A Dose-ranging Study to Compare the Safety and Immunogenicity of a Candidate Human Deficiency Virus (HIV) Vaccine 732461, Adjuvanted or Not, Administered According to a 0, 1 Month Schedule to Healthy Adult HIV Seronegative Volunteers.
Phase: PHASE2
Conditions: AIDS, HIV Infections
Sponsor: GlaxoSmithKline

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CONFIDENTIAL 
Amendment 2 
Jacques Bruhwyler 
Clara van der Zee, 
Pierre Vandepapeliere, 
PPD 
Lisa Mc Nally 
Marie-Ange Demoitie, 
Gerald Voss, 
Marguerite Koutsoukos, 
Olga Rovira, 
Els De Kock, 
Evi De Ruymaeker, 
Isabelle Carletti, 
 
 
CONFIDENTIAL  
 
 
Sponsor: 
 
108706 (PRO HIV-005) 
Amendment 2 
GlaxoSmithKline Biologicals 
89, rue de l'Institut 
1330 Rixensart 
Belgium 
Study vaccine 
GSK Biologicals candidate HIV prophylactic vaccine 
F4co (p24-RT-Nef-p17) adjuvanted with AS01B 
Study vaccine number 
732461 
eTrack study number and 
abbreviated title 
108706 (PRO HIV-005) 
EudraCT number 
2006-003796-12 
Date of approval 
December 5, 2006 (final) 
Date of amendment 1 
September 24, 2007 
Date of amendment 2 
October 08, 2007 
Title 
Dose-ranging study to evaluate the safety and 
immunogenicity of GSK Biologicals' HIV vaccine 
732461, adjuvanted or not, when administered as a 3 
2-dose schedule to healthy adult HIV seronegative 
volunteers, aged 18 to 40 years. (Amended 
September 24, 2007) 
Detailed title 
A Phase I-II partially-blinded, randomized, dose- 
ranging study (10-30-90 g) to compare the safety and 
immunogenicity of GSK Biologicals' candidate HIV 
vaccine F4co (p24-RT-Nef-p17), adjuvanted or not 
with AS01B, administered intramuscularly according 
to a vaccination schedule of 0, 1, 6 months to healthy 
adult HIV seronegative volunteers, aged 18 to 40 
years. (Amended September 24, 2007) 
Co-ordinating author 
 PPD 
PPD 
Operations 
, PhD, Squarepoint-Pointcarre 
PhD, Scientific writer, Clinical 
Contributing authors 
 
MD, Director, Exploratory 
Clinical R&D 
PPD 
Manager 
, MD, Lead Clinical Development 
 
Sc, Scientist, R&D 
ctor, R&D 
MSc, Project Manager, R&D 
ciate Scientist, Technical 
Regulatory Affairs 
PPD 
PPD 
PPD 
MSc, Central Study Coordinator 
Central Study Coordinator 
PhD, Biostatistician 
GSK Biologicals' Protocol OS V 12.2 
Copyright 2006 the GlaxoSmithKline group of companies. All rights reserved. Unauthorized copying or 
use of this information is prohibited. 
PPD 
M
PPD 
PhD, Dire 
PPD 
PPD 
MSc, Asso

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Geert Leroux-Roels 
De 
Pintelaan, 185, 9000 Ghent, 
PPD 
Lisa Mc Nally, 
+32.2.656.33.05 
+32.2.656.80.44 
Els De Kock Evi De Ruymaeker 
+32.2.656.79.24 37.60 
+32.2.656. 80.44 
Els De Kock, 
+32.2.656.79.24 
+32.2.656. 80.44 
+32.2.656.SS.50 
+32.2.656.S0.09 or +32.2.656.51.16 
+32.477.404.713 
+32.474.534.S6S 
 
 or 
 
Sponsor Information 
eTrack study number 
108706 
 
eTrack abbreviated title 
108706 (PRO HIV-005) 
EudraCT number 
2006-003796-12 
 
1. Principal Investigator 
 
Prof. Dr. PPD 
 , Center for Vaccinology, Ghent University Hospital, 
Belgium. 
 
2. Medical Monitor 
 
Dr. PPD 
Lead Clinical Development Manager 
GlaxoSmithKline Biologicals 
Phone: PPD 
Fax: 
3. Study Monitor 
 
PPD 
GlaxoSmithKline Biologicals 
Phone: PPD 
Fax: 
, Central Study Coordinator 
 
(Amended September 24, 2007 
 
 
4. Study Contact for Reporting of a Serious Adverse Event 
 
PPD 
Central Study Coordinator 
GlaxoSmithKline Biologicals 
Phone: 
 
 
 
GSK Biologicals Clinical Safety Physician 
GlaxoSmithKline Biologicals 
Phone: PPD 
Fax: PPD 
Mobile phone /or 717 day availability: 
 
Back-up mobile phone contact: 
PPD 
(Amended September 24, 2007) 
 
5. Study Contact for Emergency Code Break 
 
GSK Biologicals Clinical Safety Physician 
GlaxoSmithKline Biologicals 
Phone: 
Fax:  
Mobile phone for 717 day availability: 
PPD 
PPD 
PPD 
PPD 
PPD 
Fax: 
PPD 
PPD
PPD
PPD

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+32.474.534.868 
+32.477.404.713  
Back-up mobile phone contact: 
 
PPD 
PPD 

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Synopsis 
Title 
A Phase I-II partially-blinded, randomized, dose- ranging 
study (10-30-90 g) to compare the safety and 
immunogenicity of GSK Biologicals' candidate HIV vaccine 
F4co (p24-RT-Nef-p17), adjuvanted or not with AS01B, 
administered intramuscularly according to a vaccination 
schedule of 0, 1, 6 months to healthy adult HIV seronegative 
volunteers, aged 18 to 40 years. (Amended September 24, 
2007) 
 
Indication/Study 
population 
Healthy HIV seronegative adults, 18--40 years of age 
 
Rationale 
The most prominent immune effector mechanisms directed 
against HIV are neutralizing antibodies and CD8+ T cells. In 
addition, accumulating evidence suggests that CD4+ T cells, 
which provide essential help to the other compartments of an 
adaptive immune response, are equally crucial for the 
induction of effective HIV immunity. In particular, the 
analysis of immune responses in HIV-infected individuals 
suggests a crucial role for CD4+ T cells. It appears that CD4+ 
cells provide essential help to CD8+ effector cells in long- 
term non-progressors. In contrast, the absence of HIV-specific 
CD4+ T cells in chronically infected individuals seems to be 
related to an impairment of CD8+ T cell maturation into 
effector cells. Thus, it appears that in order to maintain 
functional CD8+ T cell immunity, strong and broad CD4+ T 
cell responses are required and that these responses should be 
induced by an effective HIV vaccine. 
 
Probably the most potent approach to induction of CD4+ T 
cell responses is the use of adjuvanted protein vaccines. 
Indeed, GSK's previous candidate HIV vaccines consisