the EoS analyses in 
Appendix 13. 
 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
4 
 
TABLE OF CONTENTS 
PAGE 
1. 
CHRONOLOGY ....................................................................................................... 6 
2. 
REPORTING & ANALYSIS PLAN SYNPOSIS ......................................................... 6 
3. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 8 
3.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 8 
3.2. 
Study Objective(s) and Endpoint(s)............................................................... 8 
3.3. 
Study Design ................................................................................................ 9 
3.4. 
Statistical Hypotheses................................................................................. 10 
4. 
PLANNED ANALYSES .......................................................................................... 10 
4.1. 
Interim Analyses ......................................................................................... 10 
4.2. 
Final Analyses ............................................................................................ 10 
5. 
ANALYSIS POPULATIONS ................................................................................... 11 
5.1. 
Protocol Deviations ..................................................................................... 12 
6. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 12 
7. 
STUDY POPULATION ANALYSES ....................................................................... 14 
7.1. 
Overview of Planned Analyses ................................................................... 14 
8. 
PRIMARY STATISTICAL ANALYSES .................................................................... 15 
8.1. 
Efficacy Analyses ........................................................................................ 15 
8.1.1. 
Overview of Planned Efficacy Analyses ....................................... 16 
8.1.2. 
Planned Efficacy Statistical Analyses ........................................... 17 
9. 
SECONDARY STATISTICAL ANALYSES ............................................................. 20 
9.1. 
Efficacy Analyses ........................................................................................ 20 
9.1.1. 
Overview of Planned Efficacy Analyses ....................................... 20 
9.2. 
Safety Analyses .......................................................................................... 21 
9.2.1. 
Overview of Planned Analyses .................................................... 21 
9.2.2. 
Planned Safety Statistical Analyses ............................................. 24 
10. OTHER STATISTICAL ANALYSES ....................................................................... 26 
10.1. 
Health Outcomes ........................................................................................ 26 
10.2. 
Virology ...................................................................................................... 27 
11. REFERENCES ....................................................................................................... 28 
12. APPENDICES ........................................................................................................ 29 
12.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 30 
12.1.1. 
Exclusions from Per Protocol Population ..................................... 30 
12.2. 
Appendix 2: Time & Events ......................................................................... 31 
12.2.1. 
Protocol Defined Time & Events .................................................. 31 
12.3. 
Appendix 3: Assessment Windows ............................................................. 33 
12.3.1. 
Definitions of Assessment Windows for Analyses ........................ 34 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
5 
 
12.4. 
Appendix 4: Treatment States & Phases .................................................... 34 
12.4.1. 
Treatment Phases ....................................................................... 34 
12.4.2. 
Treatment States ......................................................................... 34 
12.4.3. 
Treatment Phases and States ...................................................... 37 
12.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 38 
12.5.1. 
Study Treatment & Sub-group Display Descriptors ...................... 38 
12.5.2. 
Baseline Definition & Derivations ................................................. 38 
12.5.3. 
Reporting Process & Standards ................................................... 38 
12.6. 
Appendix 6: Derived and Transformed Data ............................................... 40 
12.6.1. 
General ........................................................................................ 40 
12.6.2. 
Study Population .......................................................................... 41 
12.6.3. 
Safety .......................................................................................... 43 
12.6.4. 
Efficacy ........................................................................................ 45 
12.6.5. 
Viral Genotyping and Phenotyping ............................................... 47 
12.6.6. 
Health outcomes .......................................................................... 49 
12.7. 
Appendix 7: Premature Withdrawals & Handling of Missing Data ............... 51 
12.7.1. 
Premature Withdrawals ................................................................ 51 
12.7.2. 
Handling of Missing Data ............................................................. 51 
12.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 53 
12.9. 
Appendix 9: Examination of Covariates and Subgroups .............................. 53 
12.9.1. 
Handling of Covariates, Subgroups & Other Strata ...................... 53 
12.10. Appendix 10: Model Checking and Diagnostics for Statistical 
Analyses ..................................................................................................... 55 
12.10.1. Statistical Analysis Assumptions .................................................. 55 
12.11. Appendix 11: Snapshot ............................................................................... 56 
12.12. Appendix 12: Abbreviations & Trade Marks ................................................ 59 
12.12.1. Abbreviations ............................................................................... 59 
12.12.2. Trademarks ................................................................................. 61 
12.13. Appendix 13: Final (End of Study) Analysis ................................................ 61 
12.13.1. Study Phases .............................................................................. 62 
12.13.2. Analysis Populations for the Continuation Phase ......................... 63 
12.13.3. Study Population .......................................................................... 64 
12.13.4. Safety Analysis ............................................................................ 64 
12.13.5. Efficacy Analysis .......................................................................... 65 
12.13.6. Virology Analysis ......................................................................... 65 
12.13.7. COVID-19 Analysis ...................................................................... 70 
12.13.8. List of Data Displays for Final (End of Study) ............................... 70 
12.14. Appendix 14: List of Data Displays.............................................................. 83 
12.14.1. Data Display Numbering .............................................................. 83 
12.14.2. Mock Example Shell Referencing ................................................ 83 
12.14.3. Deliverable ................................................................................... 84 
12.14.4. Study Population Tables .............................................................. 85 
12.14.5. Efficacy Tables ............................................................................ 88 
12.14.6. Efficacy Figures ........................................................................... 90 
12.14.7. Safety Figures ............................................................................. 91 
12.14.8. Health Outcomes Tables ............................................................. 92 
12.14.9. Virology Tables ............................................................................ 93 
12.14.10. Safety Tables ............................................................................... 94 
12.14.11. ICH Listings ............................................................................... 100 
12.14.12. Non-ICH Listings ........................................................................ 102 
12.15. Appendix 15: Example Mock Shells for Data Displays .............................. 107 
 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
6 
 
1. 
CHRONOLOGY 
Main RAP  
21-OCT-2015 
SF_1 00 Reporting and Analysis Plan 
(RAP)_ARIA_21Oct2015_v1 (Week 48 Interim Analysis) 
Amendment 1   
DD-MMM-YYYY  Appendix 13 added to provide details of the Analysis Plan 
for the Final (End of Study) Analysis. 
 
2. 
REPORTING & ANALYSIS PLAN SYNPOSIS 
Overview 
Key Elements of the RAP 
Purpose 
• 
This RAP describes all the planned analyses and outputs required for the 
Clinical Study Report(s) for Protocol ING117172. 
Protocol 
• 
This RAP is based on protocol amendment 03 [Dated: 19/JUN/2018 of study 
ING117172 (GSK Document No.:2013N161649_01) and eCRF Version 9.0. 
Primary 
Objective  
• 
To demonstrate the non-inferior antiviral activity of DTG/ABC/3TC FDC once 
daily compared to ATV+RTV+TDF/FTC FDC each administered once daily over 
48 weeks in HIV-1 infected ART naïve women. 
Primary 
Endpoint 
• 
The proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48 
using the Snapshot algorithm (Missing, Switch or Discontinuation = Failure) for 
the ITT-E population.  
Study 
Design 
• 
A 48 week Phase IIIb randomized, open-label, active-controlled, multicenter, 
parallel group, non-inferiority study. 
• 
The study will be conducted in approximately 474 HIV-1 infected ART-naïve 
women.  
• 
Subjects will be randomized 1:1 to receive a FDC of DTG 50mg/ ABC 600mg/ 
3TC 300mg once daily or ATV 300mg plus RTV 100mg and TDF 300mg/ FTC 
200mg FDC each administered once daily.  
• 
Randomization will be stratified by Screening plasma HIV-1 RNA (≤100,000 
copies/mL [c/mL] or >100,000 c/mL) and CD4+ cell count (≤350 cells/mm3 or 
>350 cells/mm3).  
• 
The study will comprise a Screening Phase (approximately 14-28 days), a 
Randomized Phase (48 weeks), and a Continuation Phase.  
• 
No dose reductions, modifications in dosage, or changes in the frequency of 
dosing of any components of each regimen will be allowed in this study. 
Planned 
Analyses 
• 
The main analysis will be conducted to evaluate the primary objective of the 
protocol when all subjects have completed their Week 48 visit. A final analysis 
will be conducted when all subjects have completed the study. Further data cuts 
and analyses may be conducted as necessary in order to support regulatory 
submissions and publications and pricing reimbursement dossiers. 
Analysis 
Populations 
• 
The Intent-to-Treat Exposed (ITT-E) Population will be used for summaries of 
efficacy and study population. The Safety Population will be used for 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
7 
 
Overview 
Key Elements of the RAP 
summaries of safety.  
• 
A ‘Per-Protocol’ Population and an Intent-to-Treat Population will be used to 
evaluate efficacy in sensitivity analyses. 
• 
Separate populations for virology analyses will also be defined. 
Hypothesis 
• 
This study is designed to show that the antiviral effect of the DTG/ABC/3TC 
FDC administered once daily is non-inferior to once daily ATV+RTV+TDF/FTC 
FDC. Non-inferiority can be concluded if the lower bound of a two-sided 95% 
confidence interval for the difference in response rates between the two 
treatment arms is greater than -12%. 
Primary 
Analyses 
• 
The primary endpoint will be analyzed using a Cochran-Mantel-Haenszel 
stratified analysis, adjusting from baseline stratification factors.  A point 
estimate and corresponding 95% confidence interval will be constructed for the 
adjusted difference in response rates between DTG and ATV treatment groups. 
• 
The primary analysis will be based on the ITT-E population using the Snapshot 
dataset. The primary comparison will be made at a one-sided 2.5% level of 
significance.   
Secondary 
Analyses 
• 
Proportion of subjects with plasma HIV-1 RNA <50 and <400 c/mL over time 
• 
Absolute values and changes from baseline in plasma HIV-1 RNA over time 
• 
Absolute values and changes from baseline in CD4+ cell counts over time 
• 
Incidence of HIV-1 disease progression 
• 
Safety data will be presented in tabular format and summarized descriptively 
according to GSK’s Integrated Data Standards Library (IDSL) standards.  
• 
Change from baseline in fasting lipids. 
 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
8 
 
3. 
SUMMARY OF KEY PROTOCOL INFORMATION 
3.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in protocol amendment 1 (Dated: 12/AUG/2013). 
3.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To demonstrate the non-inferior 
antiviral activity of DTG/ABC/3TC 
FDC once daily compared to 
ATV+RTV+TDF/FTC FDC each 
administered once daily over 48 
weeks in HIV-1 infected ART naïve 
women. 
• 
The primary endpoint for this study will be the proportion 
of subjects with plasma HIV-1 RNA <50 copies/mL at 
Week 48 using the Snapshot algorithm (Missing, Switch 
or Discontinuation = Failure) for the ITT-E population 
Secondary Objectives 
Secondary Endpoints 
• 
To evaluate the antiviral and 
immunological activity and incidence 
of disease progression (HIV-
associated conditions, AIDS and 
death) of DTG/ABC/3TC FDC once 
daily compared to 
ATV+RTV+TDF/FTC FDC once daily 
over time; 
• 
Proportion of subjects with plasma HIV-1 RNA <50 and 
<400 c/mL over time; 
• 
Absolute values and change from Baseline in plasma 
HIV-1 RNA over time; 
• 
Absolute values and changes from Baseline in CD4+ cell 
counts over time; 
• 
Incidence of disease progression (HIV-associated 
conditions, AIDS and death). 
• 
To compare the safety, tolerability, 
and laboratory parameters of 
DTG/ABC/3TC FDC once daily to 
ATV+RTV+TDF/FTC FDC once daily 
over time; 
• 
Incidence and severity of AEs and laboratory 
abnormalities; 
• 
Absolute values and changes over time in laboratory 
parameters; 
• 
Proportion of subjects who discontinue treatment due to 
AEs; 
• 
Change from Baseline in fasting lipids and glucose; 
• 
To assess the development of viral 
resistance in subjects who meet 
confirmed virologic withdrawal criteria; 
• 
Incidence of treatment-emergent genotypic and 
phenotypic resistance in subjects who meet confirmed 
virologic withdrawal criteria. 
• 
To evaluate renal markers (in urine 
and blood), and bone markers (in 
blood) in subjects treated with 
DTG/ABC/3TC FDC compared to 
ATV+RTV+TDF/FTC FDC; 
• 
Changes from Baseline in renal and bone markers. 
• 
To assess treatment satisfaction, and 
change in health-related quality-of-life 
for subjects treated with 
DTG/ABC/3TC FDC compared to 
ATV+RTV+TDF/FTC FDC; 
• 
Change from Baseline in health related quality of life 
using SF-12 at Week 48. 
• 
Treatment satisfaction for subjects treated with 
DTG/ABC/3TC FDC once daily and those treated with 
ATV+RTV+TDF/FTC FDC once daily at weeks 4, 12, 24, 
and 48 (or withdrawal from the study). 


 
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Objectives 
Endpoints 
• 
To evaluate the effect of patient 
characteristics (i.e., demographic 
factors, HIV-1 subtype, Baseline CD4) 
on response to DTG/ABC/3TC FDC 
compared to 
ATV+RTV+TDF/FTC FDC over time. 
• 
Proportion of subjects with plasma HIV-1 RNA <50 c/mL 
over time by subgroups.   
3.3. 
Study Design 
Overview of Study Design and Key Features 
Design Features 
• 48 week Phase IIIb randomized, open-label, active-controlled, 
multicenter, parallel group, non-inferiority study. The study comprises 
a Screening Phase (approximately 14-28 days), a Randomized 
Phase (48 weeks), and a Continuation Phase. 
Dosing 
• Randomized Phase: DTG/ABC/3TC FDC 50mg/600mg/300mg once 
daily or ATV (300mg) +RTV (100mg) +TDF/FTC FDC 
(300mg/200mg) all administered once daily, up to Week 48. 
• Continuation Phase: Only subjects randomized to the DTG/ABD/3TC 
FDC arm can continue past Week 48 in an open-label continuation 
phase.  
Treatment 
Assignment 
• N=474 randomized 1:1 across two treatment arms.  
• Randomization stratified by Screening plasma HIV-1 RNA (≤100,000 
copies/mL [c/mL] or >100,000 c/mL) and CD4+ cell count (≤350 
cells/mm3 or >350 cells/mm3).  
• GSK RandAll NG used to generate randomisation schedules. 
• Centralised randomization using GSK RAMOS for treatment 
allocation. 
Interim Analysis 
• The main analysis will be conducted to evaluate the primary objective 
of the protocol when all subjects have completed their Week 48 visit. 
Further data cuts and analyses may be conducted as necessary in 
order to support regulatory submissions and publications. 


 
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3.4. 
Statistical Hypotheses 
This study is designed to show that the antiviral effect of the DTG/ABC/3TC FDC 
administered once daily is non-inferior to once daily ATV+RTV+TDF/FTC FDC. 
Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence 
interval for the difference in response rates between the two treatment arms is greater 
than -12%. If rd is the response rate on DTG/ABC/3TC FDC and ra is the response rate on 
ATV+RTV+TDF/FTC FDC then the hypotheses can be written as follows: 
H0: rd – ra ≤ -12%  
H1: rd – ra > -12%. 
4. 
PLANNED ANALYSES 
4.1. 
Interim Analyses 
The main analysis will be conducted to evaluate the primary objective of the protocol 
when all subjects have completed their Week 48 visit. Further data cuts and analyses may 
be conducted as necessary in order to support regulatory submissions and publications. 
The planned primary analyses will be performed after the completion of the following 
sequential steps: 
1. All subjects have completed the Week 48 visit as defined in the protocol. 
2. All required database cleaning activities have been completed and final database 
release and database freeze has been declared by Data Management. 
3. All criteria for unblinding the randomisation codes have been met.  
4. Randomisation codes have been distributed according to RandAll NG procedures. 
4.2. 
Final Analyses 
A final End-of-Study analysis will be conducted when all subjects have completed the 
study. 
Details of which outputs will be produced at Week 48 and End of Study can be found in 
Section 12.14. 


 
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5. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
All Subjects 
Screened 
• Comprised of all subjects screened for 
inclusion in the study.  
• Subjects may be re-screened once, for which 
they will receive a new subject number.  
• Only the latest re-screening data will be 
included in the screening population 
summaries/analyses but all screening data will 
be listed. 
• Study Population 
Safety 
• Comprise of all subjects who receive at least 
one dose of study treatment. 
• This population will be based on the treatment 
the subject actually received. If a subject 
receives treatment differing from that assigned 
by the randomization schedule (for either a 
portion of or the entire time on study), they will 
be analysed based on the treatment taken for 
the majority of study participation. 
• Safety 
Intent-To-Treat 
(Exposed) 
• Comprise of all randomized subjects who 
receive at least one dose of study treatment. 
• This population will be based on the treatment 
to which the subject was randomized. 
• Any subject who receives a treatment 
randomization number will be considered to 
have been randomized. 
• Efficacy 
• Study Population 
• Health Outcomes 
Intent-To-Treat  
• Comprise of all randomized subjects. 
• This population will be based on the treatment 
to which the subject was randomized. 
• Any subject who receives a treatment 
randomization number will be considered to 
have been randomized. 
• Efficacy (sensitivity 
analyses) 
Per-Protocol 
• Comprise of all subjects in the ITT-E 
population with the exception of major protocol 
violators, e.g. violations which could affect the 
assessment of antiviral activity. 
• Protocol deviations that would exclude 
subjects from the PP population are defined in 
Section 5.1(Protocol Deviations) and Appendix 
1 (Protocol Deviation Management and 
Definition for Per-Protocol Population). 
• Efficacy (sensitivity 
analyses) 


 
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Population 
Definition / Criteria 
Analyses Evaluated 
Viral Genotypic  
• Comprise of all subjects in the ITT-E 
population with available On-treatment 
genotypic resistance data at the time 
confirmed virologic withdrawal criterion is met 
(see protocol, Section 4.5.1). 
• Genotypic 
Viral Phenotypic 
• Comprise of all subjects in the ITT-E 
population with available On-treatment 
phenotypic resistance data at the time 
confirmed virologic withdrawal criterion is met 
(see protocol, Section 4.5.1).  
• Phenotypic 
1. NOTES :  
• 
Please refer to Appendix 14: List of Data Displays which details the population to be used for each displays being 
generated. 
5.1. 
Protocol Deviations 
• 
Important protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarised and listed. 
• 
Important deviations which result in exclusion from the analysis population will also 
be summarised and listed. (Please refer to Appendix 1: Protocol Deviation 
Management and Definitions for Per Protocol Population)]. 
• 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations and deviations which may lead to exclusion from the 
analysis are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
• 
A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the eCRF. 
6. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
• 
There are no planned adjustments made for multiple centres in this study. 
• 
There are no planned adjustments for multiple comparisons or multiplicity. 
• 
There are no PK analyses planned in this study. 
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions.  


 
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Table 1 
Overview of Appendices 
Section Component 
12.1 
Appendix 1: Protocol Deviation Management and Definitions for Per Protocol 
Population 
12.2 
Appendix 2: Time & Events 
12.3 
Appendix 3: Assessment Windows 
12.4 
Appendix 4: Treatment States and Phases 
12.5 
Appendix 5: Data Display Standards & Handling Conventions 
12.6 
Appendix 6: Derived and Transformed Data 
12.7 
Appendix 7: Premature Withdrawals & Handling of Missing Data 
12.8 
Appendix 8: Values of Potential Clinical Importance 
12.9 
Appendix 9: Examination of Covariates and Subgroups 
12.10 
Appendix 10: Model Checking and Diagnostics for Statistical Analyses 
12.11 
Appendix 11: Snapshot 
12.12 
Appendix 12: Abbreviations & Trade Marks 
12.13 
Appendix 13: Final (End of Study) Analysis 
12.14 
Appendix 14: List of Data Displays 
12.15 
Appendix 15: Example Mock Shells for Data Displays 


 
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7. 
STUDY POPULATION ANALYSES 
7.1. 
Overview of Planned Analyses 
The study population analyses will be based on the ITT-E population, and will include a 
total column, unless otherwise specified. All displays are for the randomised phase only, 
unless otherwise stated. 
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 14: List of Data Displays. 
Table 2 
Overview of Planned Study Population Analyses 
Display Type 
Data Display’s Generated 
Table 
Listing 
Randomisation 
Randomisation 
 
Y [1] 
Subject Disposition 
Study Populations [2] 
Y 
Y [3] 
Study Recruitment [2] 
 
Y 
Age Categories 
Y 
 
History of Rescreened Subjects 
 
Y 
Reasons for Screen Failure [2]  
Y 
Y 
Subject Disposition 
Y [4,9] 
 
Reasons for Withdrawal by Visit 
Y 
Y 
Study Visit Dates   
 
Y 
Important Protocol Deviations 
Y 
Y 
Deviations leading to exclusion from PP 
Y 
Y 
Inclusion and Exclusion Criteria Deviations 
 
Y 
Demography 
Demographic Characteristics[10] 
Y 
Y 
Race & Racial Combinations[11] 
Y  
Y 
Hepatitis Status 
Y 
Y 
CDC Classification of HIV infection 
Y 
Y 
HIV Risk Factor 
Y 
Y 
Cardiovascular Risk Assessments at Day 1 
Y 
Y 
Distribution of Quantitative Plasma HIV-1 RNA 
Y 
 
Distribution of CD4+ Cell Counts 
Y 
 
History of Cardiac Therapeutic Procedures 
 
Y 


 
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Display Type 
Data Display’s Generated 
Table 
Listing 
Medical Conditions, Concomitant  Medications & Antiretroviral Therapy 
Medical Conditions (Current and Past) [12] 
Y  
Y[8] 
Medical Conditions: Sub-conditions (Current/Past) [12] 
Y  
Y[8] 
Concomitant Medications (non-ART) 
Y[5] 
Y[6,8] 
Prior and Concomitant ART Medications 
 
Y[7,8]  
Lipid Modifying agents (Baseline and Post-Baseline) 
Y 
 
Other  
IP Accountability [13] 
 
Y 
1. NOTES : 
• 
Y = Display Generated, T = Tables, L = Listings, IP = Investigational Product 
1. 
One listing of subjects randomised but not treated, and one listing of planned and actual treatment strata. 
2. 
All Subjects screened population. 
3. 
Listing only includes those who were excluded from at least one population. 
4. 
Randomised Phase only at Week 48 analysis; Combined Randomised Phase and Continuation Phase for End of 
Study analysis. 
5. 
Three separate tables, summarised by Ingredient ATC Level 1, Ingredient combinations and Combination term 
ATC Level 1 (EG Includes single-ingredient medications with multi-ingredient medications labelled according to 
the sum of their ingredients, e.g., “TYLENOL Cold and Flu” would appear as “CHLORPHENAMINE MALEATE + 
DEXTROMETHORPHAN HYDROBROMIDE + PARACETAMOL +  PSEUDOEPHEDRINE HYDROCHLORIDE” 
under the ATC headings for “Nervous System” and “Respiratory System” (the combination’s ATC classifications).) 
6. 
One listing for concomitant non-ART medications and one listing showing the relationship between verbatim text, 
ingredient and ATC Level 1. 
7. 
One listing for Prior ART, one listing for concomitant ART and one listing showing the relationship between 
verbatim text, ingredient, combination and ATC Level 4. 
8. 
Repeated for subjects at Mexico sites who experienced an adverse event, at End of Study reporting only. 
9. 
Subjects who have not been recorded as either completing or withdrawing from the study will be categorized as 
“Ongoing at time of the analysis” for summary purposes. 
10. Age, ethnicity, weight and height collected at screening (Day 1 for height) 
11. The five high level FDA race categories and designated Asian subcategories will be summarised along with all 
combinations of high level categories which exist in the data. The nine race categories collected will be 
summarised along with categories for mixed race. A by-subject listing of race will also be produced. 
12. Medical conditions will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
13. Dispensation information (dates and number of tablets dispensed and returned) 
 
8. 
PRIMARY STATISTICAL ANALYSES 
8.1. 
Efficacy Analyses 
The primary efficacy analyses will be based on the Intent-To-Treat (Exposed) population, 
unless otherwise specified. Summaries will be presented by treatment group with no total 
column.  
All displays are for the randomised phase only, unless otherwise stated. 


 
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8.1.1. 
Overview of Planned Efficacy Analyses 
Table 3 provides an overview of the planned efficacy analyses, with full details of data 
displays being presented in Appendix 14: List of Data Displays. 
Table 3 
Overview of Planned Efficacy Analyses 
Endpoints 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Proportion of Subjects with Plasma HIV-1 RNA <50c/ml at Week 48 – Snapshot 
Primary Analysis  
Y[1] 
 
 
Y[2] 
Y[3] 
 
Y[2] 
Treatment 
Heterogeneity across 
randomization strata 
Y 
 
 
 
 
 
 
<50 c/mL by 
Subgroups  [4] 
 
 
 
Y 
Y[5] 
 
 
Proportion of subjects without virologic (ERDF) or virologic/tolerability (TRDF) failure – Sensitivity 
analysis 
Kaplan-Meier 
estimates 
 
 
 
Y 
 
 
 
1. NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
1. 
Generated using the ‘Intent-to-Treat Exposed’ (primary), ‘Per-Protocol’ and ‘Intent-to-Treat’ (sensitivity) 
populations. 
2. 
Study outcomes (i.e., response below 50 c/mL, virologic failure or reason for no data in the window) based on the 
snapshot algorithm. 
3. 
Line plots, with 95% confidence intervals, for the proportion of subjects below 50 c/mL by treatment group at each 
visit. 
4. 
Baseline demography (age, race, country, CDC), HIV-1 subtype, Baseline CD4 and Baseline viral load 
5. 
Plot of 95% confidence intervals for the proportion of subjects below 50 c/mL by subgroup. 


 
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8.1.2. 
Planned Efficacy Statistical Analyses 
Primary Statistical Analyses 
Endpoint 
• Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using the Snapshot 
algorithm (Missing, Switch or Discontinuation = Failure) for the ITT-E population 
 
Snapshot Dataset 
• The Snapshot algorithm treats all subjects without HIV-1 RNA data at the visit of interest (due 
to missing data or discontinuation of IP prior to the visit window) as non-responders, as well as 
subjects who switch their concomitant ART prior to the visit of interest in certain scenarios. 
Since changes in ART are not permitted in this protocol, all such subjects who change ART will 
be considered non-responders. 
• Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA 
assessment while the subject is On-treatment within the visit of interest analysis window (see 
Section 12.3.1)  
• Full details of the Snapshot algorithm are in Appendix 11.  
 
Model Specification 
• The primary endpoint will be analysed using a stratified analysis with Cochran-Mantel-
Haenszel (CMH) weights, adjusting for Baseline plasma HIV-1 RNA ( ≤ vs. >100,000 c/mL) 
and CD4+ cell count (≤350 cells/mm3 or >350 cells/mm3).  
• The CMH estimate of the adjusted treatment difference will be calculated as a weighted 
average of strata-specific estimates of the treatment difference calculated within each of the 
following four Baseline analysis strata: 
o Plasma HIV-1 RNA ≤ 100,000 c/mL AND CD4+ ≤ 350 cells/mm3 
o Plasma HIV-1 RNA ≤ 100,000 c/mL AND CD4+ > 350 cells/mm3 
o Plasma HIV-1 RNA > 100,000 c/mL AND CD4+ ≤ 350 cells/mm3 
o Plasma HIV-1 RNA > 100,000 c/mL AND CD4+ > 350 cells/mm3 
• If nk is the number of DTG treated subjects, mk is the number of ATV treated subjects, and Nk = 
nk + mk is the total number of subjects in the kth stratum, then the CMH estimate is given by 
∑
∑
=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
 
       where, 
  
are CMH weights and dk are estimates of the differences in response proportions between the 


 
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Primary Statistical Analyses 
two treatment arms, rd-ra, for the kth strata. 
• The corresponding two-sided 95% CI will be calculated as 
)
ˆ
r(
aˆ
v
96
.1
ˆ
cmh
cmh
d
d
×
±
 
using the variance estimator, var(dcmh), given by [Sato, 1989 ], which is consistent in both 
sparse data and large strata.  The full equation for this variance estimate is provided in Section 
12.6.4. 
Model Results Presentation 
• Adjusted CMH estimate of the difference in the proportion of responders between each 
treatment group (DTG – ATV) and corresponding 95% confidence interval. 
• Non-inferiority will be concluded if the lower bound of the two-sided 95% confidence interval 
(CI) for the CMH adjusted difference in the proportion of patients who respond in the DTG 
group minus the proportion of patients who respond in the ATV group is greater than -12%.   
 
Sensitivity and Supportive Statistical Analyses 
1. Treatment Heterogeneity across randomization strata: 
• The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to test for one-
way homogeneity across the levels of each categorical variable, with each categorical 
variable considered separately.  
• Following Lui and Kelly [Lui, 2000] ½ will be added to each cell in any strata for which the 
stratum-specific rate estimates of either rd or ra are zero or one, and tests will be one-
sided.  
• Any heterogeneity found to be statistically significant will be explored and if necessary 
results will be reported for each level of the categorical variable. Investigation of 
heterogeneity will be confined to the primary. Tests of homogeneity will be assessed at the 
one-sided 10% level of significance. 
 
2. Per-protocol population analysis: 
• To assess the impact of major protocol deviations, statistical analysis will be repeated 
using the Per-protocol population and compared for consistency with the results from the 
primary ITT-E population analysis.  If both analyses show non-inferiority then the 
hypothesis that the antiviral effect of treatment with DTG/ABC/3TC FDC is superior to 
treatment with ATV+RTV+TDF/FTC FDC will be tested at the two-sided 5% level of 
significance.  Superiority will be declared if the lower end of the confidence interval is 
above 0% for the ITT-E population analysis. If superiority is declared the p-value for 
superiority will also be calculated. 
 
3. Intent-to-Treat population analysis: 
• Statistical analysis will be repeated using the Intent-to-Treat population and compared for 
consistency with the results from the ITT-E and PP populations. 
• In this analysis, subjects randomised but not exposed to study treatment will be classified 
as non-responders, which therefore address any selection bias that may occur given the 
open-label study design.  


 
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Sensitivity and Supportive Statistical Analyses 
4. Exploration of Subgroups: 
• A simple analysis for all the subgroups listed in Section 12.9.1 will be performed. This will 
show the proportion of subjects with plasma HIV-1 RNA <50 c/mL at the time of analysis 
(Week 48) based on the SNAPSHOT algorithm and will be presented by treatment group. 
• Unadjusted difference in proportions between treatment groups and corresponding two-
sided 95% CI will also be presented by treatment and subgroup, and a 95% CI for the 
(unadjusted) treatment difference in each subgroup. These results will also be presented 
graphically.  
• If the basic summary suggests an interaction, then a corresponding summary of study 
outcomes (i.e., response below 50 c/mL, virologic failure or reason for no data in the 
window) by subgroup will be produced. 
Note: These subgroup analyses will be exploratory and likely underpowered so that 
interpretation may therefore focus on point estimates as well as the lower bounds of 95% CIs 
for the treatment differences and response rates. Additionally, multiple comparisons are being 
made which inflates the risk of false positive findings. Therefore, if consistent findings across 
the multiple comparisons were observed then these analyses would still be suggestive of a 
generalizable finding of non-inferiority. 
5. Proportion of subjects without virologic (ERDF) or virologic/tolerability (TRDF) failure: 
• Estimated using the Kaplan-Meier nonparametric method based on the time to Confirmed 
Virologic Withdrawal (CVW) or treatment related/efficacy related discontinuation (i.e., drug-
related AE, protocol defined safety stopping criteria, or lack of efficacy) 
• Subjects who have not met CVW criteria and are ongoing in the study, or who have 
discontinued for reasons other than those related to treatment/lack of efficacy, will be 
censored. 
• The estimate of the standard error used to derive confidence intervals for the difference in 
proportions between treatment groups will be based on Greenwood’s formula [Kalbfleisch, 
1980] 
• The estimated proportion of subjects without Confirmed Virologic Withdrawal and not 
discontinued due to treatment related/efficacy related reasons at Week 48 will be 
presented by treatment group, along with estimated difference in proportions between 
treatment groups and its associated two-sided 95% CI.  
• The proportion of subjects with Confirmed Virologic Withdrawal will be summarized by visit. 
 


 
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9. 
SECONDARY STATISTICAL ANALYSES 
9.1. 
Efficacy Analyses 
9.1.1. 
Overview of Planned Efficacy Analyses 
The secondary efficacy analyses will be based on the Intent-To-Treat (Exposed) 
population, unless otherwise specified. All displays are for the randomised phase only, 
unless otherwise stated. 
Table 4 provides an overview of the planned efficacy analyses, with further details of 
data displays being presented in Appendix 14: List of Data Displays. 
Table 4 
Overview of Planned Efficacy Analyses 
Endpoints 
Absolute  
Change from Baseline  
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Plasma HIV-1 RNA Over Time  
Observed 
 
 
 
Y 
 
Y[1] 
Y 
 
 
 
Y 
 
 
 
Proportion of Subjects with Plasma HIV-1 RNA <400 & <50 copies/mL - Snapshot 
<50 c/mL by Visit 
 
 
 
Y[2] 
 
 
 
 
 
 
 
 
 
 
<400 c/mL by Visit 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
<400 c/mL Outcomes 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
Confirmed Virologic Withdrawal (CVW) 
CVW by Visit 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
HIV-1 RNA distribution 
at time of suspected 
and confirmed 
Virologic withdrawal 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
CD4+  Cell Counts Over Time 
CD4+ Observed 
 
 
 
Y 
 
 
Y 
 
 
 
Y 
 
 
Y 
Post-baseline HIV-1 Disease Progression[3] 
HIV Conditions 
including Recurrences 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
HIV Conditions 
excluding Recurrences 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
HIV Disease 
Progressions 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
NOTES : 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 


 
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1. 
Individual plasma profiles  
2. 
Repeated for End of Study using Observed data. 
3. 
HIV disease progressions categories: CDC Category A at baseline to CDC Category B event; CDC Category A at 
baseline to CDC Category C event; CDC Category B at baseline to CDC Category C event; CDC Category C at 
baseline to new CDC Category C event and CDC Category A, B or C at baseline to death.  
 
 
9.2. 
Safety Analyses 
9.2.1. 
Overview of Planned Analyses 
The safety analyses will be based on the Safety population, presented by treatment group 
with a total column unless otherwise specified. 
The observed case (OC) dataset will be used, which contains the data that is available at a 
particular timepoint, with no imputation for missing values, unless otherwise stated. 
All displays are for the randomised phase only, unless otherwise stated. 
Table 5 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays. 
Table 5 
Overview of Planned Safety Analyses 
Endpoint 
 
Absolute 
Change from Baseline 
Max Post BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
Exposure 
Extent of Exposure 
Y[1] 
 
 
Y[2,14] 
 
 
 
 
 
 
 
 
Adverse Events[3] 
All AEs by SOC and 
Toxicity[5] 
Y 
 
 
Y[4] 
 
 
 
 
 
 
 
 
Common AEs by freq 
[6] 
Y 
Y[
16] 
 
 
 
 
 
 
 
 
 
 
Common Grade 2-4 
AEs [6] 
Y 
 
 
 
 
 
 
 
 
 
 
 
All Drug-Related AEs 
by SOC and toxicity[5] 
Y 
 
 
 
 
 
 
 
 
 
 
 
Common Drug-related 
Grade 2-4 AEs [6] 
Y 
 
 
 
 
 
 
 
 
 
 
 
All SAEs by SOC 
Y[1] 
 
 
 
 
 
 
 
 
 
 
 
Reason for 
Considering as a 
Serious Adverse Event 
(FDA) 
 
 
 
Y  
 
 
 
 
 
 
 
 
All Drug-Related SAEs 
Y 
 
 
 
 
 
 
 
 
 
 
 


 
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Endpoint 
 
Absolute 
Change from Baseline 
Max Post BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
by SOC 
Fatal SAEs  
 
 
 
Y 
 
 
 
 
 
 
 
 
Non-Fatal SAEs 
 
 
 
Y 
 
 
 
 
 
 
 
 
Withdrawal AEs 
Y[1] 
 
 
Y 
 
 
 
 
 
 
 
 
Common Non-Serious 
AEs (FDAAA) 
Y 
 
 
 
 
 
 
 
 
 
 
 
Number of 
occurrences of 
Common Non-serious 
AEs by SOC 
(EudraCT) 
Y 
 
 
 
 
 
 
 
 
 
 
 
Number of 
occurrences of SAEs, 
Drug-related AEs, 
Fatal SAEs, and Drug-
related SAEs 
(EudraCT) 
Y 
 
 
 
 
 
 
 
 
 
 
 
AEs of Subjects at 
Mexico sites 
 
 
 
Y[18] 
 
 
 
 
 
 
 
 
SAEs of Subjects at 
non-Mexico sites 
 
 
 
Y[18] 
 
 
 
 
 
 
 
 
Pre-treatment AEs 
 
 
 
Y 
 
 
 
 
 
 
 
 
CV events 
 
 
 
Y 
 
 
 
 
 
 
 
 
PSRAE 
 
 
 
Y[17] 
 
 
 
 
 
 
 
 
Laboratory Values Over Time 
Clinical Chemistry  
 
 
 
Y [7] 
Y 
 
 
 
 
 
 
 
Lipids (%) 
 
 
 
 
Y 
 
 
 
 
 
 
 
Fasted Lipid 
(Triglycerides and 
TC/HDL ratio) analysis 
 
 
 
 
Y[22] 
 
 
 
 
 
 
 
Hematology  
 
 
 
Y [7] 
Y 
 
 
 
 
 
 
 
Urine Dipstick 
 
 
 
Y [7] 
Y 
 
 
 
 
Y 
 
 
Urine Concentration 
 
 
 
Y [7] 
Y 
 
 
 
 
 
 
 
Proteinuria shifts 
 
 
 
 
 
 
 
 
 
Y[9] 
 
 
Liver Chemistries 
 
 
 
 
 
 
 
 
 
Y[8] 
 
 
NCEP shifts in lipids 
 
 
 
 
 
 
 
 
Y 
Y[10] 
 
 
Total Cholesterol/HDL 
ratio  
 
 
 
 
Y 
 
 
 
 
 
 
 
Bone markers 
 
 
 
 
Y 
 
 
 
 
 
 
 


 
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Endpoint 
 
Absolute 
Change from Baseline 
Max Post BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
Treatment Emergent Laboratory Toxicities[11] 
Clinical Chemistry 
 
 
 
 
 
 
 
 
Y 
 
 
 
Hematology 
 
 
 
 
 
 
 
 
Y 
 
 
 
Other 
ECG Findings 
 
 
 
Y[21] 
 
 
 
 
 
 
 
 
Vital Signs 
 
 
 
Y 
 
 
 
 
 
 
 
 
Abacavir HSR 
Y 
 
 
Y [12] 
 
 
 
 
 
 
 
 
Liver Assessment 
 
 
 
Y [13] 
 
 
 
 
 
 
 
 
Hepatobiliary 
Abnormality criteria 
Y [1,19] 
 
 
 
 
 
 
 
 
 
 
 
Columbia suicidality 
Y 
 
 
Y [15] 
 
 
 
 
 
 
 
 
Subjects who became 
Pregnant 
 
 
 
Y 
 
 
 
 
 
 
 
 
Patient Profiles 
 
 
 
Y [20] 
 
 
 
 
 
 
 
 
NOTES : 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.  
1. 
Randomisation Phase only at Week 48 analysis; Combined Randomisation Phase and Continuation Phase for 
End of Study analysis. 
2. 
Includes reason for any dose change/interruption. 
3. 
Adverse events will be coded using the MedDRA coding dictionary to give a preferred term and a system organ 
class. Summaries include only Post-baseline AEs with onset date up to cut-off date for reporting effort, listings 
include all AEs including those with onset pre- or post-treatment. 
4. 
One listing of all AEs including verbatim text and preferred term, one showing the relationship between verbatim 
text, preferred term and SOC and another giving subject numbers for individual all treatment emergent AEs.  
5. 
For AEs reported more than once by a subject, the most severe intensity will be included. 
6. 
Common AEs are those with >5% incidence in either treatment group summarised by frequency. 
7. 
Listings for subjects with abnormalities for potential clinical concern, defined as any Grade1-4 toxicity.  
8. 
Scatter plot of baseline vs. maximum post-baseline for ALT. Scatter plot of maximum ALT vs. maximum Bilirubin.  
9. 
Shift table summarising baseline vs. maximum post-baseline result for urine dipstick protein 
10. Bar chart for LDL, HDL, TC, Trig and HDL/TC ratio. 
11. Treatment Emergent Laboratory Toxicities - See protocol Section 11.2, Appendix 2. 
12. Separate listings for exposure to abacavir, history of drug allergies, family conditions, skin rash, symptoms, vital 
signs, individual symptoms and diagnostic category assignment. 
13. Separate listings for time of event from trt, RUCAM score, biopsy, imaging, past/ current conditions & FU 
14. Repeated for subjects at Mexico sites at End of Study reporting. 
15. Includes Baseline and lists all visits for a subject who reports any ideation or behaviour at any visit. 
16. Plots of incidence rates and relative risk with 95% CI for DTG vs. ATV. 
17. Four PSRAE listings: Event and Description (Section 1- Section 2), Possible Cause (Section 3), Section 4 and 
Section 5- Section 8. 
18. Only for End of Study reporting 
19. One summary of subjects and another table showing Subject Ids. 
20. Patient profiles for subjects meeting protocol defined liver stopping criteria and for patients with virologic failure. 
Patient profiles can also be provided for any other subjects, as necessary for medical review. 


 
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21. Only collected when a Cardivascular event occurs. 
22. Primary analysis method is multiple imputation MAR. Repeated for sensitivity analyses using OC, LOCF and 
MMRM.  
9.2.2. 
Planned Safety Statistical Analyses 
Statistical Analyses 
Endpoints 
• Change from Baseline in fasted triglycerides at Week 48. 
• Change from Baseline in fasted TC/HDL ratio at Week 48. 
Covariates 
• Baseline Plasma HIV-1 RNA (≤100,000 c/mL c/mL or >100,000 c/mL c/mL) 
• Baseline CD4+ cell count (≤350 cells/mm3 cells/mm3 or >350 cells/mm3) 
• Fasted triglycerides (mmol/L) and fasted TC/HDL measurements at Baseline, Week 12 and 
Week 36 
• Age (>=50 or <50) 
Data Handling 
• If a subject is on lipid-lowering therapy from Baseline, they will be excluded from the analysis.  
• If a subject initiates lipid-lowering therapy during the study, all visits after that date will be set 
to missing.  
• All other data remains as is (observed or missing). 
• A multiple imputation technique will be used to deal with the missing data at week 48. 
Model Specification 
• Multiple imputations will be drawn from a multivariate normal model for the data (including 
covariates) with a Markov Chain Monte Carlo (MCMC) approach used to estimate posterior 
distributions.  A non informative prior will be used.  A seed of 18 will be used in the SAS 
program.  Where a subject has a monotone or non-monotone pattern of missingness, all of 
their missing observations can be imputed under this approach.  
• Imputations will be drawn separately for subsets of subjects according to their treatment 
group, i.e., based on means and variance-covariances from the same treatment group 
(Missing At Random (MAR) approach) conditioning on observed covariates listed above. This 
will be known as the MAR method.  
• The imputations will be carried out 1,000 times. An ANOVA will be performed on each 
datasets produced adjusting for baseline triglycerides (<5.65 mmol/L or ≥5 .65 mmol/L)  or 
TC/HDL ratio (<3.5 or ≥3.5), age, baseline plasma HIV-1 RNA and CD4+ cell count, 
regardless of their significance. PROC MIANALYZE in SAS will be used to combine the 
1,000 estimated means and difference to produce one estimated mean with 95% CI and 
associated p-value for the adjusted mean difference between each treatment group at Week 
48. 
• Interactions between treatment and each of the covariates will not be assessed. 
Model Checking & Diagnostics 
• Refer to Appendix 10: Model Checking and Diagnostics for Statistical Analyses. 
Model Results Presentation 
• Adjusted means and corresponding standard error of means (SEs) will be presented for each 
treatment, together with estimated treatment difference (DTG – ATV) and corresponding 95% 
confidence interval and p-value.  


 
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Statistical Analyses 
Sensitivity Analyses 
• Two ANCOVA sensitivity analyses will be performed as follows: 
• using the standard Observed Case (OC) dataset, with no adjustment or 
imputation for withdrawing, initiating lipid-lowering agents or other missing data.  
• using the Lipid LOCF dataset (see Section 12.7.2.2), but also carrying forward 
the last observation to any missing visits. 
• A MMRM analysis, with time crossed with treatment, age, baseline triglycerides (<5.65 
mmol/L or ≥5 .65 mmol/L) or TC/HDL ratio (<3.5 or ≥3.5),baseline Plasma HIV-1 RNA and 
CD4+ cell count will also be conducted.  


 
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10. 
OTHER STATISTICAL ANALYSES 
10.1. 
Health Outcomes 
The Health Outcomes analyses will be based on the ITT(E) population and presented by 
treatment group unless otherwise specified. 
All displays are for the randomised phase only, unless otherwise stated. 
Table 6 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays. 
Table 6 
Overview of Planned Health Outcome Analyses 
Endpoints 
Absolute  
Change from Baseline  
Stats 
Analysis 
Summary 
Individual 
Stats 
Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Quality of Life  
SF-12 individual item 
scores by Visit - LOCF 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
SF-12 Total score, PCS 
and MCS by Visit - 
LOCF & Observed 
 
 
 
Y 
 
 
 
 
 
 
Y[1] 
 
 
 
Treatment satisfaction  
HIVTSQs individual item 
scores by Visit - LOCF 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
HIVTSQs (at Weeks 4, 
12, 24 and 48) - LOCF & 
Observed 
Y[2] 
 
 
 
 
 
Y 
 
 
 
 
 
 
 
NOTES : 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data. 
1. 
Change from Baseline at Week 48 
2. 
Separate summaries for Total score, Lifestyle/ease sub-score and General Satisfaction/Clinical sub-score.  
 
Statistical Analyses 
Endpoint(s) 
• 
HIVTSQ total score 
• 
HIVTSQ general satisfaction/clinical sub-score (items 1, 2, 3, 9, and 10) 
• 
HIVTSQ lifestyle/ease sub-scores (items 4, 5, 6, 7 and 8) 
Model Specification/Analysis Methodology 
• 
Wilcoxon rank sum tests. 
• 
No adjustment for multiplicity will be applied as these analyses will be considered exploratory. 
• 
An LOCF dataset will be used as described in Section 12.7.2.2. 
• 
The analysis will be repeated using an Observed Case dataset (as supportive analyses). No adjustment for 


 
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multiplicity will be applied as these analyses will be considered supportive. 
Model Results Presentation 
• 
Summary statistics will be presented by treatment group, with a p-value for the difference in the mean based 
on the Wilcoxon rank sum test.  
 
10.2. 
Virology 
The virology analyses of genotype data will be based on the Genotypic population, and 
analyses of phenotype data will be based on the Phenotypic population. Summaries will be 
presented by treatment group unless otherwise specified. 
All displays are for the randomised phase only, unless otherwise stated. 
Table 7 provides an overview of the planned analyses, with further details of data displays 
being presented in Appendix 14: List of Data Displays. 
Table 7 
Overview of Planned Virology Analyses 
Endpoint  
Absolute 
Change from Baseline 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
Genotypic resistance 
Incidence of genotype at 
time of CVW[3] 
Y[1]  
 
 
Y 
Y[1] 
 
 
Y 
Phenotypic resistance 
Incidence of phenotype 
at time of CVW[3] 
Y[2[ 
 
 
Y 
 
 
 
 
INI replication capacity 
at time of CVW[3] 
 
 
 
Y 
 
 
 
 
Fold Change at time of 
CVW[3] 
Y 
 
 
 
Y 
 
 
 
1. NOTES : 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual subject observed raw data.    
1. 
 Separate outputs for INI and NRTI/NNRTI/PI mutations 
2. 
Separate outputs by phenotypic cut-off and by number of drugs to which subjects are resistant. 
3. 
Sample used for resistance testing is taken at the suspected visit date, and only tested once a subject confirms 
virological failure at a subsequent visit.   


 
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11. 
REFERENCES 
• Anderson KM, Wilson PWF, Odell PM, Kannel WB. An updated coronary risk 
profile. A statement for health professionals. Circulation. 1991;83:356-362.  
• Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York:John 
Wiley; 1981.  
• GlaxoSmithKline Document Number 2013N161649_01. Study ID ING117172.  A 
Phase IIIb, Randomized, open-label study of the safety and efficacy of 
dolutegravir/abacavir/lamivudine once daily compared to atazanavir and ritonavir 
plus tenofovir/emtricitabine once daily in HIV-1 infected antiretroviral therapy naïve 
women. Report Date 12-AUG-2013. 
• Grundy S.M., et al. Executive summary of the third report of the National Cholesterol 
Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of 
High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285 
(19):2486-2497.  
• HIVTSQ user guidelines 
• Kalbfleisch J.D., Prentice R.L. The Statistical Analysis of Failure Time Data. 1st ed. 
New York:John Wiley & Sons; 1980.  
• Lui K.J., Kelly C. A Revisit on Tests for Homogeneity of the Risk Difference, 
Biometrics, 2000;56:309-315. 
• Sato T. On the variance estimator for the Mantel-Haenszel risk difference. 
Biometrics. 1989;42:311-323.  
• Ware, JE Jr. A 12-Item Short-Form Health Survey: construction of scales and 
preliminary tests of reliability and validity. Medical Care 1996. 0025-7079. 34(3):220 
Lippincott Williams & Wilkins, Inc. 
• Wensing AM, Calvez V, Günthard HF et al. 2014 Update of Drug Resistance 
Mutations in HIV-1. Topics in Antiviral Medicine 2014; 22(3): 642-650. 
• Woodcock A, Bradley C (2001). Validation of the HIV Treatment Satisfaction 
Questionnaire (HIVTSQ). Quality of Life Research. 10:517-531. 
• Woodcock A, Bradley C (2006). Validation of the Revised 10-item HIV Treatment 
Satisfaction Questionnaire Status Version and New Change Version . Value in 
Health. 9:320-333. 


 
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12. 
APPENDICES 
Section 
Appendix 
RAP Section 5 : Analysis Populations 
Section 12.1 
Appendix 1: Protocol Deviation Management and Definitions for Per Protocol 
Population 
RAP Section 6 : General Considerations for Data Analyses & Data Handling Conventions 
Section 12.2 
Appendix 2: Time and Events 
Section 12.3 
Appendix 3: Assessment Windows 
Section 12.4 
Appendix 4: Treatment States & Phases 
Section 12.5 
Appendix 5: Data Display Standards & Handling Conventions 
• Study Treatment & Sub-group Display Descriptors 
• Baseline Definitions & Derivations 
• Reporting Process & Standards 
Section 12.6 
Appendix 6: Derived and Transformed Data 
• General, Study Population & Safety 
• Efficacy 
• Virology 
• Health outcomes 
Section 12.7 
Appendix 7: Premature Withdrawals & Handling of Missing Data 
• Premature Withdrawals 
• Handling of Missing Data 
Section 12.8 
Appendix 8: Values of Potential Clinical Importance 
Section 12.9 
Appendix 9: Examination of Covariates and Subgroups 
Section 12.10 
Appendix 10: Model Checking and Diagnostics for Statistical Analyses 
Section 12.11 
Appendix 11: Snapshot 
Other RAP Appendices 
Section 12.12 
Appendix 12: Abbreviations & Trade Marks 
Section 12.13 
Appendix 13: Final (End of Study) Analysis 
Section 12.14 
Appendix 14: List of Data Displays 
Section 12.15 
Appendix 15: Example Mock Shells for Data Displays 
 
 
 


 
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12.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
12.1.1. 
Exclusions from Per Protocol Population 
Protocol deviations leading to exclusion from PP population are those deviations which  
• may directly impact the efficacy endpoint of HIV-1 RNA; or 
•  lead to permanent discontinuation of IP/withdrawal and hence indirectly impact the 
efficacy endpoint by causing data to be missing. 
The following criteria define the protocol deviations which, if they occur prior to an 
analysis timepoint of interest, will lead to exclusion of a subject from the Per-Protocol 
population for that analysis. Potential protocol deviations leading to exclusion from PP 
population will be reviewed by the study team to confirm that they meet these criteria.  
This review will occur before the clinical database has been frozen for analysis.  
A subject meeting any of the following criteria will be excluded from the Per Protocol 
population: 
Number 
Exclusion Description 
01 
Subject deviates from any inclusion or exclusion criteria, as recorded in the eCRF 
02 
Subject took/received incorrect IP, i.e., other than the one to which they were 
randomized for greater than 10% of the total time On-treatment 
03 
Interruption of IP for greater than 10% of the total time On-treatment, for reasons 
other than treatment-related adverse events/laboratory abnormalities, based on 
eCRF IP exposure forms (or CONMEDS eCRF forms for locally prescribed RTV 
during supply issues) 
04 
Prohibited medications: Receiving ART medication other than that 
prescribed/allowed by the study for a duration of >2 consecutive weeks or receiving 
non-ART medication that would potentially impact exposure or response to therapy 
with duration taken into consideration 
05 
Permanent discontinuation of IP/withdrawal due to a reason of “Protocol Deviation” 
(as recorded in the eCRF). 
 


 
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12.2. 
Appendix 2: Time & Events 
12.2.1. 
Protocol Defined Time & Events 
Procedures 
Scree
na 
D
ay 
1 
Randomized Phase 
Continuat
ion 
Phasek  
Withdra
wal 
Follo
w-upl 
Clinic Visits 
Conta
ct at 
Wk 8 
18, 
30, 
42r 
Every 12 
weeks 
after 
Week 48 
Wee
k 
4 
Wee
k 
12 
Wee
k 
24 
Wee
k 
36 
Wee
k 
48 
Clinical and Other Assessments 
Written informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusio
n criteriab 
X 
X 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Prior ART history 
X 
 
 
 
 
 
 
 
 
 
 
Medical historyc 
 
X 
 
 
 
 
 
 
 
 
 
Current medical 
conditions 
 
X 
 
 
 
 
 
 
 
 
 
HIV risk factors 
and mode of 
transmission 
 
X 
 
 
 
 
 
 
 
 
 
CDC HIV-1 
classification 
X 
X 
 
 
 
 
 
 
 
 
 
HIV associated 
conditions 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Cardiovascular 
risk assessmentd 
 
X 
 
 
 
 
 
 
 
 
 
Columbia 
Suicidality 
Severity Rating 
Scale 
 
X
u 
X 
X 
X 
X 
X 
 
X 
X 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Limited physical 
examinations 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
12-lead ECGt 
X 
 
 
 
 
 
 
 
 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious adverse 
events 
Xj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SF-12w 
 
X 
 
 
X 
 
X 
 
 
X 
 
HIVTSQw 
 
 
X 
X 
X 
 
X 
 
 
X 
 
Confirm 
understanding of 
study  and 
management/toler
ability of regimen 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Assessments 
Plasma for HIV 
genotyping 
X 
 
 
 
 
 
 
 
 
 
 


 
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Procedures 
Scree
na 
D
ay 
1 
Randomized Phase 
Continuat
ion 
Phasek  
Withdra
wal 
Follo
w-upl 
Clinic Visits 
Conta
ct at 
Wk 8 
18, 
30, 
42r 
Every 12 
weeks 
after 
Week 48 
Wee
k 
4 
Wee
k 
12 
Wee
k 
24 
Wee
k 
36 
Wee
k 
48 
Quantitative 
plasma HIV-1 RNA 
X 
X 
X 
X 
Xn 
Xn 
Xn 
 
Xn 
X 
 
Lymphocyte 
subset  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Plasma for 
storagee 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
HLA-B* 5701 
testingq 
X 
 
 
 
 
 
 
 
 
 
 
Clinical chemistry 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Fasting lipids and 
glucosef 
 
X 
 
X 
X 
X 
X 
 
 
 
 
Urinalysis and 
spot urine for 
protein analysisg 
 
X 
 
 
X 
 
X 
 
Xp 
Xm 
X 
Pregnancy testh 
S 
U 
S 
S 
S 
S 
S 
 
S 
S 
 
HBsAg and 
hepatitis C 
antibody 
X 
 
 
 
 
 
 
 
 
 
 
Pharmacogenetic 
samplei 
 
X 
 
 
 
 
 
 
 
 
 
Bone marker 
analytes (blood)v 
 
X 
 
 
X 
 
X 
 
 
 
 
Investigational Product 
IVRS 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Dispense IP 
 
X 
X 
X 
X 
X 
Xo 
 
X 
 
 
IP accountability 
(pill counts) 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
 
a. 
The 14-day Screening period maybe extended to 28 days.  Randomization may occur as soon as all Screening 
results are available. 
b. 
Inclusion/exclusion criteria will be fully assessed at the Screening visit.  Changes between the screening visit 
and the Day 1 visit should be assessed to ensure eligibility, including additional assessments performed at Day 
1. 
c. 
Full medical history will be collected. Targeted medical history assessments will include cardiovascular, 
metabolic (e.g., Type I or II DM), psychiatric (e.g, depression) and renal (e.g., nephrolithiasis, nephropathy, 
renal failure) disorders. 
d. 
 Assessment for cardiovascular risk will include height, weight, blood pressure, smoking history, medical 
conditions, and family history of premature cardiovascular disease 
e. 
Plasma samples for storage will be collected at each visit for possible future analyses (including but not limited 
to HIV-1 RNA genotypic and phenotypic analyses, HIV-1 RNA levels, and immunological parameters).  These 
samples will be used when needed such as when samples are lost or arrive at the laboratory unevaluable.  
Additionally, these samples will be used for genotypic and/or phenotypic analyses when subjects meet 
confirmed virologic withdrawal criteria. 


 
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f. 
An overnight fast is preferred, however a minimum of a 6 hour fast is acceptable. 
g. 
A morning specimen is preferred. 
h. 
Pregnancy testing. Women of childbearing potential only. S=serum, U=urine. Remind females of reproductive 
potential of the need to avoid pregnancy while in study and adherence to the study’s contraception 
requirements. 
i. 
Informed consent for optional pharmacogenetics (PGx) research must be obtained before collecting a sample. 
Collection of the PGx sample at Day 1 is preferred, however this sample may be collected at any time during the 
study. 
j. 
Only SAEs related to study participation or to a concomitantly administered GSK product will be collected 
between obtaining informed consent and administration of IP at Day 1. 
k. 
For subjects who completed randomized DTG/ABC/3TC FDC through Week 48 and entered into DTG/ABC/3TC 
FDC Continuation Phase: subjects completing the DTG/ABC/3TC FDC Continuation Phase must return to the 
clinic when transitioning to commercial supplies.  Conduct study assessments as specified per the Week 36 
schedule at this end of Continuation Phase visit. 
l. 
A Follow up visit may be conducted approximately 4 weeks after the last dose of study provided IP, and is 
required only if the subject has ongoing AEs or lab abnormalities at the last on study visit.  The assessments 
performed should reflect what is considered medically necessary to assess the event(s). 
m. Conduct assessments at Week 48 OR at the Withdrawal visit for subjects who discontinue from the study prior 
to Week 48, but not both. 
n. 
Beginning at Week 24, subjects with plasma HIV-1 RNA ≥50 but <400 c/mL who elect to remain in study must 
return every 4-6 weeks for collection of samples for HIV-1 RNA determination and plasma for storage. Genotype 
and phenotype testing will only be performed with confirmed HIV-1 RNA ≥400 c/mL. 
o. 
For subjects receiving DTG/ABC/3TC FDC in Continuation Phase only 
p. 
Will be tested every 24 weeks (not every 12 weeks) 
q. 
Documentation that the subject had been screened for, and is negative for the HLA-B*5701 allele is acceptable. 
r. 
Contacts at Week 8,18, 30 and 42 are mandatory but may be conducted as a telephone, clinic or home visit (or 
other type of visit as agreed with GSK). 
s. 
Limited physical examination to include blood pressure at Baseline (recorded in eCRF) for Framingham score 
assessment, and weight at each visit (recorded in eCRF at Baseline and on lab requisition at all visits) for 
determination of CrCL. Blood pressure to be measured after resting in a semi-supine position for at least 
5 minutes.   
t. 
A 12-lead electrocardiograph (ECG) will be performed after resting in a semi-supine position for at least 5 
minutes.   
u. 
On Day 1, the Columbia Suicidality Severity Rating Scale (conducted by voice response system) is to be 
administered prior to randomization. 
v. 
Blood sample for bone marker assessment.  Only the result for 25 hydroxy-vitamin D will be reported to the 
investigator. 
w. SF-12 and HIV Treatment Satisfaction Questionnaire (HIVTSQ) is recommended to be administered at the 
beginning of the visit.  
 
12.3. 
Appendix 3: Assessment Windows 
Laboratory data, vital signs, ECGs, health outcomes assessments, and genotypic and 
phenotypic data will be assigned to assessment windows according to actual dates rather 
than the nominal visit labels as recorded on the eCRF or in the laboratory database. The 
CVW algorithm will be derived using nominal CRF visit rather than using the assessment 
window defined below. 
A window around a target Study Day will typically include all days from the midpoints 
between it and the target Study Days of the previous and the proceeding visits.  In 
general, the nominal target study day for week w is (7*w)+1. 


 
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12.3.1. 
Definitions of Assessment Windows for Analyses 
Analysis Set 
/ Domain 
Parameter      
(if applicable) 
Target  
Analysis Window 
Analysis 
Timepoint 
Beginning 
Timepoint 
Ending 
Timepoint 
All 
All 
-28 
<=-4 
<=-4 
Screening 
 
 
1 
-3 
1 
Day 1 
 
 
29 
2 
56 
Week 4 
 
 
85 
57 
126 
Week 12 
 
 
169 
127 
210 
Week 24 
 
 
253 
211 
294 
Week 36 
 
 
337 
295 
Date of Week 
48 visit 
Week 48 
 
 
421 
Date of Week 
48 visit +1 
462 
Week 60 
 
 
7*w + 1 
(7*w - 41) 
 
(7*w + 42) 
Week w 
w = 72, 84, 
96,… 
 
 
Study Day of last dose + 
28 
> (Study Day 
of last dose + 
1) 
- 
Follow-up 
1. NOTES : 
• 
For parameters which are not scheduled to be assessed at particular visits, the all- inclusive windows defined will 
still be used.  
• 
Data summaries will only report scheduled visits. Assessments at unscheduled visits will be included for ‘any time 
On-treatment’ time points and in data listings, as well as algorithms that make use of additional data (e.g., 
Snapshot). 
1.  
12.4. 
Appendix 4: Treatment States & Phases 
12.4.1. Treatment Phases 
All displays are for the randomised phase only, unless specified otherwise.  
Data collected from both arms up to and including the date of the Week 48 visit, or 
unscheduled Week 48 visit date, will be considered to be during the Randomised Phase 
of the Study. 
Data collected from the DTG/ABC/3TC FDC arm after Week 48, or unscheduled Week 
48 visit, to the end of the study will be considered to be during the Continuation Phase of 
the Study. 
12.4.2. 
Treatment States 
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment. 


 
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12.4.2.1. 
Treatment States for Laboratory, HIV Associated Conditions, Vital 
Signs, ECGs, Health Outcomes and Genotypic and Phenotypic Data 
Treatment State 
Definition 
Pre-Treatment 
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 1 
Post-Treatment 
Date > Study Treatment Stop Date +1 
1. NOTES:  
• 
If the study treatment stop date is missing then the assessment will be considered to be On-Treatment 
 
12.4.2.2. 
Treatment States for AE Data 
For adverse events, partial AE start date will use imputation as described in Section 
12.7.2.1. In the case of a completely missing start date, the event will be considered to 
have started On-treatment unless an end date for the AE is provided which is before start 
of investigational product; in such a case the AE is assigned as Pre-treatment. 
Treatment State 
Definition 
Pre-Treatment 
AE Start Date < Study Treatment Start Date 
On-Treatment 
If AE onset date is on or after treatment start date & on or before treatment stop date. 
Study Treatment Start Date  ≤ AE Start Date ≤ Study Treatment Stop Date 
Post-Treatment 
If AE onset date is after the treatment stop date. 
AE Start Date > Study Treatment Stop Date  
Onset Time  
Since 1st Dose 
(Days) 
If Treatment Start Date ˃ AE Onset Date = AE Onset Date - Treatment Start Date 
If Treatment Start Date ≤ AE Onset Date = AE Onset Date - Treatment Start Date +1 
Missing otherwise. 
Duration (Days)  
AE Resolution Date – AE Onset Date + 1 
Drug-related 
If relationship is marked ‘YES’ on Inform/CRF OR value is missing. 
 
NOTES:  
• 
If the study treatment stop date is missing, then any event with a start date on or after study treatment Start Date 
will be considered to be On-treatment.  
• 
If the start date of the AE is after study treatment Stop Date but has been recorded as potentially related to study 
treatment, then it will be classified as On-treatment. 
 


 
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12.4.2.3. 
Treatment States for Prior/Concomitant/Post-Therapy Medications Data 
• Prior medications: Those taken (i.e., started) before the start date of investigational 
product.  
• Concomitant medications: Those taken (i.e., started or continued) at any time between 
the start date and stop date of study treatment, inclusive. Prior medications that were 
continued during this period are also considered as concomitant medications.  
• Post treatment medications: Those started after the stop date of study treatment. 
Concomitant medications that were continued during this period are also considered 
as post-treatment medications. 
It will be assumed that medication has been taken on the date in which it is reported as 
started or stopped. For any medication starting on the same date as study treatment, it will 
be assumed that the medication was taken after the subject started taking study treatment. 
ART medications will also be classified as prior, concomitant and/or post-treatment 
according with the following modifications: 
• ART starting on study treatment stop date will be considered as only post-
treatment and not concomitant. It is expected that after discontinuation of study 
treatment, a subject may immediately begin taking another ART. 
• ART stopping on study treatment start date will only be considered as prior and 
not concomitant. 
• Any ART entered on the Prior ART eCRF with partial end date will be assumed 
to have finished before Screeninig. 


 
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ING117172 
 
37 
 
 
Pre-
treatment 
On-treatment 
Post-treatment 
Prior 
Conco-
mitant 
Post 
(a) 
xx 
IP Start Date 
 
IP Stop Date 
IP Stop Date+1 
 
Y 
N 
N 
(b) 
x  
x 
 
Y 
Y 
N 
(c) 
x  
 
x 
Y 
Y 
Y 
(d) 
 
xx 
 
N 
Y 
N 
(e) 
 
x 
x 
N 
Y 
Y 
(f) 
 
 
xx 
N 
N 
Y 
(g) 
?x 
 
 
Y 
N 
N 
(h) 
? 
x 
 
Y* 
Y 
N 
(i) 
? 
 
x 
Y* 
Y* 
Y 
 
 
 
 
 
 
 
(j) 
x  
 
? 
Y 
Y** 
Y** 
(k) 
 
x 
? 
N 
Y 
Y** 
(l) 
 
 
x? 
N 
N 
Y 
(m) 
? 
 
 
 
 
? 
Y*** 
Y*** 
Y*** 
 
 
 
 
 
 
 
 
 
 
(n) 
x 
x 
 
 
 
 
Y 
Y 
N 
(o) 
? 
x 
 
 
 
 
Y* 
Y 
N 
(p) 
 
x 
x 
 
 
 
N 
Y 
N 
(q) 
 
x 
 
x 
 
 
N 
Y 
N 
(r) 
 
 
 
x 
 
x 
N 
Y 
Y 
(s) 
 
 
 
x 
 
? 
N 
Y 
Y** 
(t) 
 
 
 
 
x 
x 
N 
N 
Y 
(u) 
 
 
 
 
x 
? 
N 
N 
Y 
(v) 
 
 
x 
 
x 
 
N 
Y 
Y 
1. x = start/stop date of medication 
2. ? = missing start/stop date of medication 
3. * If a medication is stopped On-treatment or Post-treatment and no start date is recorded it will be assumed that 
the medication was ongoing from the Pre-treatment phase 
4. ** If a medication is started Pre-treatment or On-treatment and no stop date is recorded then usage will be 
assumed to be ongoing for the remainder of the study 
5. *** If a medication has no start or stop date it will be assumed that the medication was ongoing from the Pre-
treatment phase to the Post-treatment phase 
12.4.3. 
Treatment Phases and States 
On-treatment and Post-treatment assessments and events will be classified as occurring 
during the Randomized Phase or the Continuation Phase of the study as follow: 
• 
If a subject did not enter the Continuation Phase, then any Post-treatment data will be 
assigned to the Randomized Phase.  
• 
For subjects who did enter the Continuation Phase, any Post-treatment data will be 
assigned to the Continuation Phase. 


 
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12.5. 
Appendix 5: Data Display Standards & Handling Conventions 
12.5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order [1] 
A 
DTG/ABC/3TC FDC once daily 
DTG/ABC/3TC  
1 
B 
ATV +RTV +TDF/FTC FDC once 
daily 
ATV +RTV +TDF/FTC  
2 
NOTES: 
1. 
Order represents treatments being presented in TFL, as appropriate. 
 
12.5.2. 
Baseline Definition & Derivations 
12.5.2.1. 
Baseline Definitions 
For all endpoints (unless stated otherwise) the baseline value will be the latest pre-dose 
assessment. This is generally expected to be from the Day 1 visit, although such values 
may be missing or unscheduled assessments may be performed before treatment start. 
12.5.2.2. 
Derivations and Handling of Missing Baseline Data 
Definition 
Reporting Details 
Change from Baseline 
= Post-Dose Visit Value – Baseline 
% Change from Baseline 
= 100 x [(Post-Dose Visit Value – Baseline) / Baseline] 
Maximum Change from Baseline = Calculate the change from baseline at each given timepoint  
   and determine the maximum change 
NOTES : 
• 
Unless otherwise specified, the baseline definitions specified in Section 12.5.2.1 Baseline Definitions will be used 
for derivations for endpoints / parameters and indicated on summaries and listings. 
• 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing. 
 
12.5.3. 
Reporting Process & Standards 
Reporting Process 
Software 
• The currently supported versions of SAS software and TSCG will be used. 
Reporting Area 
HARP Server 
: uk1salx00175 
HARP Area 
: \ARPROD\GSK2619619\ING117172 
QC Spreadsheet 
: \ARPROD\ GSK2619619\ING117172\(Week48 or Final)\Documents 
Analysis Datasets  
• Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.1.3 & 


 
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39 
 
Reporting Process 
AdaM IG Version 1.0. 
• For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will be 
implemented for conversion from SI to SDTM. 
Generation of RTF Files 
• RTF files will be generated for the Week 48 and end of study analyses. 
 
Reporting Standards 
General 
• The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated: 
o 4.03 to 4.23: General Principles 
o 5.01 to 5.08: Principles Related to Data Listings 
o 6.01 to 6.11: Principles Related to Summary Tables 
o 7.01 to 7.13: Principles Related to Graphics  
Formats 
• All data will be reported according to the actual treatment the subject received unless 
otherwise stated. 
• GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected. 
• Numeric data will be reported at the precision collected on the eCRF. 
• The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• Reporting for tables, figures and formal statistical analyses : 
• Actual time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• Reporting for Data Listings:  
• Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1). 
• Unscheduled or unplanned readings will be presented within the subject’s listings.  
• Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will 
be included in listings but omitted from figures, summaries and statistical analyses. 
Unscheduled Visits 
• Unscheduled visits will be assigned to a study visit using the all-inclusive windows defined in 
Section 12.3.1.  
• However, data summaries will only report visits that are planned assessment time points for 
each parameter (according to the T&E table). 
• Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points and 
in data listings, as well any algorithms that make use of additional data (e.g., SNAPSHOT). 


 
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40 
 
Reporting Standards 
Invalid Laboratory Assessments 
• Certain laboratory endpoints are required to be collected in a fasting state, i.e., glucose and 
lipids (triglycerides, total cholesterol, HDL, LDL). If these endpoints are collected in a non-
fasting state, then the results will be excluded from summaries; such results will be included in 
data listings with the fasting status noted. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• Refer to IDSL Statistical Principals 7.01 to 7.13. 
 
 
12.6. 
Appendix 6: Derived and Transformed Data 
12.6.1. 
General 
Multiple Measurements at One Time Point 
• If after window assignment there are multiple valid (see Section 12.3) assessments of a 
parameter within the same window, then the following hierarchy will be used to determine the 
value to be used for summary statistics of observed values: 
o the assessment closest to the window target Study Day; 
o if there are multiple assessments equidistant from the target Study Day, then the 
mean of these values will be used. For HIV-1 RNA, the geometric mean of the 
number of copies will be used as opposed to the arithmetic mean 
• Assessments not chosen for use in summary statistics by this algorithm will still appear in the 
associated listings. Also, such valid assessments will be used when determining values of 
potential clinical concern for the ‘any time On-treatment’ time point, and for any algorithm that 
has specific rules for which observation to use (e.g., SNAPSHOT or LOCF). 
Study Day 
• Calculated as the number of days from initial study treatment start date : 
• Ref Date = Missing                       → Study Day = Missing  
• Ref Date < Treatment Start Date   → Study Day = Ref Date –Treatment Start Date     
• Ref Data ≥ Treatment Start Date   → Study Day = Ref Date – (Treatment Start Date) + 1   
 
Note that Treatment Start Date is considered to be on Study Day 1 and the day before this is Study 
Day -1; i.e., there is no Study Day 0. 
Post-baseline 
• Post-baseline refers to the combined time periods of On-treatment and Post-treatment. Post-
baseline may be further specified according to phase of the study: Randomized or 
Continuation. 
 


 
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41 
 
12.6.2. 
Study Population 
Demographics 
Age 
• Age, in whole years, will be calculated with respect to the subject’s Screening visit.   
• GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as follows: 
o Any subject with a missing day will have this imputed as day ‘15’.  
o Any subject with a missing date and month will have this imputed as ‘30th June’. 
• Birth date will be presented in listings as ‘YYYY’. 
• Completely missing dates of birth will remain as missing, with no imputation applied. 
Consequently, the age of the subject will not be calculated and will remain missing. 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / Height (m)2 
Hepatitis Status 
• Hepatitis C status will be determined using antibody (IgM or IgG) and/or hepatitis C virus (HCV) 
RNA assessments performed during screening or during the conduct of the study.  
• If both antibody and virus RNA assessments are available, then the latter will take precedence 
and positive/negative status will be based on whether HCV RNA is detectable (i.e., ≥43 IU/mL 
[≥1.63 log IU/mL]) or not. 
• A subject will be considered positive for hepatitis B virus (HBV) if they have a positive surface 
antigen or detectable HBV DNA result during screening or during the conduct of the study. 
Framingham Risk Equation 
• The predicted probability, p, for time (t = 4,...,12 years) of coronary heart disease according to 
the Framingham equation [Anderson, 1991] is : 
(
)
u
p
e
exp
1
−
−
=
 
where 
σ
µ
−
=
)
log(t
u
 
with 
m
+
=
4181
.4
µ
 
and 
)
2784
.0
3155
.0
exp(
m
×
−
−
=
σ
 
• The quantity m is calculated as 
[
]



×
−
×
+
−
×
−
×
−
=
female
 
if
3758
.0
)
74
/
log(
8515
.1
8549
.5
male
 
if
1759
.0
)
log(
4792
.1
2
d
d
I
age
a
I
age
a
m
 
where 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
42 
 
Demographics 
(
)
LVH
s
I
HDL
TC
I
SBP
a
×
−
×
−
×
−
×
−
=
5865
.0
/
log
7181
.0
2767
.0
)
log(
9119
.0
1122
.
11
 
and 
 
with total cholesterol and HDL cholesterol measured in the same units. 
• A subject is classified as diabetic if current or past is indicated in the medical conditions eCRF 
for Type 1 or Type 2 diabetes mellitus, or if baseline fasting glucose ≥7.00 mmol/L (126 mg/dL).  
• Smoking status is collected in the eCRF on Day 1. A current smoker is defined as currently 
smoking/using tobacco or has smoked/used tobacco within the previous 6 months; a former 
smoker is defined as previously smoked/used tobacco products and has not smoked/used 
tobacco products within the previous 6 months. 
• Definite ECG for left ventricular hypertrophy (LVH) is assessed based on current or past 
indication in the medical conditions eCRF for LVH. 
• This calculation will not be performed for subjects who have indicated current or past 
myocardial infarction conditions on the eCRF. These subjects will not be included in summary 
statistics of risk, but will be counted in the highest category of risk in the summary by category. 
 
Extent of Exposure 
• Number of days of exposure to study drug will be calculated based on the formula:   
Duration of Exposure in Days = Treatment Stop Date – (Treatment Start Date) + 1 
• In the situation where IP consists of more than one drug, the earliest start date and latest stop 
date will be used.  
• Subjects who were randomized but did not report a treatment start date will be categorised as 
having zero days of exposure.  
• Missing Treatment Stop Date will be imputed, for purposes of calculating exposure, as the date 
of last visit or the recorded date of withdrawal/completion, whichever is earlier. 
• An alternative calculation of exposure will be performed where the duration of any dosing 
interruptions based on eCRF data will be subtracted from the result above. 
o The ratio (percentage) of the actual exposure to the overall exposure (i.e. study 


 
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43 
 
Extent of Exposure 
treatment stop date – study treatment start date+1) will be used to define protocol 
deviation leading to exclusion from PP Population due to study treatment 
interruption (i.e. >10%). 
o Due to local supply issues of RTV during the study, some subjects had to take 
locally prescribed RTV and this is reported on the CONEMDS eCRF rather than IP 
eCRF. When calculating interruptions, RTV records on the CONMEDS eCRF will 
be used in conjunction with the IP eCRF data.  
12.6.3. 
Safety 
ECG Parameters 
RR Interval 
• IF RR interval (msec) is not provided directly, then RR can be derived as : 
[1] If QTcB is machine read & QTcF is not provided, then : 
 
[2] If QTcF is machine read and QTcB is not provided, then:  
 
• If ECGs are manually read, the RR value preceding the measurement QT interval should be a 
collected value THEN do not derive. 
Corrected QT Intervals 
• When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and 
Fredericia’s (QTcF) formulas will be calculated, in msec, depending on the availability of other 
measurements. 
• IF RR interval (msec) is provided then missing QTcB and/or QTcF will be derived as :  
 
 
 
Adverse Events 
AE Severity – DAIDS Grading 
• The DAIDS grading for severity of clinical adverse events will be performed. 
• See protocol for DAIDS grading criteria. 
 
Laboratory Parameters 
• If a laboratory value which is expected to have a numeric value for summary purposes, has a 
non-detectable level reported in the database, where the numeric value is missing, but typically 
a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 
determine how much to add or subtract in order to impute the corresponding numeric value.  


 
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ING117172 
 
44 
 
Laboratory Parameters 
o Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
o Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1 
o Example 3: 0 Significant Digits = ‘< x’ becomes x – 1     
Glomerular Filtration Rate (GFR) 
• The Cockroft-Gault method will be used by the central laboratory to provide an estimate of 
GFR, in mL/min, as follows: 
female)
 
if
 
85
.0
(
72
CRT
weight
age)
140
(
female)
 
if
 
85
.0
(
72
CRT
88.4
weight
age)
140
(
GFR
mg/dL
mol/L
×
×
×
−
=
×
×
×
×
−
=
µ
 
where age (in years) and weight (in kg) are at time of assessment, and CRTµmol/L is 
serum creatinine concentration in GSK standard units of µmol/L. CRTmg/dL is serum 
creatinine concentration in mg/dL, and CRTµmol/L=88.4x CRTmg/dL. 
Lab Toxicities – DAIDS Grading 
• Toxicities will be based on the Division of AIDS (DAIDS) grading system, as specified in the 
protocol.  
• Toxicity grades provided by the central laboratory do not distinguish between abnormally high 
or low criteria, when both are relevant for a particular parameter. 
• When summarising toxicity grades for such parameters, they will be categorised as to whether 
they are above or below the midpoint of normal range. 
 
Parameter 
Below Midpoint 
Above Midpoint 
Fasted glucose 
Hypoglycaemia 
Hyperglycaemia 
Sodium 
Hyponatremia 
Hypernatremia 
Potassium 
Hypokalemia 
Hyperkalemia 
 
 
National Cholesterol Education Program (NCEP) Lipid Categories 
• In addition to DAIDS toxicity scales (see protocol), lipid values will be categorized according to 
the 2001 NCEP Adult Lipid Guidelines [Grundy, 2001]  
 
Parameter 
Value Range (mmol/L) 
Value Range (mg/dL) Category 
Triglycerides 
<1.70 
<150 
Normal 
1.70 to <2.26 
150 to <200 
Borderline High 
2.26 to <5.65 
200 to <500 
High 
≥5.65 
≥500 
Very High 
Total Cholesterol 
<5.18 
<200 
Desirable 
5.18 to <6.21 
200 to <240 
Borderline High 
≥6.21 
≥240 
High 
HDL Cholesterol 
<1.04 
<40 
Low 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
45 
 
Laboratory Parameters 
1.04 to <1.56 
40 to <60 
Normal 
≥1.56 
≥60 
High 
LDL Cholesterol 
<2.59 
<100 
Optimal 
2.59 to <3.37 
100 to <130 
Near/Above Optimal 
3.37 to <4.14 
130 to <160 
Borderline High 
4.14 to <4.92 
160 to <190 
High 
≥4.92 
≥190 
Very High 
Total Cholesterol / HDL Cholesterol Ratio 
• When both total cholesterol and HDL cholesterol results are available from the same date for a 
subject, then the ratio will be calculated by dividing the total cholesterol result by the HDL 
cholesterol result. The ratio can be classified as follows: 
 
Parameter 
Value Range 
Total Cholesterol 
/ HDL Ratio 
< 3.5 
3.5 to < 4.4 
4.4 to < 5 
≥ 5 
 
 
 
Other Safety Endpoints 
Columbia Suicide Severity Rating Scale (C-SSRS) 
• Missing data will not have any imputation performed. 
• Incomplete calls: 
o when no complete call is databased on the same day, the incomplete data will be 
used 
o when a complete call is databased on the same day, the data from the complete 
call will be used in the summaries. 
• Duplicate calls: 
o If they occur on the same day, the latest entry will be used. 
o If they occur on different days, take the entry closest to the target visit date.  
 
12.6.4. 
Efficacy 
HIV-1 RNA 
Snapshot (Missing, Switch or Discontinuation=Failure) 
• It is intended to be primarily a virologic assessment of the endpoint, and as such follows a 
“virology first” hierarchy. 
• Virologic Success (e.g., <50 c/mL) or Virologic Failure within an analysis window (see Section 
12.3.1) is typically determined by the last available HIV-1 RNA measurement in that window 
while the subject is On-treatment. 
• When no HIV-1 RNA data is available within a window, a subject cannot be a Virologic 


 
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46 
 
HIV-1 RNA 
Success.  Depending on the reason for lack of data, the subject will be classified as a Virologic 
Failure or reported as ‘No Virologic Data at Week X’; in the latter case, the algorithm further 
classifies the nature of the missing data. Typically, a subject withdrawn (i) due to AE or, (ii) for 
another reason yet was suppressed at the time, will be counted as ‘No Virologic Data at Week 
X’.  Should a subject withdraw for reasons other than AE and was not suppressed at the time, 
they will be a Virologic Failure. 
• For each scheduled assessment time, the snapshot response rate for a given threshold (e.g., 
<50 c/mL) is defined as: 
population
 
analysis
 
in the
 
subjects
 
of
Number 
 window
analysis
in that 
 
responders
 
of
Number 
Rate
Snapshot 
=
 
• Full details of the algorithm, including the handling of special cases, are included in Section 
12.11 
Plasma HIV-1 RNA 
• For summaries and analyses which use HIV-1 RNA level as a continuous measure, the 
logarithm to base 10 of the value will be used. 
• HIV-1 RNA results may be provided as censored values, such as <40 or >9,999,999 c/mL. For 
the purposes of summary statistics, such values will be replaced by the next value beyond the 
limit of detection, e.g., 39 or 10,000,000 c/mL, respectively, for the given examples. Data 
listings will show the censored values as provided. 
Treatment (TRDF) and Efficacy Related (ERDF) Discontinuation = Failure 
• The analysis of time to Confirmed Virologic Withdrawal or discontinuation due to treatment 
related reasons (i.e., drug-related AE, protocol defined safety stopping criteria, or lack of 
efficacy) will censor subjects who have not met CVW criteria and are ongoing in the study, or 
who have discontinued for reasons other than those related to treatment. This will be the 
Treatment Related Discontinuation = Failure (TRDF) data. 
• Subjects who have not met CVW criteria and are ongoing in the study, or who have 
discontinued for reasons other than lack of efficacy, will be censored in the analysis of the 
Efficacy Related Discontinuation = Failure (ERDF) data. 
 
 
Variance Estimator of Cochran Mantel-Haenszel Risk Difference 
 
• 
(
)
(
)
(
)
(
)
(
)2
2
ˆ
ˆ
ˆ
raˆ
v
∑
∑
∑
∑
∑
∑
+
=
+
=
k
k
k
cmh
k
k
k
k
k
cmh
cmh
W
Q
P
d
N
m
n
Q
P
d
d
  
where 
2
2
2
2
/)
(
k
k
k
k
k
k
k
k
k
k
N
n
m
m
n
x
m
y
n
P
−
+
−
=
 
2
/)
(
/)
(
k
k
k
k
k
k
k
k
k
N
x
n
y
N
y
m
x
Q
−
+
−
=
 
 


 
CONFIDENTIAL 
 
 
 
ING117172 
 
47 
 
 
 
12.6.5. 
Viral Genotyping and Phenotyping 
Genotype 
Amino Acid Changes 
• A mutation is considered present whenever the encoded amino acid residue differs from the 
amino acid that would have been encoded by the wild-type (e.g., HXB2, NL43) comparator 
gene; e.g., Q148K.  
• If the encoded amino acid is seen as a mixture of wild-type and mutant amino acid, e.g., 
Q148Q/K, the mutated amino acid is considered present at the codon of interest.  
• If the encoded amino acid is seen as a mixture of two or more amino acids, which may or may 
not include wild type, e.g., Q184K/H or Q184K/H/Q, etc., for the purposes of calculating the 
number of mutated amino acids, only one mutation is considered to be present at the codon of 
interest. 
Representation of Amino Acid Changes 
 
 
Mutations 
Amino acid change 
T69S 
Single mutation from amino acid 'T' (vendor reference) to 'S' (sample) at codon '69'  
Q148H/K/R Mixture of amino acid mutations ‘H’, ‘K’ and ‘R’ (sample) from amino acid ‘Q’ 
(vendor reference) at codon ‘148’ 
_69_1T 
First insertion of amino acid 'T' (sample) at codon '69' 
_69_2S 
Second insertion of amino acid 'S' (sample) at codon '69' 
_69_3S/A 
Third insertion of a mixture of amino acids 'S' and 'A' (sample) at codon '69' 
L74L/- 
Mixture of amino acid 'L' (sample) and a deletion at codon '74' 
V75- 
Single deletion of amino acid (sample) at codon '75' 
 
A mutation as treatment emergent in class XX, the subject must have received a drug YY in class 
XX as part of their study treatment, and the mutation must be associated with resistance to a drug in 
class XX and not present at baseline. 
  
Resistance Associated Mutations 
• Known INI mutations associated with the development of resistance to RAL, EVG or DTG: 
 
Amino Acids in 
HIV Integrase for 
Analysis 
H51Y, T66A/I/K, L74M, E92Q/V/G, Q95K, T97A, G118R, F121Y, E138A/K/D, 
G140A/C/S, Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, Q148H/K/R, 
V151I/L/A, S153F/Y, N155H/S/T, E157Q, G163R/K, S230R, R263K,  
L68V/I*, L74I*, E138T*, V151I*, G193E* 
NOTES: 
• 
Draft listing; may be modified in case of additional substantive data availability. 
• 
INI mutations listed taken from Stanford HIV Resistance Database (http://hivdb.stanford.edu/DR/cgi-
bin/rules_scores_hivdb.cgi?class=INI cited 28 Feb 2014) and accessed on 16 Feb 2015. 
• 
Each INI mutation listed had a score of ≥15. INI substitutions listed above in bold had a score of =60. 
* Denotes additional INI mutations added as they were identified during in vitro passage of DTG or seen in a 


 
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Genotype 
Amino Acid Changes 
previous DTG study in INI-experienced subjects (ING112574).  
• Major resistance mutations to other classes (i.e., NRTI, NNRTI, PI) as defined by the 
International Antiviral Society-USA (IAS-USA). The most up to date IAS-USA guidelines 
available at the time of DBF will be used in the analysis. 
Class 
Mutations 
NRTIs 
M41L, A62V, K65R/E/N, D67N, 69 insert, K70E/R, L74V, V75I, F77L, Y115F, 
F116Y, 
Q151M, M184V/I, L210W, T215Y/F, K219Q/E 
NNRTIs 
L100I, K101E/P, K103N/S, V106A/M, V108I, E138/A/G/K/Q/R, V179L, 
Y181C/I/V, Y188C/L/H, G190S/A, H221Y, P225H, F227C, M230I/L, 
PIs 
D30N,V32I , M46I/L, I47A/V, G48V, I50V/L, I54M/L, Q58E, T74P, L76V, 
V82A/T/F/L/S, N83D, I84V, N88S,L90M 
Note: List generated from IAS_USA Guideline, [Wensing, 2014] 
 
Phenotype 
Phenotypic Susceptibility 
• Phenotypic susceptibility to all licensed antiretroviral drugs and DTG will be determined using 
PhenoSense HIV assays from Monogram Inc. and will be reported as fold change (FC) in IC50 
relative to wild-type control virus NL4-3, i.e., FC of sample virus = IC50 of sample virus/IC50 of 
control virus. 
• Since the maximum assay limit for FC for each ART varies from subject to subject, FC values 
that are greater than the maximum assay limit (e.g., ‘>100’) will be interpreted as having a value 
equal to the smallest maximum assay limit for that ART in the study population for data 
analysis.  Censored values will be presented ‘as is’ in the listings. 
• Phenotypic susceptibilities will be categorised according to FC (based on Monogram 
PhenoSense assay). Clinical cut-offs (where available) or biological cut-offs by PhenoSense will 
be used to define the phenotypic susceptibility of background treatment. 
• Replication capacity is generated as part of standard phenotypic assays. 
Drug 
Abbreviation 
Class 
PhenoSense cutoff 
Abacavir 
ABC 
NRTI 
(4.5 – 6.5)a 
Lamivudine 
3TC 
NRTI 
3.5 a 
Didanosine 
ddI 
NRTI 
(1.3 – 2.2) a 
Stavudine 
d4T 
NRTI 
1.7 a 
Zidovudine 
AZT (ZDV) 
NRTI 
1.9 
Emtricitabine 
FTC 
NRTI 
3.5 
Tenofovir 
TDF 
NRTI 
(1.4 – 4) a 
Delavirdine 
DLV 
NNRTI 
6.2 
Efavirenz 
EFV 
NNRTI 
3 


 
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Phenotype 
Nevirapine 
NVP 
NNRTI 
4.5 
Etravirine 
ETR 
NNRTI 
(2.9-10) a 
Rilpivarine 
RPV 
NNRTI 
2 
Fosamprenavir/r 
FPV/r 
PI 
(4-11) a 
Atazanavir/r 
ATV/r 
PI 
5.2 a 
Indinavir/r 
IDV/r 
PI 
10 a 
Lopinavir/r 
LPV/r 
PI 
(9 – 55) a 
Nelfinavir 
NFV 
PI 
3.6 
Saquinavir/r 
SQV/r 
PI 
(2.3 – 12) a 
Tipranavir/r 
TPV/r 
PI 
(2 – 8) a 
Darunavir/r 
DRV/r 
PI 
(10 – 90) a 
Ritonavir 
RTV 
PI 
2.5 
Enfuvirtide 
T20 
FI 
6.48 
Raltegravir 
RAL 
INI 
1.5 
Elvitegravir 
EVG 
INI 
2.5  
Dolutegravir 
DTG 
INI 
(4-13) a 
a. 
clinical cutoff (lower cutoff – higher cutoff) 
 
12.6.6. 
Health outcomes 
HIVTSQs 
Treatment Satisfaction Total Score 
• Items 1 to 10 are summed to produce a score with a possible range of 0 to 60.  
• Higher scores represent greater treatment satisfaction as compared to the past few weeks. 
• A maximum of 5 items can be missing, which can be imputed to reflect the mean of the 
completed item scores. If 6 or more items are missing, then the overall treatment satisfaction 
scale score should not be computed and will remain missing. 
General Satisfaction/Clinical Sub-Score 
• Items 1, 2, 3, 9, and 10 are summed to produce a score with a possible range of 0 to 30.  
• Higher scores represent greater treatment satisfaction within this subscale as compared to the 
past few weeks. 
• These subscales can be computed if at least 4 out of 5 items are available, in which case, the 
missing item can be imputed to reflect the mean of the completed item scores. If 2 or more 
items are missing, the score should not be computed and remain missing. 
Lifestyle/Ease Sub-Score 
• Items 4, 5, 6, 7, and 8 are summed to produce a score with a possible range of 0 to 30.  
• Higher scores represent greater treatment satisfaction within this subscale as compared to the 
past few weeks. 
• These subscales can be computed if at least 4 out of 5 items are available, in which case, the 
missing item can be imputed to reflect the mean of the completed item scores. If 2 or more 
items are missing, the score should not be computed and remain missing. 
Individual Item Scores 
• Items are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, 


 
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inconvenient, inflexible, etc.).  
• Higher scores represent greater satisfaction with each aspect of treatment. 
• Missing scores will not be computed and should remain missing. 
 
SF-12 
Physical Component Score (PCS) and Mental Component Score (MCS) 
• Scores are created according to the manual [Ware, 1996] and are scored using software 
purchased from Quality Metric http://www.qualitymetric.com/. 


 
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12.7. 
Appendix 7: Premature Withdrawals & Handling of Missing 
Data 
12.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• Subject study completion (i.e. as specified in the protocol) was defined as: 
o Randomized to ATV+RTV+TDF/FTC FDC and completed the 
Randomized Phase including the Week 48 Study Visit; 
o Randomized to DTG/ABC/3TC FDC, completed the Randomized Phase 
including the Week 48 Visit, and did not enter the Continuation Phase; 
o Randomized to DTG/ABC/3TC FDC, completed the Randomized 
Phase, including the Week 48 study visit, entered and completed the 
Continuation Phase (defined as remaining on study until commercial 
supplies of DTG/ABC/3TC become locally available or development of 
DTG/ABC/3TC is terminated). 
• Withdrawn subjects were not replaced in the study. 
• All available data from subjects who were withdrawn from the study will be 
listed. 
 
12.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument : 
o These data will be indicated by the use of a “blank” in subject listing 
displays.  
o Answers such as “Not applicable” and “Not evaluable” are not 
considered to be missing data and should be displayed as such. 
• Unless stated, no imputation for missing data or premature discontinuation will 
be performed and the observed values will be used. 
Outliers 
• Any subjects excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
Health 
Outcomes 
HIV TSQ 
• For the HIV Treatment Satisfaction overall score (which is comprised of all 10 
items), a maximum of 5 items may be missed and each computed as the mean 
of the completed item scores (as discussed in [Woodcock, 2006; Woodcock, 
2001  
o If 6 or more items are missed, then the overall score should not be 
computed and instead be imputed using LOCF.  
• For the lifestyle/ease sub-score (which is comprised of 5 items), a maximum of 1 
item may be missed and computed as the mean of the completed item scores.  
o If 2 or more items are missed, then the overall score should not be 
computed and instead be imputed using LOCF.  
• For the convenience item and other individual item scores, missing scores will 
not be computed (according to Page 7 of the [HIVTSQ User Guidelines]) and 


 
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Element 
Reporting Detail 
instead be imputed using LOCF. 
12.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
Partial dates will be displayed as captured in subject listing displays. 
Exposure 
If study treatment stop date is missing, then for the purposes of calculating 
exposure, it will be imputed using the date of last visit or the recorded date of 
withdrawal/completion whichever is earlier. 
Adverse 
Events 
• The eCRF allows for the possibility of partial dates (i.e., only month and year) to 
be recorded for AE start and end dates; that is, the day of the month may be 
missing. 
• Any partial dates for adverse events will be raised to data management. 
• If the full date cannot be ascertained, the following assumptions will be made: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month, unless this is before the start date of study 
treatment; in this case the study treatment start date will be used and hence 
the event is considered On-treatment as per Appendix 4: Treatment States 
and Phases. 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month, 
unless this is after the stop date of study treatment; in this case the study 
treatment stop date will be used. 
• Completely missing start or end dates will remain missing, with no imputation 
applied. Consequently, time to onset and duration of such events will be 
missing. 
• The recorded partial date will be displayed in listings. 
Concomitant 
Medications 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
For medications recorded in the eCRF as prior ART, the earlier of this 
imputed date or the day before IP start will be used. 
• The recorded partial date will be displayed in listings. 
 


 
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12.7.2.2. 
Handling of Missing Data for Statistical Analysis 
Element 
Reporting Detail 
Snapshot 
• In the Snapshot dataset, subjects without HIV-1 RNA data in the assessment 
window for the visit of interest (due to missing data or discontinuation of IP prior 
to the visit window) are classified as non-responders in the derivation of the 
proportion of subjects with HIV-1 RNA < 50 c/mL (or <400 c/mL).  The nature of 
this missing data will be further classified in Snapshot summaries as either 
‘Virologic Failure’ or ‘No Virologic Data at Week X’; see Section 12.11 for full 
details 
LOCF 
• In the LOCF dataset, missing values will be carried forward from the previous, 
non-missing available on-treatment assessment. 
Lipid LOCF 
• If subjects initiate serum lipid-lowering agents Post-baseline, then the last 
available fasted On-treatment lipid values prior to the initiation will be used in 
place of future, observed On-treatment values.  
• Imputation will continue even if the subject discontinues the lipid-lowering agent.  
• Missing assessments will not be imputed. Subjects on lipid-lowering agents at 
baseline will be excluded from this dataset.  
• This dataset will be used for all summaries of lipids data. 
 
12.8. 
Appendix 8: Values of Potential Clinical Importance 
Element 
Reporting Detail 
Laboratory 
Values and 
Adverse 
Events 
• The DAIDS grading for severity of laboratory toxicities and clinical adverse 
events is included in the protocol.  
• The central laboratory will flag lab parameter toxicities directly in the provided 
datasets. 
ECG 
• QTc above 500 msec or change from baseline above 60 msec are 
considered to be values of potential clinical importance. 
 
12.9. 
Appendix 9: Examination of Covariates and Subgroups 
12.9.1. 
Handling of Covariates, Subgroups & Other Strata 
• 
The following is a list of covariates that may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses (See 
Section 9.1.1 for further details).  
• 
Additional covariates of clinical interest may also be considered.  
• 
If the percentage of subjects is small within a particular subgroup, then the subgroup 
categories may be refined prior to unblinding the trial.   
• 
If the category cannot be refined further, then descriptive rather than statistical 
comparisons may be performed for the particular subgroup. 


 
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Category 
Covariates and / or Subgroups 
Randomisation Strata  
Randomisation is stratified by screening plasma HIV-1 RNA and 
CD4+ cell count, although summaries and analyses will make 
use of the Baseline categories, which are considered to be 
more relevant to the analysis of the study endpoints: 
 
• Baseline plasma HIV-1 RNA (≤ vs. >100,000 c/mL) 
• Baseline CD4+ cell count (≤ vs. >350 cells/mm3). 
 
All statistical analyses will adjust for the above randomization 
strata, unless stated otherwise.  Treatment-by-Strata 
interactions will be assessed as specified in the analysis 
sections. 
 
Demographic and Baseline 
Characteristic Subgroups 
• Age: ≥50 & <50 
• Race: 
o White; Non-White 
o African American/African Heritage; Non-African 
American/African Heritage 
• Country 
• Baseline plasma HIV-1 RNA: 
o <1000; 1000 to <10,000; 10,000 to <50,000; 50,000 
to 100,000; >100,000 c/mL. 
• Baseline CD4+ cell count: 
o <50; 50 to <200; 200 to <350; 350 to <500; ≥500 
cells/mm3. 
• Baseline Centers for Disease Control and Prevention (CDC) 
category: 
o CDC Category A, 
o CDC Category B 
o CDC Category C; 
• HIV-1 Subtype: B vs non-B.  
 
 


 
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12.10. Appendix 10: Model Checking and Diagnostics for Statistical 
Analyses 
12.10.1. 
Statistical Analysis Assumptions 
Endpoint(s) 
Change from Baseline in fasted lipids (triglycerides and TC/HDL ratio) 
Analysis 
Multiple imputation 
• Model assumptions will be applied, but appropriate adjustments maybe made based on the 
data. 
• Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals (i.e. checking the normality assumption) to 
gain confidence that the model assumptions are reasonable. 
• If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data. 
• Diagnostic plots (trace and autocorrelation plots) will be checked to verify that the number of 
burn-in iterations and MCMC steps between imputed datasets are sufficient. If the trace plots 
show apparent trend or the autocorrelation plots show significant positive or negative 
autocorrelation, number of iterations will be increased until the diagnostic plots are acceptable. 
Analysis 
      MMRM 
• Model assumptions will be applied, but appropriate adjustments maybe made based on the 
data. 
• The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used. 
• An unstructured covariance structure for the R matrix will be estimated by treatment group by 
specifying ‘type=UN’ and ‘group=treat’ on the REPEATED line. 
o In the event that this model fails to converge, alternative correlation structures may be 
considered such as CSH or CS.  
o Akaike's Information Criteria (AIC) will be used to assist with the selection of 
covariance structure. 
• Distributional assumptions underlying the model used for analysis will be examined by 
obtaining a normal probability plot of the residuals and a plot of the residuals versus the fitted 
values (i.e. checking the normality assumption and constant variance assumption of the model 
respectively) to gain confidence that the model assumptions are reasonable. 
• If there are any departures from the distributional assumptions, alternative models will be 
explored using appropriate transformed data. 
 
 
 


 
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12.11. Appendix 11: Snapshot 
Detailed Algorithm Steps 
 Consider an arbitrary visit window, Week X (see Section 12.3).  
 A subject’s response (i.e., ‘Virologic Success’, ‘Virologic Failure’, or ‘No Virologic 
Data at Week X’) in that window is determined as indicated below, in the order stated. 
 
1. If non-permitted change in background ART prior to Week X: Subject = Virologic Failure. 
2. If permitted change in background ART prior to Week X AND decision to make this change 
is after the first On-treatment HIV-1 RNA result AND the latest On-treatment HIV-1 RNA 
result prior to the date of decision to switch is ≥ 50 c/mL: Subject = Virologic Failure.  
3. If non-permitted change in background ART during Week X 
OR 
if permitted change in background ART during Week X AND decision to make this 
change is after the first On-treatment HIV-1 RNA result AND the latest On-treatment 
HIV-1 RNA result prior to the date of decision to switch is >=50 c/mL  
AND:  
• no HIV-1 RNA result is available during Week X prior to change: Subject = Virologic 
Failure; 
• there is at least one HIV-1 RNA result available during Week X prior to the 
change, then consider the latest such result: 
• 
If < 50 c/mL: Subject = Virologic Success 
• 
If ≥ 50 c/mL: Subject = Virologic Failure. 
4. If there is no change in background ART prior or during Week X 
OR 
a permitted change prior or during Week X is decided on before the first On-treatment 
HIV-1 RNA result, 
OR 
a permitted change prior or during Week X is decided on after the first On-treatment 
RNA result AND the latest On-treatment HIV-1 RNA result prior to the decision to switch 
is <50 c/mL, 
AND  
at least one HIV-1 RNA result is available during Week X, then consider the latest such 
result: 
• 
If < 50 c/mL: Subject = Virologic Success; 
• 
If ≥ 50 c/mL: Subject = Virologic Failure. 
5. If there is no change in background ART prior or during Week X 
OR 
a permitted change prior or during Week X is decided on before the first On-treatment 
HIV-1 RNA result 


 
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Detailed Algorithm Steps 
OR 
a permitted change prior or during Week X is decided on after the first On-treatment 
RNA result AND the latest On-treatment HIV-1 RNA result prior to the decision to switch 
is <50 c/mL, 
AND  
no HIV-1 RNA results are available during Week X: 
• If the subject has not withdrawn from the study prior to or during Week X: Subject = 
No Virologic Data at Week X, with a reason of ‘Missing data during window but on 
study’; 
• If the subject was withdrawn from the study prior to or during Week X due to AE or 
death: Subject = No Virologic Data at Week X, with a reason of ‘Discontinued due 
to AE or Death’; 
• Otherwise, consider the subject’s last available On-treatment HIV-1 RNA result: 
 If <50 c/mL or no result is available: Subject = No Virologic Data 
at Week X, with a reason of ‘Discontinued for Other Reasons’; 
 If ≥ 50 c/mL: Subject = Virologic Failure. 
 
Examples from FDA guidance 
Data in Window 
Virologic outcome should be determined by the last available measurement while the patient is on 
treatment and continued on trial within the time window: 
• HIV-RNA = 580 copies/mL at Day 336, HIV-RNA below 50 copies/mL on Day 350. This 
should be categorized as Virologic Success. 
No Data in Window 
Discontinued study due to Adverse Event or Death: 
• Any patient who discontinues because of an AE or death before the window should be 
classified as Discontinued due to AE or Death (as appropriate), regardless of the HIV-RNA 
result, even if the HIV-RNA is below 50 copies/mL at the time of discontinuation.  
• However, if a patient has an HIV-RNA value in the time window and also discontinues in the 
time window, the viral load data should be used to classify the patient’s response. This is 
the Virology First hierarchy: 
a. HIV-RNA below 50 copies/mL at Day 336 and discontinues because of AE or even 
dies on Day 360 — this person is categorized as Virologic Success. 
b. HIV-RNA is 552 copies/mL on Day 336 and the patient discontinues on Day 360, 
the patient is categorized as Virologic Failure. 
Discontinued for Other Reasons: 
• Only patients who have achieved virologic suppression can be counted as Discontinued 
for Other Reasons. 
• If a patient discontinues the study before the window because of lack of efficacy then the 
patient should be included in the Virologic Failure row and not in the Discontinued for 


 
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Detailed Algorithm Steps 
Other Reasons row. 
• If a patient discontinues because of subject withdrew consent and his or her HIV-1 RNA 
result at the time of discontinuation was equal to or above 50 copies/mL, then he or she 
should be categorized as Virologic Failure and NOT as Discontinued for Other Reasons.  
• If a patient discontinued because of Lost to Follow-Up and the last HIV-RNA result was 49 
copies/mL, then the patient can be categorized as Discontinued for Other Reasons. 
• If patients changed background treatment — not permitted by protocol— they should be 
considered an efficacy failure and captured as Virologic Failure. 
On study but missing data in window: 
• If there are no data during Days 295 to 378, but there is an HIV-RNA below 50 copies/mL 
on Day 380, this patient should be considered On Study but Missing Data in Window. 
• If there are no data during Days 295 to 378, but there is an HIV-RNA equal to or above 50 
copies/mL on Day 280, this patient also should be classified as On Study but Missing Data 
in Window. 
Optimized Background Therapy Substitutions After Randomization 
• OBT substitutions (in-class or cross-class) permitted per protocol for documented toxicity 
reasons can be permitted on or before the first trial visit without penalty.  
If OBT substitutions for toxicity reasons occur after the first trial visit, then patients should be 
categorized as Virologic Failure if they have HIV-RNA above 50 copies/mL at the time of switch. 


 
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12.12. Appendix 12: Abbreviations & Trade Marks 
12.12.1. 
Abbreviations 
Abbreviation 
Description 
ABC 
Abacavir 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
ART 
Antiretroviral Treatment 
ATC 
Anatomical Therapeutic Chemical 
ATV 
Atazanavir 
c/ml 
Copies per milliliter 
CDC 
Centers for Disease Control and Prevention 
CDISC 
Clinical Data Interchange Standards Consortium 
CD4+ 
Helper-inducer T-lymphocyte having surface antigen CD4 (cluster of 
differentiation 4) 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
CRT 
Serum creatinine 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CV 
Cardiovascular 
DAIDS 
Division of AIDS 
DP 
Decimal Places 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Record Form 
ERDF 
Efficacy Related Discontinuation = Failure 
FC 
Fold change 
FDA 
Food and Drug Agency 
FDC 
Fixed Dose Combination 
FU 
Follow-up 
GFR 
Glomerular Filtration Rate 
GSK 
GlaxoSmithKline 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HDL 
High density lipoprotein 
HIV(-1) 
Human immunodeficiency virus (type 1) 
HIVTSQs 
HIV Treatment Satisfaction Questionnaire  
HSR 
Hypersensitivity reaction 
IAS-USA 
International Antiviral Society-USA 
ICH 
International Conference on Harmonisation 
IDSL 
Integrated Data Standards Library 
IG 
Implementation Guide 
IN(I) 
Integrase (Inhibitor) 
IP 
Investigational Product 


 
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Abbreviation 
Description 
ITT(E) 
Intent-To-Treat (Exposed) 
LDL 
Low density lipoprotein 
LOCF 
Last Observation Carries Forward 
LVH 
left ventricular hypertrophy 
MAR 
Missing at random 
MCMC 
Markov Chain Monte Carlo 
MCS 
Mental Component Score 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
MMRM 
Mixed Model Repeated Measures 
NCEP 
National Cholesterol Education Program 
NNRTI 
Non-nucleoside Reverse Transcript Inhibitor 
NRTI 
Nucleoside Reverse Transcript Inhibitor 
OC 
Observed Case 
PCS 
Physical Component Score 
PDMP 
Protocol Deviation Management Plan 
PI 
Protease Inhibitor 
PP 
Per Protocol 
PSRAE 
Possibly suicidality related Adverse Event 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
RNA 
Ribonucleic acid 
RTF 
Rich text format 
RTV 
Ritonavir 
RUCAM 
Roussel Uclaf Causality Assessment Method 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis Software 
SBP 
Systolic blood pressure 
SDTM 
Study Data Tabulation Model 
SF-12 
12-Item Short Form  
SOC 
System Organ Class 
TC 
Total Cholesterol 
TDF/FTC 
Tenofovir/emtricitabine 
TFL 
Tables, Figures & Listings  
TRDF 
Treatment Related Discontinuation = Failure 
VF 
Virologic Failure 
 


 
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12.12.2. Trademarks 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
Dolutegravir 
 
Norvir 
Epzicom/Kivexa 
 
Reyataz  
 
 
SAS 
 
 
Truvada 
 
 
TSCG 
 
 
TYLENOL 
 
 
12.13. Appendix 13: Final (End of Study) Analysis 
This appendix provides the details of the planned analyses and data displays for 
ING117172 End of Study (EoS) reporting. 
   
The primary analysis (i.e. interim analysis at Week 48) was completed based on the 
original RAP.  This appendix is written to cover only analyses included in the final end of 
study reporting. All derivations described in the study analysis plan will be re-used for 
end of study reporting and only those definitions and derivations that have changed since 
the previous interim analysis are described below. This additional appendix summarizes 
only the key endpoints of interest for the final analysis and explain any deviations from 
the primary analysis. The details of the final EOS reporting and analysis plan are 
described below: 
 
1. The analysis for which the data have not been changed since last interim analysis 
will not be reported to avoid redundancy. These reports include the analyses of 
demographic and baseline characteristics. 
2. No subgroup analysis, hypotheses testing, or statistical analyses will be 
performed. 
3. All required disclosure outputs following the FDAAA and EudraCT 
guidelines will be produced.  
4. For the purpose of creation of Mexico Final Safety Report and submission to 
Ministry of Health, some listings at Mexico sites will be reported separately. Such 
listings are identified in the Programming notes in Section 12.13.8. These listings 
will include data from both Randomized and Continuation Phase. 
5. All by visit tables will have all visits reported from both Randomized and 
Continuation Phase. 
6. All listings that include both Randomized and Continuation Phase data will have 
the Phase mentioned in the outputs except for Listing of Investigational Product 
Exposure Data. 
 
 


 
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12.13.1. 
Study Phases 
In previous analysis (primary Week 48 reporting), data were summarized only for the 
Randomized phase of the study. However, when data from the Continuation phase were 
available, certain displays were repeated for the combined time period of Randomized 
plus Continuation phases. For EoS reporting, if for any display, data from both study 
phases (Randomized phase plus Continuation phase) are included, they will be tabulated 
in one summary table, unless specified otherwise, and it will be noted in the title of the 
output. For listings that contain all the data, a new column will be added to specify the 
phase of the study for each record.   
 
Start and end date for Randomized and open-label phases are defined as follows: 
Study Treatment Date 
Definition 
Randomized phase treatment start 
date 
The earliest exposure start date, where investigational 
product is either 
DTG/ABC/3TC or ATV+RTV+TDF/FTC  
Randomized phase treatment end 
date 
• If Treatment arm= ATV+RTV+TDF/FTC  
 Randomized phase treatment end date= 
Last non-missing exposure date. 
• If Treatment arm= DTG/ABC/3TC 
 Randomized phase treatment end date= 
Week 48 visit date or unscheduled Week 
48 visit date. 
 If the participant discontinued the study 
before Week 48, then Randomized phase 
treatment end date= Last non-missing 
exposure end date  
Continuation phase treatment start 
date 
• Randomization phase treatment end date+1 day 
where Treatment arm = DTG/ABC/3TC 
• There will be no Continuation phase if 
Treatment arm= ATV+RTV+TDF/FTC.  
Continuation phase treatment end 
date 
• The last non-missing exposure end date after 
entering the Continuation Phase in the 
DTG/ABC/3TC arm. 
 
 


 
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12.13.1.1. Study Phases for all events that do not have visits associated with 
them 
• 
Note: In the case of a completely missing start date, the event will be considered to have started in the 
Randomized Phase.  
12.13.1.2. Treatment Phases for Concomitant/Post-Therapy Medications Data 
• 
For subjects who do not enter into Continuation phase, all on-treatment and post-
treatment concomitant medications (conmeds) will be in Randomized phase; 
• For subjects who enter into Continuation phase; all on-treatment and post-treatment 
conmeds will be in Randomized phase, Continuation phase or both (Randomized + 
Continuation) phases depending on the conmeds start/stop dates.  
o Randomized phase- If the conmeds end dates <Continuation treatment start 
date.  
o Continuation phase- If the conmeds start dates ≥Continuation treatment start 
date. 
o Randomized and Continuation- 
 If conmed start date< Continuation treatment start date + conmed end 
date≥ Continuation treatment start date 
 If conmed start date< Continuation treatment start date + conmed end 
date= missing 
 If conmed start date= missing + conmed end date≥ Continuation 
treatment start date 
 If conmed start date= missing + conmed end date= missing 
12.13.2. Analysis Populations for the Continuation Phase  
The following populations have been defined only for the Continuation Phase. For all 
other populations refer to Section 5. 
Population  
Definition/ Criteria.  
Analysis Evaluated  
Safety- Continuation Phase 
 
Comprises of all subjects in 
the DTG/ABC/3TC arm who 
receive at least one dose of 
study treatment after entering 
the Continuation Phase.  
• 
Safety  
Phase  
Definition  
Randomized Phase Event 
Randomized phase treatment start date ≤ Event Start Date 
≤Randomized phase end date 
 
Continuation Phase Event 
Event Start Date ≥ Continuation phase treatment start date 


 
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Population  
Definition/ Criteria.  
Analysis Evaluated  
ITT-E- Continuation Phase 
Comprises of all subjects in 
the ITT-E population (as 
defined in Section 5) in the 
DTG/ABC/3TC arm who 
enter the Continuation Phase  
• 
Study Population 
 
12.13.3. 
Study Population  
The study population summaries and data listings will be based on the ITT-E or ITT-E- 
Continuation Phase population, unless otherwise specified. Subject accountability 
summary will be produced for the overall study and separately for the Continuation 
Phase. Overview of the key planned study population endpoints:  
• Study Populations  
• Subject Accountability  
• Concomitant and Antiretroviral Medications 
• Protocol deviations 
12.13.4. 
Safety Analysis 
All safety displays will be based on the Safety population or Safety- Continuation Phase 
Population. The core adverse event displays for the final report have been identified 
based on the IDSL library required tables. For AE data (including COVID-19), unless 
stated otherwise, the summaries and listings will include only those AEs that occurred 
during Continuation Phase.  
Summaries of AE required for the FDAAA and EudraCT will be generated in this 
reporting effort. Such summaries are identified in the Programming notes. These 
summaries will include participants from both Randomized and Continuation Phase.  
Common AEs are those with >=3% (without rounding) incidence for any treatment.  
One figure will be reported to present Maximum ALT vs. Maximum Total Bilirubin. 
Overview of the key planned safety endpoints: 
• Extent of Exposure 
• Adverse Events 
• Maximum Post-Baseline Emergent Clinical Chemistry/ Haematology Toxicities/ 
Hepatobiliary Laboratory Abnormality Criteria  
• Liver Events Assessment 
• Positive Suicidal indication Alerts based on eC-SSRS will be listed including data 
only in the Continuation Phase 
• For subjects at Mexico sites and non-Mexico sites the following listings will be 
generated in this reporting effort. These listings will include data from both 
Randomized and Continuation Phase.  
 Listing of Non-Serious AEs of Subjects at Mexico sites  
 Listing of SAEs of Subjects at Mexico sites 


 
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 Listing of SAEs of Subjects at non-Mexico sites 
 
12.13.5. 
Efficacy Analysis 
The efficacy summaries and data listings will be based on the ITT-E population, unless 
otherwise specified. Subjects Randomized to the ATV+RTV+TDF/FTC arm completed 
the study after the Week 48 visit. Thus, the Snapshot algorithm that was used in the 
previous interim analyses would not be appropriate. Instead, HIV-1 RNA viral load will 
be summarized using observed data (i.e., subjects with missing data at a time point are 
excluded). The summaries and listings will be based on both Randomized and 
Continuation phase.  Overview of the key planned efficacy endpoints:  
• Absolute values in Plasma HIV-1 RNA and CD4+ Cell counts over time 
• Proportion of Subjects with Plasma HIV-1 RNA < 50 c/ mL– observed data  
• Proportion of subjects with Confirmed Virologic Withdrawal based on observed 
data.  
• Change from Baseline in CD4+ cell count (cells/mm3) and Plasma HIV-1 RNA 
(log10 c/mL) by Visit 
• Incidence of disease progression and HIV- associated conditions 
 
 
12.13.6. 
Virology Analysis 
The Virology displays will be based on ITT-E or Viral Genotypic and Viral 
Phenotypic populations. All virology summaries and Listings will include subjects who 
met Confirmed Virologic Withdrawal criteria during both Randomized and Continuation 
phase by separating the phases by page. Resistance testing will be performed on subjects 
at non-CVW time (ie, last on-treatment VL>400), and these subjects’ viral data will be 
included only in the listing of resistance data for subjects at non-CVW time.  
 
  
Prespecified lists of integrase substitutions have been modified since the previous interim 
analysis, hence an updated list of known INSTI mutations has been added in Table 8 and 
IAS-USA major resistance associated mutations (RAMs) to other classes (i.e., NRTI, 
NNRTI, PI) are listed in Table 9.  


 
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12.13.6.1. Genotype 
Table 8 
Known INSTI mutations associated with the development of 
resistance to RAL, EVG or DTG  
Amino Acids 
in HIV 
Integrase for 
Analysis 
H51Y, T66A/I/K, L74M, E92Q/V/G, Q95K, T97A, G118R, F121Y, E138A/K, 
G140A/C/S, Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, Q148N/H/K/R, 
V151I/L/A, S153F/Y, N155H/S/T, E157Q, G163R/K, S230R, R263K, 
L68V/I*, L74I*, E138T*, G193E* 
NOTES:   
• 
Current listing includes INSTI mutations identified via the Stanford HIV Resistance database, or 
identified during in vitro passage of DTG, or as seen in a previous DTG studies in INSTI-
experienced subjects (i.e. ING112574) and may be modified in case of additional substantive data 
availability.  
• 
INSTI mutations in bold have the maximum score of 60 and are for any INSTI drug in the 
Stanford database v8.9 (http://hivdb.stanford.edu/DR/cgi-bin/rules_scores_hivdb.cgi?class=INSTI 
last updated on 25 OCT 2019 and accessed on 17 FEB 2020); the rest have a maximum score <60.  
• 
The INSTI mutations listed are historically identified via the Stanford HIV Resistance database, 
and also include mutations identified during in vitro passage of DTG, or as seen in a previous 
DTG study in INSTI-experienced subjects (ING112574).  
 
 
Table 9 
Major resistance mutations to other classes (i.e., NRTI, NNRTI, PI) as 
defined by the International Antiviral Society-USA (IAS-USA).  
Class 
Mutations 
NRTIs 
M41L, K65R/E/N, D67N, 69 insert, K70E/R, L74V, Y115F, M184V/I, 
L210W, T215Y/F, K219Q/E; [A62V, V75I, F77L, F116Y, Q151M] 
NNRTIs 
L100I, K101E/P, K103N/S, V106A/M, V108I, E138A/G/K/Q/R, 
V179L,Y181C/I/V, Y188C/L/H, G190S/A, H221Y, P225H, F227C, 
M230I/L 
PIs 
D30N,V32I , M46I/L, I47A/V, G48V, I50V/L, I54V/M/L, Q58E, T74P, 
L76V, V82A/T/F/L/S, N83D, I84V, N88S, L90M 
NOTES:   
• 
Updated to “2019 Resistance Mutations Update Volume 27 Issue 3, July/August 2019 
• 
The most up to date IAS-USA guidelines available at the time of DBF will be used in the analysis. 
• 
Q151M Complex: Q151M usually occurs in combination with two or more of the following four 
accessory NRTI mutations A62V, V75I, F77L, and F116Y. However, if any one of these 
mutations occur alone, they shall be considered as major mutation for the NRTI class.  
 
 


 
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A mutation as treatment emergent in class XX, the subject must have received a drug YY 
in class XX as part of their study treatment, and the mutation must be associated with 
resistance to a drug in class XX and not present at baseline. 
 
Stanford Genotypic Susceptibility Score (GSS) 
• To establish genotypic susceptibility to ART treatment, a genotypic sensitivity score will be 
calculated. 
• Genotypic sensitivity to each drug will be assessed using the HIVdb, the Integrated Genotypic 
Resistance Interpretation System [Liu, 2006]. 
• In the HIVdb system, each HIV-1 drug resistance mutation is assigned a drug penalty score. 
The penalty scores for each drug resistance mutation are available at 
NNRTI: https://hivdb.stanford.edu/dr-summary/mut-scores/NNRTI/ 
NRTI:  https://hivdb.stanford.edu/dr-summary/mut-scores/NRTI/ 
PI:  https://hivdb.stanford.edu/dr-summary/mut-scores/PI/ 
INSTI:   https://hivdb.stanford.edu/dr-summary/mut-scores/INSTI/. Scores for particular 
patterns of INSTIs are also available at https://hivdb.stanford.edu/dr-summary/pattern-
scores/INSTI/ 
The drug resistance estimate is obtained by adding together the penalty scores from all 
mutations associated with resistance to that drug and then a numeric score (GSS) is 
applied for each drug as shown below. The sum scores are titrated to fall within the 
following ranges susceptible, potential low-level resistance, low-level resistance, 
intermediate resistance, and high-level resistance (see table below). 
Resistance 
Estimate 
S-GSS Score 
Sensitivity 
0 – 9 
1 
Susceptible 
10 – 14 
0.75 
Potential low-level resistance 
15 – 29 
0.5 
Low-level resistance 
30 – 59 
0.25 
Intermediate resistance 
≥60 
0 
High-level resistance 
 
The HIVdb GSS will then be calculated for each subject defined as the sum of the 
resistance scores for each component of their drugs. 
12.13.6.2. Phenotype 
To establish susceptibility to background treatment, a phenotypic sensitivity score will be 
calculated. Phenotypic susceptibility to each drug in a subject’s background regimen will 
be determined by applying drug-associated cutoffs as defined by the PhenoSense 
algorithm to the phenotypic fold resistance to that drug at a certain timepoint (e.g., 
Screening or Baseline). A numeric score will be assigned to each background drug using 
two different methods: one with full sensitivity only (PSSf) and one with partial 
sensitivity included (PSSp). 
 
 


 
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PSS with Full Sensitivity Only (PSSf) 
Fold Change 
Score 
Interpretation 
> clinical lower cutoff or biologic cutoff 
0 
resistance 
≤ clinical lower cutoff or biologic cutoff 
1 
sensitive 
 
PSS with Partial Sensitivity Included (PSSp) 
Fold Change 
Score 
Interpretation 
> clinical higher cutoff 
0 
resistance 
≤ clinical higher cutoff and > clinical lower cutoff 
0.5 
partially sensitive 
≤ clinical lower cutoff 
1 
sensitive 
 
Both PSSf and PSSp will be calculated separately for each subject defined as the sum of the 
resistance scores for each background drug. 
 
Clinical and Biological Cutoff Values for the PhenoSense HIV Drug Resistance Assay 
have changed since the previous interim analysis, hence for EoS phenotypic susceptibility 
will be categorised according to Fold Change as shown in Table 10 (based on Monogram 
PhenoSense assay). 
 


 
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Table 10 
Clinical and Biological Cutoff Values for the PhenoSense HIV Drug 
Resistance Assay 
Drug 
Abbreviation 
Class 
PhenoSense Cutoff 
Abacavir 
ABC 
NRTI 
(4.5 – 6.5)a 
Lamivudine 
3TC 
NRTI 
3.5 a 
Didanosine 
ddI 
NRTI 
(1.3 – 2.2) a 
Stavudine 
d4T 
NRTI 
1.7 a 
Zidovudine 
AZT (ZDV) 
NRTI 
1.9 
Emtricitabine 
FTC 
NRTI 
3.5 
Tenofovir 
TDF 
NRTI 
(1.4 – 4) a 
Delavirdine 
DLV 
NNRTI 
6.2 
Efavirenz 
EFV 
NNRTI 
3 
Nevirapine 
NVP 
NNRTI 
4.5 
Etravirine 
ETR 
NNRTI 
(2.9-10) a 
Rilpivirine 
RPV 
NNRTI 
2.5 
Fosamprenavir 
FPV 
PI 
2 a,c 
Fosamprenavir/r 
FPV/r 
PI 
(4-11) a 
Atazanavir 
ATV 
PI 
2.2 a, 
Atazanavir/r 
ATV/r 
PI 
5.2 a,c 
Indinavir/r 
IDV/r 
PI 
10 a 
Lopinavir/r 
LPV/r 
PI 
(9 – 55) a 
Nelfinavir 
NFV 
PI 
3.6 
Saquinavir 
SQV 
PI 
1.7 a,c 
Saquinavir/r 
SQV/r 
PI 
(2.3 – 12) a 
Tipranavir/r 
TPV/r 
PI 
(2 – 8) a 
Darunavir/r 
DRV/r 
PI 
(10 – 90) a 
Ritonavir 
RTV 
PI 
2.5 
Enfuvirtide 
T20 
FI 
6.48b 
Raltegravir 
RAL 
INSTI 
1.5 
Elvitegravir 
EVG 
INSTI 
2.5  
Dolutegravir 
DTG 
INSTI 
(4-13) a 
a: clinical cutoff (lower cutoff – higher cutoff) 
b: standard cut-off used by Monogram Inc. until clinical or biological cutoff have been determined  
c: Only the boosted cutoff shall be used to compute the PhenoSense sensitivity for Atazanavir, 
Fosamprenavir and Saquinavir except stated otherwise. 
 
a.  
Overview of the key planned virology endpoints:  
• Genotypic and Phenotypic Accountability  
• Major Mutations in NNRTI, NRTI and PI Classes and Pre-specified Mutations in 
INSTI from Baseline to Time of CVW 
• Fold Change Summary of Fold Change to DTG at Baseline and Time of CVW  
 


 
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12.13.7. 
COVID-19 Analysis 
This study started in 2013 and is being continued during the outbreak of the 
ongoing COVID -19 pandemic. The information regarding the number of 
subjects affected by COVID-19 and its symptoms will be reported according to 
GSK core standards. The visits impacted due to the pandemic outbreak will be 
reported. Protocol deviations or adverse events related to COVID-19 if any, will 
also be reported according to GSK core standards.    
 
12.13.8. 
List of Data Displays for Final (End of Study) 
Study Population Tables 
No. 
Population 
IDSL / 
TST ID / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
1.1 
All 
Subjects 
Screened  
SA1 
Summary of Study Populations 
CS CORE; 
Only add the 
populations that 
will be used for 
EOS 
EOS 
1.7 
ITT(E) -
Continuation 
Phase 
DV1a 
Summary of Important Protocol 
Deviations by relationship to 
COVID-19 Pandemic- 
Continuation Phase 
CS CORE 
EOS 


 
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Study Population Tables 
No. 
Population 
IDSL / 
TST ID / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
1.27 
ITT(E) -
Continuation 
Phase 
Same as 
Week 48 
Table 
1.27 
Summary of Subjects by Country 
and Investigator- Continuation 
Phase 
 
EOS 
1.28 
   ITT(E) 
ES1 
Summary of Subject Status and 
Subject Disposition by 
Relationship to COVID-19 
Pandemic  
FDAAA, 
EudraCT 
For overall, both 
phases 
Summarise by: i) 
Overall ii) 
Related to 
COVID-19, ii) Not 
related to 
COVID-19 
EOS 
1.29 
ITT(E) -
Continuation 
Phase 
ES1 
Summary of Subject Status and 
Subject Disposition by 
relationship to COVID-19 
Pandemic- Continuation Phase 
New Output; 
FDAAA, 
EudraCT 
Summarise by: i) 
Overall ii) 
Related to 
COVID-19, ii) Not 
related to 
COVID-19 
EOS 
 


 
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Efficacy Tables  
No.  Population 
IDSL / TST ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
2.7 
ITT(E) 
Same shell as ARIA Week 
48 Table 2.7 
Summary of Change 
from Baseline in 
Plasma HIV-1 RNA 
(log10 c/mL) by Visit 
 
EOS 
2.13 
ITT(E) 
Same shell as ARIA Week 
48 Table 2.13 
Proportion of Subjects 
Meeting Confirmed 
Virologic Withdrawal 
Criteria by Visit- 
Observed Case 
 
EOS 
2.15 
ITT(E) 
Same shell as ARIA Week 
48 Table 2.15 
Summary of Change 
from Baseline in CD4+ 
Cell Count 
(cells/mm^3) by Visit 
 
EOS 
2.16 
ITT(E) 
HIV1 
Summary of Post-
Baseline HIV-1 
Associated Conditions 
Including Recurrences 
 
EOS 
2.17 
ITT(E) 
HIV1 
Summary of Post-
Baseline HIV-1 
Associated Conditions 
Excluding 
Recurrences 
 
EOS 
2.18 
ITT(E) 
HIV2 
Summary of Post-
Baseline HIV-1 
Disease Progressions 
 
EOS 
2.19 
ITT(E) 
gsk2619619/mid200336/ 
final_01/table 2.1 
Proportion of Subjects 
with Plasma HIV-1 
RNA <50 c/mL by Visit 
– Observed Case 
 
EOS 
2.20 
ITT(E) 
gsk2619619/mid200336/ 
final_01/table 2.41 
Summary of Absolute 
values in plasma HIV-
1 RNA over time 
 
EOS 
2.21 
ITT(E) 
gsk2619619/mid200336/ 
final_01/table 2.41 
Summary of CD4+ cell 
counts over time 
 
EOS 
 


 
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Efficacy Figures 
No. 
Population 
IDSL / 
TST ID / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
2.4 
ITT(E) 
Same 
shell as 
Gemini 
Figure 
2.3 
Individual Plasma HIV-1 RNA 
(log10 c/mL) and CD4+ Profiles 
by Visit for Subjects with at least 
One Suspected Virologic 
Withdrawal Visit 
 
EOS 
 


 
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Safety Tables 
No 
Population 
IDSL / 
TST ID / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
3.2 
Safety 
Same 
shell as 
Week 48 
table 3.1 
Summary of Extent of 
Exposure to Investigational 
Product  
CS Core 
 
EOS 
3.52 
Safety- 
Continuation 
Phase 
Same 
shell as 
Week 48 
table 3.1 
Summary of Extent of 
Exposure to Investigational 
Product – Continuation Phase 
New output 
EOS 
3.3 
Safety-
Continuation 
Phase 
AE5 
Summary of All Adverse 
Events by System Organ Class 
and Maximum Toxicity- 
Continuation Phase 
CS Core 
 
EOS 
3.4 
Safety-
Continuation 
Phase 
AE3 
Summary of Common (>=3%) 
Adverse Events by Overall 
Frequency- Continuation 
Phase 
CS Core 
 
EOS 
3.5 
Safety-
Continuation 
Phase 
AE3 
Summary of Common (>=3%) 
Grade 2-4 Adverse Events by 
Overall Frequency- 
Continuation Phase 
CS Core 
 
EOS 
3.6 
Safety-
Continuation 
Phase 
AE5 
Summary of All Drug-Related 
Adverse Events by System 
Organ Class and Maximum 
Toxicity- Continuation Phase  
CS Core 
 
EOS 
3.7 
Safety-
Continuation 
Phase 
AE3 
Summary of Common (>=3%) 
Drug-Related Grade 2-4 
Adverse Events by Overall 
Frequency- Continuation 
Phase 
CS Core 
 
EOS 
3.8 
Safety-
Continuation 
Phase 
AE16 
Summary of Serious Adverse 
Events by System Organ 
Class- Continuation Phase 
 
EOS 


 
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3.9 
Safety 
AE16 
Summary of Serious Adverse 
Events by System Organ Class 
and Preferred Term (Number 
of Subjects and Occurrences)  
CS Core 
 
New output.  
FDAAA, 
EudraCT 
 
EOS 
3.11 
Safety-
Continuation 
Phase 
AE1 
Summary of Adverse Events 
Leading to 
Withdrawal/Permanent 
Discontinuation of 
Investigational Product –
Continuation Phase 
CS Core 
 
EOS 
3.13 
Safety 
AE3 
Summary of Common (>=3%) 
Non-Serious Adverse Events 
CS Core 
FDAAA 
 
 
 
EOS 
3.14 
Safety 
AE15 
Summary of Common (>=3%) 
Non-Serious Adverse Events 
by System Organ Class and 
Preferred term (Number of 
Subjects and Occurrences) 
CS Core 
EudraCT  
 
 
 
EOS 
3.29 
Safety-
Continuation 
Phase 
Same 
shell as 
Week 48 
Table 
3.29 
Summary of Maximum Post-
Baseline Emergent Chemistry 
Toxicities –Continuation Phase 
CS Core 
 
EOS 
3.30 
Safety-
Continuation 
Phase 
Same 
shell as 
Week 48 
Table 
3.30 
Summary of Maximum Post-
Baseline Emergent 
Hematology Toxicities –
Continuation Phase 
CS Core 
 
EOS 
3.41 
Safety-
Continuation 
Phase 
LIVER10 Summary of Subjects Meeting 
Hepatobiliary Laboratory 
Abnormality Criteria Post-
Baseline Emergent- 
Continuation Phase 
 
 
EOS 
3.42 
Safety-
Continuation 
Phase 
Same 
shell as 
ARIA 
Week 48 
Subjects Meeting Hepatobiliary 
Abnormality Criteria - Post-
Baseline Emergent- 
Continuation Phase 
 
EOS 


 
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3.50 
Safety-
Continuation 
Phase 
PAN1 
Summary of COVID-19 
Assessment for Subjects with 
COVID-19 Adverse Events- 
Continuation Phase 
New Output 
EOS 
3.51 
Safety-
Continuation 
Phase 
PAN3 
Summary of COVID-19 
Symptoms for Subjects with 
COVID-19 Adverse Events- 
Continuation Phase 
New Output 
EOS 
 
Safety Figures 
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
3.3 
Safety-
Continuation 
Phase 
LIVER9 
Scatter Plot of Maximum ALT 
vs. Maximum Total Bilirubin-
Continuation Phase- 
Continuation Phase 
CS CORE 
 
EOS 
3.10 
Safety 
gsk1349572/ 
ing111762/ 
final_01/ 
Figure 8.27 
Plot of cumulative exposure 
to Investigational Product  
New output;  
 
EOS 
 


 
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Virology Tables 
No. 
Populatio
n 
IDSL / TST ID / Example Shell 
Title  
Programmin
g Notes 
Deliverabl
e  
7.9 
Genotypic 
PFG1 
Summary of 
Major 
Mutations in 
NNRTI, NRTI 
and PI 
Classes and 
Pre-specified 
Mutations in 
INSTI Class 
at Baseline 
and time of 
CVW for 
Subjects 
Meeting 
CVW Criteria 
New Output; 
 
For EoS 
both phases 
will be 
included. 
EOS 
7.1
0 
Genotypic gsk1349572/mid200304/primary_0
1/ Table 12.1 
Summary of 
Subject 
Accountabilit
y: Genotypes 
Available  
New Output; 
 
For EoS 
both phases 
will be 
included. 
EOS 
7.5 
Phenotypi
c 
Same shell as Week 48 Table 7.5 
Summary of 
Phenotype at 
time of CVW 
by 
phenotypic 
cut-off 
For EoS 
both phases 
will be 
included 
EOS 
7.7 
Phenotypi
c 
Same shell as Week 48 Table 7.7 
Summary of 
Fold Change 
at Baseline 
and Time of 
CVW 
For EoS 
both phases 
will be 
included. 
EOS 
7.1
1 
Phenotypi
c 
gsk1349572/mid200304/primary_0
1/ Table 12.6 
Summary of 
Subject 
Accountabilit
y: 
Phenotypes 
Available 
New Output; 
 
For EoS 
both phases 
will be 
included. 
EOS 
 


 
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ICH Listings 
No
. 
Populatio
n 
IDSL / 
TST ID / 
Exampl
e Shell 
Title  
Programming Notes 
Deliverabl
e  
4 
ITT-E 
ES2 
Listing of Reasons 
for Study Withdrawal 
CS CORE 
 
 
EOS 
6 
ITT-E-
Continuatio
n Phase 
DV2 
Listing of Important 
Protocol Deviations -
Continuation Phase 
CS CORE 
 
EOS 
79 
ITT-E-
Continuatio
n Phase 
DV2 
Listing of All Non-
Important COVID-19 
related Protocol 
Deviations- 
Continuation Phase 
New Output 
EOS 
10 
ITT-E 
Same as 
Week 48 
listing 10 
Listing of 
Quantitative Plasma 
HIV-1 RNA Data 
 
EOS 
13 
Safety 
HIV_IP
5 
Listing of 
Investigational 
Product Exposure 
Data 
CS CORE 
 
 
EOS 
16 
Safety-
Continuatio
n Phase 
AE8 
Listing of All 
Adverse Events-
Continuation Phase 
CS CORE 
 
EOS 
17 
Safety-
Continuatio
n Phase 
AE8 
Listing of Fatal 
Adverse Events-
Continuation Phase 
CS CORE 
 
EOS 
18 
Safety-
Continuatio
n Phase 
AE8 
Listing of Non-Fatal 
Serious Adverse 
Events-Continuation 
Phase 
CS CORE 
 
EOS 
19 
Safety-
Continuatio
n Phase 
AE8 
Listing of Adverse 
Events Leading to 
Withdrawal/Permane
nt Discontinuation of 
Investigational 
Product-
Continuation Phase 
CS CORE 
 
EOS 


 
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ICH Listings 
No
. 
Populatio
n 
IDSL / 
TST ID / 
Exampl
e Shell 
Title  
Programming Notes 
Deliverabl
e  
20 
Safety-
Continuatio
n Phase 
AE2 
Listing of 
Relationship of 
Adverse Event 
System Organ 
Classes, Preferred 
Terms, and 
Verbatim Text-
Continuation Phase 
CS CORE 
 
EOS 
22 
Safety 
LB5 
Listing of Laboratory 
Data for Subjects 
with Grade 3 or 4 
Post-Baseline 
Emergent Toxicities- 
Continuation Phase 
CS CORE 
 
Use the shell of Listing 56 from 
gsk1349572/mid200304/primary_
01/ 
 
EOS 
25 
Safety-
Continuatio
n Phase 
PSRAE
1 
Listing of Possible 
Suicidality-Related 
Adverse Event Data: 
Event and 
Description (Section 
1- Section 2) -
Continuation Phase 
 
EOS 
26 
Safety-
Continuatio
n Phase 
PSRAE
3 
Listing of Possible 
Suicidality-Related 
Adverse Event Data: 
Possible Cause(s) 
(Section 3)- 
Continuation Phase 
 
EOS 
27 
Safety-
Continuatio
n Phase 
PSRAE
4 
Listing of Possible 
Suicidality-Related 
Adverse Event Data 
(Section 4)- 
Continuation Phase 
 
EOS 
28 
Safety-
Continuatio
n Phase 
PSRAE
5 
Listing of Possible 
Suicidality-Related 
Adverse Event Data 
(Section 5- Section 
8)- Continuation 
Phase 
 
 EOS 
 


 
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Non-ICH Listings 
No. 
Population 
IDSL / TST ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
29 
All 
Subjects 
Screened 
Same shell as ARIA Week 
48 Listing 29 
Listing of Study 
Populations 
 
EOS 
32 
ITT-E 
Same shell as ARIA Week 
48 Listing 32 
Listing of Visit 
Dates 
 
EOS 
40 
ITT-E 
Same shell as ARIA Week 
48 Listing 40 
Listing of 
Investigational 
Product 
Accountability  
 
EOS 
41 
ITT-E-
Continuation 
Phase 
CM2 
Listing of 
Concomitant 
Medications- 
Continuation 
Phase 
CS CORE 
 
EOS 
45 
ITT-E-
Continuation 
Phase 
CM2 
Listing of 
Concomitant 
ART 
Medications- 
Continuation 
Phase 
 
EOS 
48 
ITT-E 
Same shell as ARIA Week 
48 Listing 48 
Listing of 
Subjects with 
Confirmed 
Virologic 
Withdrawal 
Data in both 
Phases will be 
included 
EOS 
49 
ITT-E 
Same shell as ARIA Week 
48 Listing 49 
Listing of CD4+ 
Cell Count Data 
Data in both 
Phases will be 
included 
EOS 
50 
ITT-E 
HIV4 
Listing of HIV-1 
Associated 
Conditions 
Data in both 
Phases will be 
included 
EOS 
51 
Safety 
AE8 
Listing of Non-
Serious AEs of 
Subjects at 
Mexico sites 
Mexican Safety 
Report 
requirement 
 
For EoS events 
in both phases 
will be included. 
EOS 


 
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Non-ICH Listings 
No. 
Population 
IDSL / TST ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
52 
Safety 
AE8 
Listing of SAEs 
of Subjects at 
Mexico sites 
Mexican Safety 
Report 
requirement 
 
 
For EoS events 
in both phases 
will be included. 
EOS 
53 
Safety 
AE8 
Listing of SAEs 
of Subjects at 
non-Mexico sites 
Mexican Safety 
Report 
requirement 
 
 
For EoS events 
in both phases 
will be included. 
 
Include the 
country in one 
column 
EOS 
65 
Safety-
Continuation 
Phase 
LIVER5 
Listing of Liver 
Event Results 
and Time of 
Event Relative to 
Treatment- 
Continuation 
Phase 
 
EOS 
69 
Safety 
MH2 
Listing of Past 
and Current Liver 
Disease Medical 
Conditions 
 
EOS 
70 
Safety-
Continuation 
Phase 
LB5 
Listing of 
Laboratory Data 
from Liver Event 
Follow-Up- 
Continuation 
Phase 
 
EOS  
71 
Safety-
Continuation 
Phase 
PREG1a 
Listing of 
Subjects Who 
Became 
Pregnant During 
the Study- 
Continuation 
Phase 
 
EOS 


 
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Non-ICH Listings 
No. 
Population 
IDSL / TST ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
82 
Safety-
Continuation 
Phase 
ECSSRS4 
Listing of C-
SSRS Suicidal 
Ideation and 
Behaviour Data- 
Continuation 
Phase 
 
Add another 
column to show 
positive or 
negative. 
 
 
EOS 
83 
Safety-
Continuation 
Phase 
PAN12 
Listing of 
COVID-19 
Assessments 
and Symptom 
Assessments- 
Continuation 
Phase 
New Output 
EOS 
86 
Safety-
Continuation 
Phase 
Same as Listing 13 
Listing of Start 
and Stop dates 
in the 
Continuation 
Phase 
New Output 
EOS 
76 
ITT=E 
Same shell as ARIA Week 
48 Listing 76 
Listing of All 
Genotypic Data 
Both 
Randomized 
and 
Continuation 
Phase will be 
included in 
separate pages 
EOS 
78 
ITT-E 
Same shell as ARIA Week 
48 Listing 78 
Listing of All 
Phenotypic Data 
Both 
Randomized 
and 
Continuation 
Phase will be 
included in 
separate pages 
EOS 
84 
Genotypic 
and/or 
Phenotypic  
/arenv/arprod/GSK1349572/ 
ING111762/ final_01/Listing 
37 
Listing of 
Genotypic and 
Phenotypic Data 
for Subjects 
Meeting 
Confirmed 
Virologic 
Withdrawal 
Criteria  
New Output; 
Both 
Randomized 
and 
Continuation 
Phase will be 
included in 
separate pages 
EOS 


 
CONFIDENTIAL 
 
 
 
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Non-ICH Listings 
No. 
Population 
IDSL / TST ID / Example 
Shell 
Title  
Programming 
Notes 
Deliverable  
85 
ITT-E 
/arenv/arprod/GSK1349572/ 
ING111762/ final_01/Listing 
38. 
Listing of 
Genotypic and 
Phenotypic Data 
for Subjects with 
On-Treatment 
Virology Results 
at Non-CVW 
Timepoints  
New Output; 
Both 
Randomized 
and 
Continuation 
Phase will be 
included in 
separate pages 
EOS 
 
12.14. Appendix 14: List of Data Displays 
12.14.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.n 
1.1 to 1.n 
Efficacy 
2.1 to 2.n 
2.1 to 2.n 
Safety 
3.1 to 3.n 
3.1 to 3.n 
Pharmacokinetic 
4.1 to 4.n 
4.1 to 4.n 
Pharmacodynamic and / or Biomarker 
5.1 to 5.n 
5.1 to 5.n 
Pharmacokinetic / Pharmacodynamic 
6.1 to 6.n 
6.1 to 6.n 
Virology 
7.1 to 7.n 
NA 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
12.14.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Appendix 15: Example Mock Shells for Data Displays. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Pharmacodynamic and / or Biomarker 
PD_Fn 
PD_Tn 
PD_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
 
 


 
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NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / TST ID / Example Shell’ or ‘Programming Notes’ column as 
‘[Non-Standard] + Reference.’ 
 
12.14.3. 
Deliverable 
Delivery  
Description 
WK48 
Week 48 Statistical Analysis Complete 
EOS 
Final End of Study Statistical Analysis Complete 
 


 
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12.14.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.1.  
All Subjects 
Screened  
SA1 
Summary of Study Populations 
CS CORE; 
 
WK48 
1.2.  
All Subjects 
Screened 
ES6 
Summary of Reasons for Screen Failure 
CS CORE 
WK48 
1.3.  
ITT(E) 
EudraCT age 
Summary of Age Categories 
CS CORE 
WK48 
1.4.  
ITT(E) 
ES1 
Summary of Subject Accountability: Randomized Phase 
Conclusion Record 
FDAAA, EudraCT 
WK48 
1.5.  
ITT(E) 
ES1 
Summary of Subject Accountability: Continuation Phase 
Conclusion Record 
FDAAA, EudraCT 
WK48 
1.6.  
ITT(E) 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by Visit 
 
WK48 
1.7.  
ITT(E) -
Continuation 
Phase 
DV1a 
Summary of Important Protocol Deviations 
CS CORE 
WK48, EOS 
1.8.  
ITT(E) 
SA2 
Summary of Protocol Deviations Leading to Exclusion from 
the Per-Protocol Population 
CS CORE 
WK48 
Demography 
1.9.  
ITT(E) 
DM1 
Summary of Demographic Characteristics 
CS CORE 
WK48 
1.10. 
ITT(E) 
DM5 
Summary of Race and Racial Combinations 
CS CORE 
WK48 
1.11. 
ITT(E) 
DM6 
Summary of Race and Racial Combinations Details 
CS CORE 
WK48 
1.12. 
ITT(E) 
 
Summary of Hepatitis Status at Entry 
 
WK48 
1.13. 
ITT(E) 
CDC1 
Summary of CDC Classification of HIV Infection at 
Baseline 
 
WK48 


 
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Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
1.14. 
ITT(E) 
RF1 
Summary of HIV Risk Factors 
 
WK48 
1.15. 
ITT(E) 
 
Summary of Baseline Cardiovascular Risk Assessments 
 
WK48 
1.16. 
ITT(E) 
 
Distribution of Quantitative Plasma HIV-1 RNA Results at 
Screening and Baseline 
 
WK48 
1.17. 
ITT(E) 
 
Distribution of CD4+ Cell Count (cells/mm^3) Results at 
Screening and Baseline 
 
WK48 
Medical Conditions, Concomitant Medications & ART 
1.18. 
ITT(E) 
MH1 
Summary of Current Medical Conditions 
CS CORE 
WK48 
1.19. 
ITT(E) 
MH1 
Summary of Past Medical Conditions 
CS CORE 
WK48 
1.20. 
ITT(E) 
MH4 
Summary of Current Cardiac, Gastrointestinal, Metabolism 
and Nutrition, Psychiatric, Renal and Urinary, and Nervous 
System Conditions 
 
WK48 
1.21. 
ITT(E) 
MH4 
Summary of Past Cardiac, Gastrointestinal, Metabolism 
and Nutrition, Psychiatric, Renal and Urinary, and Nervous 
System Conditions 
 
WK48 
1.22. 
ITT(E) 
CM1 
Summary of Concomitant Medication by Ingredient ATC 
Level 1 
 
WK48 
1.23. 
ITT(E) 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations 
 
WK48 
1.24. 
ITT(E) 
CM1b 
Summary of Concomitant Medication by Combination Term 
ATC Level 1 
 
WK48 
1.25. 
ITT(E) 
 
Summary of Lipid Modifying Agent Use at Baseline 
 
WK48 
1.26. 
ITT(E) 
 
Summary of Lipid Modifying Agent Use Starting Post-
Baseline 
 
WK48 


 
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Study Population Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
1.27. 
All Subjects 
Screened 
 
Summary of Subjects by Country and Investigator 
 
WK48 
 


 
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12.14.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Primary Efficacy Analyses 
2.1.  
ITT(E) 
 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 – Snapshot 
Analysis 
 
WK48 
2.2.  
Per-
Protocol  
 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 – Snapshot 
Analysis 
 
WK48 
2.3.  
ITT 
 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 – Snapshot  
Analysis 
 
WK48 
2.4.  
ITT(E) 
 
Summary of Study Outcomes (<50 c/mL) at Week 48 – 
Snapshot Analysis 
 
WK48 
2.5.  
ITT(E) 
 
Treatment by Strata Tests of Homogeneity for Proportion 
of Subjects with Plasma HIV-1 RNA <50 c/mL at Week 48 - 
Snapshot Analysis 
 
WK48 
Secondary Efficacy Analyses 
2.6.  
ITT(E) 
 
Summary of Proportion of Subjects with Plasma HIV-1 RNA 
<50 c/mL at Week 48 by Subgroup - Snapshot Analysis 
 
WK48 
2.7.  
ITT(E) 
 
Summary of Change from Baseline in Plasma HIV-1 RNA 
(log10 c/mL) by Visit 
 
WK48, EOS 
2.8.  
ITT(E) 
 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Visit – Snapshot Analysis 
 
WK48 
2.9.  
ITT(E) 
 
Proportion of Subjects with Plasma HIV-1 RNA <400 c/mL 
by Visit – Snapshot Analysis 
 
WK48 


 
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Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.10. 
ITT(E) 
 
Summary of Study Outcomes (<400 c/mL) at Week 48 – 
Snapshot Analysis 
 
WK48 
2.11. 
ITT(E) 
 
Summary of Kaplan-Meier Estimates of Proportion of 
Subjects Without Confirmed Virologic Withdrawal at Week 
48  
- Treatment Related Discontinuation = Failure  
 
WK48 
2.12. 
ITT(E) 
 
Summary of Kaplan-Meier Estimates of Proportion of 
Subjects Without Confirmed Virologic Withdrawal at Week 
48  
- Efficacy Related Discontinuation = Failure 
 
WK48 
2.13. 
ITT(E) 
Same shell as 
ARIA Week 48 
Proportion of Subjects Meeting Confirmed Virologic 
Withdrawal Criteria by Visit- Observed Case 
 
WK48, EOS 
2.14. 
ITT(E) 
 
Distribution of Quantitative Plasma HIV-1 RNA Results at 
Suspected and Confirmation of Confirmed Virologic 
Withdrawal 
 
WK48 
2.15. 
ITT(E) 
Same shell as 
ARIA Week 48 
Summary of Change from Baseline in CD4+ Cell Count 
(cells/mm^3) by Visit 
 
WK48, EOS 
2.16. 
ITT(E) 
HIV1 
Summary of Post-Baseline HIV-1 Associated Conditions 
Including Recurrences 
 
WK48, EOS 
2.17. 
ITT(E) 
HIV1 
Summary of Post-Baseline HIV-1 Associated Conditions 
Excluding Recurrences 
 
WK48, EOS 
2.18. 
ITT(E) 
HIV2 
Summary of Post-Baseline HIV-1 Disease Progressions 
 
WK48, EOS 
2.19. 
ITT(E) 
gsk2619619/
mid200336/ 
final_01/table 
2.1 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Visit – Observed Case 
 
EOS 


 
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12.14.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Insert Endpoint Category 
2.1.  
ITT(E) 
 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 c/mL 
by Visit – Snapshot Analysis 
Line plot 
WK48 
2.2.  
ITT(E) 
Same shell as 
Gemini Figure 
2.3 
Individual Plasma HIV-1 RNA (log10 c/mL) and CD4+ 
Profiles by Visit for Subjects with at least One Suspected 
Virologic Withdrawal Visit 
 
WK48, EOS 
2.3.  
ITT(E) 
 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA <50 c/mL at Week 48 by 
Subgroup – Snapshot Analysis 
 
WK48 
 


 
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12.14.7. 
Safety Figures 
Safety : Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Insert Endpoint Category 
3.1.  
Safety 
AE10 
Plot of Common Adverse Events and Relative Risk 
CS CORE 
WK48 
3.2.  
Safety 
LIVER9 
Scatter Plot of Maximum vs. Baseline for ALT 
CS CORE 
 
WK48 
3.3.  
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin 
CS CORE 
 
WK48, EOS 
3.4.  
Safety 
 
Line Plot of mean change from Baseline in Creatinine  
 
WK48 
3.5.  
Safety 
 
Bar Chart of Triglycerides (mmol/L) NCEP Categories at 
Week 48 vs. Baseline 
 
WK48 
3.6.  
Safety 
 
Bar Chart of Total Cholesterol (mmol/L) NCEP Categories 
at Week 48 vs. Baseline 
 
WK48 
3.7.  
Safety 
 
Bar Chart of HDL Cholesterol (mmol/L) NCEP Categories 
at Week 48 vs. Baseline 
 
WK48 
3.8.  
Safety 
 
Bar Chart of LDL Cholesterol (mmol/L) NCEP Categories 
at Week 48 vs. Baseline 
 
WK48 
3.9.  
Safety 
 
Bar Chart of Total Cholesterol/ HDL Ratio at Week 48 vs. 
Baseline 
 
WK48 


 
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12.14.8. 
Health Outcomes Tables 
Health Outcomes : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
SF-12 
6.1.  
ITTE 
 
Summary of SF-12 Individual Item Scores - LOCF 
 
WK48 
6.2.  
ITTE 
 
Summary of SF-12 Total score, MCS and PCS by Visit - LOCF 
Results to go into summary stats come 
from a computer analysis progam 
WK48 
6.3.  
ITTE 
 
Summary of SF-12 Total score, MCS and PCS by Visit - 
Observed 
Results to go into summary stats come 
from a computer analysis progam 
WK48 
6.4.  
ITTE 
 
Summary of Change from Baseline at Week 48 in SF-12 Total 
score, MCS and PCS - LOCF 
Results to go into summary stats come 
from a computer analysis progam 
WK48 
6.5.  
ITTE 
 
Summary of Change from Baseline at Week 48 in SF-12 Total 
score, MCS and PCS - Observed 
Results to go into summary stats come 
from a computer analysis progam 
WK48 
HIVTSQs 
6.6.  
ITTE 
 
Summary of HIVTSQs Individual Item Scores by Visit - LOCF 
 
WK48 
6.7.  
ITTE 
 
Summary of HIVTSQs Total Score by Visit - LOCF 
 
WK48 
6.8.  
ITTE 
 
Summary of HIVTSQs Total Score by Visit - Observed 
 
WK48 
6.9.  
ITTE 
 
Summary of HIVTSQs Lifestyle/ease Sub-score by visit - LOCF  
 
WK48 
6.10. 
ITTE 
 
Summary of HIVTSQs Lifestyle/ease Sub-score by visit - 
Observed  
 
WK48 
6.11. 
ITTE 
 
Summary of HIVTSQs General Satisfaction/Clinical Sub-score 
by visit - LOCF 
 
WK48 
6.12. 
ITTE 
 
Summary of HIVTSQs General Satisfaction/Clinical Sub-score 
by visit - Observed 
 
WK48 
 


 
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12.14.9. 
Virology Tables 
Virology : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Genotype 
7.1. 
Genotypic 
 
Summary of INI Mutations at time of CVW 
 
WK48 
7.2. 
Genotypic 
 
Summary of Treatment Emergent INI Mutations at time of 
CVW 
 
WK48 
7.3. 
Genotypic 
 
Summary of Major Mutations of NRTI, NNRTI and PI 
Classes at time of CVW  
 
WK48 
7.4. 
Genotypic 
 
Summary of Treatment Emergent Major Mutations of NRTI, 
NNRTI and PI Classes at time of CVW 
 
WK48 
Phenotype 
7.5. 
Phenotypic 
 
Summary of Phenotype at time of CVW by phenotypic cut-
off 
For EoS both phases will be 
included 
WK48, EOS 
7.6. 
Phenotypic 
 
Summary of Phenotype at time of CVW by Number of 
Drugs to Which Subject are Resistant 
 
WK48 
7.7. 
Phenotypic 
 
Summary of Fold Change at Baseline and Time of CVW 
For EoS both phases will be 
included. 
WK48, EOS 
7.8. 
Phenotypic 
 
Summary of Change from Baseline in Fold Change at Time 
of CVW 
 
WK48 
 


 
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12.14.10. Safety Tables 
Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Exposure 
3.1.  
Safety 
 
Summary of Extent of Exposure to Investigational Product 
– Randomised Phase 
CS Core 
WK48 
3.2.  
Safety 
 
Summary of Extent of Exposure to Investigational Product 
– Randomisation and Continuation Phase 
CS Core 
 
WK48, EOS 
Adverse Events 
3.3.
Safety 
AE5 
Summary of All Adverse Events by System Organ Class 
and Maximum Toxicity-Randomised Phase 
CS Core 
 
WK48, EOS 
3.4.  
Safety 
AE3 
Summary of Common (>=3%) Adverse Events by Overall 
Frequency-Randomised Phase 
CS Core 
 
WK48, EOS 
3.5.  
Safety 
AE3 
Summary of Common (>=3%) Grade 2-4 Adverse Events 
by Overall Frequency-Randomised Phase 
CS Core 
 
WK48, EOS 
3.6.  
Safety 
AE5 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity-Randomised Phase  
CS Core 
 
WK48, EOS 
3.7.  
Safety 
AE3 
Summary of Common (>=3%) Drug-Related Grade 2-4 
Adverse Events by Overall Frequency-Randomised Phase 
CS Core 
 
WK48, EOS 
3.8.  
Safety 
AE1 
Summary of Serious Adverse Events by System Organ 
Class – Randomised Phase 
CS Core 
WK48 
3.9.  
Safety 
AE1 
Summary of Serious Adverse Events by System Organ 
Class – Randomised and Continuation Phase 
CS Core 
 
New output.  
FDAAA, EudraCT 
 
WK48, EOS 


 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.10. 
Safety 
AE1 
Summary of Drug-Related Serious Adverse Events by 
System Organ Class-Randomised Phase 
CS Core 
 
Plain Language Summary (PLS) 
requirements 
 
 
WK48 
3.11. 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product – Randomised Phase 
CS Core 
WK48 
3.12. 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product – Randomised and Continuation Phase 
CS Core 
 
WK48, EOS 
3.13. 
Safety 
AE3 
Summary of Common (>=3%) Non-Serious Adverse 
Events-Randomised and Continuation Phase 
CS Core 
FDAAA 
 
 
 
WK48, EOS 
3.14. 
Safety 
EudraCT Non-
serious AE 
Summary of Subjects and Number of Occurrences of 
Common (>=3%) Non-Serious Adverse Events by System 
Organ Class-Randomised and Continuation Phase 
CS Core 
EudraCT  
 
 
 
WK48, EOS 
3.15. 
Safety 
EudraCT SAE 
Summary of Subjects and Number of occurrences of 
SAEs, Drug-related AEs, Fatal SAEs, and Drug-related 
SAEs-Randomised and Continuation Phase 
CS Core 
EudraCT  
 
 
 
WK48, EOS 


 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Laboratory 
3.16. 
Safety 
LB1 
Summary of Chemistry Changes from Baseline by Visit 
CS Core 
 
WK48 
3.17. 
Safety 
LB1 
Summary of Lipids Percentage Changes from Baseline by 
Visit 
 
WK48 
3.18. 
Safety 
LB1 
Summary of Hematology Changes From Baseline by Visit 
CS Core 
 
WK48 
3.19. 
Safety 
LB1 
Summary of Urine Concentrations Changes from Baseline 
by Visit 
CS Core 
 
WK48 
3.20. 
Safety 
 
Summary of Maximum Post-Baseline in Urinalysis Dipstick 
Results   
 
WK48 
3.21. 
Safety 
 
Summary of Changes in Proteinuria Baseline Laboratory 
Result to Maximum Post-Baseline Laboratory Result -
Randomised Phase 
i.e., “shift table” 
WK48 
3.22. 
Safety 
 
Summary of Changes in NCEP Lipid Baseline Category to 
Maximum Post-Baseline Category - Triglycerides 
Randomised Phase 
 
WK48 
3.23. 
Safety 
 
Summary of Changes in NCEP Lipid Baseline Category to 
Maximum Post-Baseline Category – Total Cholesterol 
Randomised Phase 
 
WK48 
3.24. 
Safety 
 
Summary of Changes in NCEP Lipid Baseline Category to 
Maximum Post-Baseline Category – HDL Cholesterol 
Randomised Phase 
 
WK48 
3.25. 
Safety 
 
Summary of Changes in NCEP Lipid Baseline Category to 
Maximum Post-Baseline Category – LDL Cholesterol 
Randomised Phase 
 
WK48 


 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.26. 
Safety 
 
Summary of TC/HDL ratio Changes from Baseline 
Randomised Phase 
 
WK48 
3.27. 
Safety 
 
Summary of Bone Markers Changes from Baseline 
Randomised Phase 
 
WK48 
3.28. 
Safety 
 
Summary of Maximum Post-Baseline Emergent Chemistry 
Toxicities – Randomised Phase 
CS Core 
WK48 
3.29. 
Safety 
 
Summary of Maximum Post-Baseline Emergent Chemistry 
Toxicities – Randomised and Continuation Phase 
CS Core 
 
WK48, EOS 
3.30. 
Safety 
 
Summary of Maximum Post-Baseline Emergent 
Hematology Toxicities – Randomised Phase 
CS Core 
WK48 
3.31. 
Safety 
 
Summary of Maximum Post-Baseline Emergent 
Hematology Toxicities – Randomised and Continuation 
Phase 
CS Core 
 
WK48, EOS 
3.32. 
Safety 
 
Statistical analysis of Change from Baseline in 
Triglycerides at Week 48 (Multiple imputed Dataset - MAR) 
 
WK48 
3.33. 
Safety 
 
 Statistical analysis of Change from Baseline in 
Triglycerides at Week 48 - OC Dataset 
 
WK48 
3.34. 
Safety 
 
Statistical analysis of Change from Baseline in 
Triglycerides at Week 48 - Lipid LOCF Dataset 
 
WK48 
3.35. 
Safety 
 
Statistical analysis of Change from Baseline in 
Triglycerides at Week 48 - Repeated Measures Mixed 
Model Analysis 
 
WK48 
3.36. 
Safety 
 
Statistical analysis of Change from Baseline in TC/HDL 
Ratio at Week 48 (Multiple imputed Dataset - MAR) 
 
WK48 
3.37. 
Safety 
 
Statistical analysis of Change from Baseline in TC/HDL 
Ratio at Week 48 - Observed Case 
 
WK48 


 
CONFIDENTIAL 
 
 
 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.38. 
Safety 
 
Statistical analysis of Change from Baseline in TC/HDL 
Ratio at Week 48 - Lipid LOCF 
 
WK48 
3.39. 
Safety 
 
Statistical analysis of Change from Baseline in TC/HDL 
Ratio at Week 48 - Repeated Measures Mixed Model 
Analysis 
 
WK48 


 
CONFIDENTIAL 
 
 
 
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Safety : Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Other 
3.40. 
Safety 
ABC_HSR1 
Summary of the Incidence of Abacavir Hypersensitivity 
Reaction Classified as SAEs 
Safety population, subset to 
those exposed to abacavir.  Total 
column combines all treatment 
groups. 
WK48 
3.41. 
Safety 
OLIVER1 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria at Any Post-Baseline Visit 
 
WK48, EOS 
3.42. 
Safety 
 
Subjects Meeting Hepatobiliary Abnormality Criteria - Post-
Baseline Emergent 
 
WK48, EOS 
3.43. 
Safety 
 
Summary of Positive Suicidal indication Alerts based on 
eCSSRS by Visit 
 
WK48 
3.44. 
Safety 
 
Statistical Analysis of Bone Specific Alkaline Phosphatase 
(Ratio of Week 48 Result over Baseline)  
 
WK48 
3.45. 
Safety 
 
Statistical Analysis of Type I Collagen C-Telopeptides 
(Ratio of Week 48 Result over Baseline)  
 
WK48 
3.46. 
Safety 
 
Statistical Analysis of Osteocalcin (Ratio of Week 48 
Result over Baseline)  
 
WK48 
3.47. 
Safety 
 
Statistical Analysis of Procollagen 1 N-Terminal Propeptide 
(Ratio of Week 48 Result over Baseline)  
 
WK48 
3.48. 
Safety 
 
Statistical Analysis of Vitamin D (Ratio of Week 48 Result 
over Baseline)  
 
WK48 
3.49. 
Safety 
 
Summary of All Adverse Events by System Organ Class - 
Randomised Phase  
 
WK48 
 


 
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12.14.11. ICH Listings 
ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Study Population 
1.  
Randomized 
TA1 
Listing of Randomized and Actual Strata and Treatment 
Assignment 
CS CORE 
 
 
WK48 
2.  
All Subjects 
Screened 
ES7 
Listing of Reasons for Screen Failure 
CS CORE 
WK48 
3.  
Randomized 
 
Listing of Subjects Randomized But Not Treated 
CS CORE  
(related to ‘Listing for exclusion 
from any population) 
WK48 
4.  
ITT-E 
ES2 
Listing of Reasons for Study Withdrawal 
CS CORE 
 
WK48, EOS 
5.  
ITT-E 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
CS CORE 
WK48 
6.  
ITT-E 
 
Listing of Important Protocol Deviations  
CS CORE 
 
WK48, EOS 
7.  
ITT-E 
 
Listing of Protocol Deviations Leading to Exclusion from 
the Per-Protocol Population 
CS CORE  
(add listing for exclusion of other 
populations?) 
WK48 
8.  
ITT-E 
DM2 
Listing of Demographic Characteristics 
CS CORE 
WK48 
9.  
ITT-E 
DM9 
Listing of Race 
CS CORE 
WK48 
Efficacy 
10.  
ITT-E 
 
Listing of Quantitative Plasma HIV-1 RNA Data 
 
WK48, EOS 
11.  
ITT-E 
 
Listing of Study Outcome (<50 c/mL) at Week 48 – 
Snapshot Analysis 
 
WK48 


 
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ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
12.  
ITT-E 
 
Listing of Study Outcome (<400 c/mL) at Week 48 – 
Snapshot Analysis 
 
WK48 
Safety 
13.  
Safety 
HIV_IP5 
Listing of Investigational Product Exposure Data 
CS CORE 
 
 
WK48, EOS 
14.  
Safety 
 
Listing of Investigational Product Exposure Data - Mexican 
Subjects  
 
WK48 
15.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events  
CS CORE 
 
WK48 
16.  
Safety 
AE8 
Listing of All Adverse Events 
CS CORE 
 
WK48, EOS 
17.  
Safety 
AE8 
Listing of Fatal Adverse Events 
CS CORE 
 
WK48, EOS 
18.  
Safety 
AE8 
Listing of Non-Fatal Serious Adverse Events 
CS CORE 
 
WK48, EOS 
19.  
Safety 
AE8 
Listing of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product 
CS CORE 
 
WK48, EOS 
20.  
Safety-
Continuation 
Phase 
AE2 
Listing of Relationship of Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text 
CS CORE 
For EoS only report events in the 
Continuation Phase; 
Add “-Continuation Phase to the 
title” 
 
WK48, EOS 


 
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ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
21.  
Safety 
SAE Reasons 
Listing of Reasons for Considering as a Serious Adverse 
Event 
CS CORE 
FDA 
 
WK48 
22.  
Safety 
LB5 
Listing of Clinical Chemistry Laboratory Data for Subjects 
with Laboratory Abnormalities of Potential Clinical Concern 
CS CORE 
 
WK48, EOS 
23.  
Safety 
LB5 
Listing of Hematology Laboratory Data for Subjects with  
Laboratory Abnormalities of Potential Clinical Concern 
CS CORE 
 
WK48 
24.  
Safety 
UR2a 
Listing of Urinalysis Data for Subjects with Abnormalities of 
Potential Clinical Concern 
CS CORE 
 
WK48 
25.  
Safety 
PSRAE1 
Listing of Possible Suicidality-Related Adverse Event Data: 
Event and Description (Section 1- Section 2) 
 
WK48, EOS 
26.  
Safety 
PSRAE3 
Listing of Possible Suicidality-Related Adverse Event Data: 
Possible Cause(s) (Section 3) 
 
WK48, EOS 
27.  
Safety 
PSRAE4 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 4) 
 
WK48, EOS 
28.  
Safety 
PSRAE5 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 5- Section 8) 
 
WK48, EOS 
12.14.12. Non-ICH Listings 
Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Study Population 
29.  
All Subjects 
Screened 
 
Listing of Study Populations 
 
WK48, EOS 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
30.  
All Subjects 
Screened 
 
Listing of Subject Recruitment by Country and Site Number  
WK48 
31.  
All Subjects 
Screened 
 
Listing of Rescreened Subjects 
 
WK48 
32.  
ITT-E 
 
Listing of Visit Dates 
 
WK48, EOS 
33.  
ITT-E 
 
Listing of Hepatitis Test Results 
 
WK48 
34.  
ITT-E 
CDC3 
Listing of CDC Classification of HIV Infection at Baseline 
 
WK48 
35.  
ITT-E 
RF2 
Listing of HIV Risk Factors 
 
WK48 
36.  
ITT-E 
MH2 
Listing of Current and Past Medical Conditions at Baseline 
 
WK48 
37.  
ITT-E 
 
Listing of Current and Past Medical Conditions at Baseline 
- Mexican subjects only  
 
WK48 
38.  
ITT-E 
 
Listing of Baseline Cardiovascular Risk Assessment Data 
 
WK48 
39.  
ITT-E 
 
Listing of History of Cardiac Therapeutic Procedures 
 
WK48 
40.  
ITT-E 
 
Listing of Investigational Product Accountability 
 
WK48, EOS 
41.  
ITT-E 
CM2 
Listing of Concomitant Medications 
CS CORE 
 
WK48, EOS 
42.  
ITT-E 
 
Listing of Concomitant Medications - Mexican subjects only   
WK48 
43.  
ITT-E 
CM6 
Listing of Relationship Between ATC Level 1, Ingredient 
and Verbatim Text 
 
WK48 
44.  
ITT-E 
CM2 
Listing of Prior ART Medications 
 
WK48 
45.  
ITT-E 
CM2 
Listing of Concomitant ART Medications 
 
WK48, EOS 
46.  
ITT-E 
 
Listing of Concomitant ART Medications - Mexican 
subjects only  
 
WK48 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
47.  
ITT-E 
CM6 
Listing of Relationship Between ATC Level 4, Ingredient 
and Verbatim Text 
 
WK48 
Efficacy 
48.  
ITT-E 
Same shell as 
ARIA Week 48 
Listing of Subjects with Confirmed Virologic Withdrawal 
 
WK48, EOS 
49.  
ITT-E 
Same shell as 
ARIA Week 48 
Listing of CD4+ Cell Count Data 
 
WK48, EOS 
50.  
ITT-E 
HIV4 
Listing of HIV-1 Associated Conditions 
 
WK48, EOS 
Safety 
51.  
Safety 
AE8 
Listing of Non-Serious AEs of Subjects at Mexico sites 
Mexican Safety Report 
requirement 
 
For EoS events in both phases 
will be included. 
WK48, EOS 
52.  
Safety 
AE8 
Listing of SAEs of Subjects at Mexico sites 
Mexican Safety Report 
requirement 
 
 
 
WK48, EOS 
53.  
Safety 
AE8 
Listing of SAEs of Subjects at non-Mexico sites 
Mexican Safety Report 
requirement 
 
 
 
 
WK48, EOS 
54.  
Safety 
AE8 
Listing of Pre-treatment Adverse Events 
 
WK48 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
55.  
Safety 
 
Listing of Cardiovascular Events  
 
WK48 
56.  
Safety 
VS4 
Listing of Vital Signs 
 
WK48 
57.  
Safety 
ABC_HSR 
_EXPO2 
Listing of Abacavir Hypersensitivity Reaction Record -  
Exposure to Abacavir 
 
WK48 
58.  
Safety 
ABC_HSR 
_DRUG2 
Listing of Abacavir Hypersensitivity Reaction Record -  
Subject History of Drug Allergies 
 
WK48 
59.  
Safety 
ABC_HSR 
COND2 
Listing of Abacavir Hypersensitivity Reaction Record -  
Subject and Family Conditions 
 
WK48 
60.  
Safety 
ABC_HSR 
_RASH2 
Listing of Abacavir Hypersensitivity Reaction Record -  
Skin Rash Details 
 
WK48 
61.  
Safety 
ABC_HSR 
_SYMP4 
Listing of Abacavir Hypersensitivity Reaction Record -  
Symptoms 
 
WK48 
62.  
Safety 
VS4 
Listing of Abacavir Hypersensitivity Reaction Record -  
Vital Signs 
 
WK48 
63.  
Safety 
ABC_HSR 
_SYMP6 
Listing of Abacavir Hypersensitivity Reaction Record - 
Individual Symptoms and Diagnostic Category 
Assignments (Excluding Other Symptoms) 
 
WK48 
64.  
Safety 
ABC_HSR 
_SYMP7 
Listing of Abacavir Hypersensitivity Reaction Record - 
Individual Symptoms and Diagnostic Category 
Assignments (Other Symptoms) 
 
WK48 
65.  
Safety 
LIVER5 
Listing of Liver Event Results and Time of Event Relative 
to Treatment 
 
WK48, EOS 
66.  
Safety 
LIVER6 
Listing of Liver Event Information for RUCAM Score 
 
WK48 
67.  
Safety 
LIVER7 
Listing of Liver Biopsy Details 
 
WK48 
68.  
Safety 
LIVER8 
Listing of Liver Imaging Details 
 
WK48 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
69.  
Safety 
MH2 
Listing of Past and Current Liver Disease Medical 
Conditions 
 
WK48, EOS 
70.  
Safety 
LB5 
Listing of Laboratory Data from Liver Event Follow-Up 
 
WK48, EOS  
71.  
Safety 
PREG1a 
Listing of Subjects Who Became Pregnant During the 
Study 
 
WK48, EOS 
72.  
Safety 
ECSSRS4 
Columbia Suicidality  
 
 
WK48, EOS 
  81. 
Safety 
 
Listing of Post Baseline Maximum ALT and Maximum 
Bilirubin - Randomised Phase  
 
WK48 
  82. 
Safety 
 
Listing of Positive Suicidal Alerts Based on eCSSRS 
 
WK48 
Health Outcomes 
 
75. 
ITT-E 
 
Listing of HIVTSQs 
 
WK48 
Pharmacokinetic Analysis 
  80. 
Safety 
 
Listing of Pharmacokinetic Concentration Data 
 
WK48 
Virology 
76. 
Genotypic 
ARIA Week 48 
Listing 76 
Listing of All Genotypic Data 
Both Randomized and 
Continuation Phase will be 
included in separate pages 
WK48, EOS 
77. 
Genotypic 
 
Listing of Treatment Emergent Genotypic Mutations 
 
WK48 
78. Phenotypic 
ARIA Week 48 
Listing 78 
Listing of All Phenotypic Data 
Both Randomized and 
Continuation Phase will be 
included in separate pages 
WK48, EOS 


 
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Non-ICH : Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title  
Programming Notes 
Deliverable  
79. Phenotypic 
 
Listing of Replication Capacity 
 
WK48 
 
12.15. Appendix 15: Example Mock Shells for Data Displays 
Data display specifications will be uploaded as separate document.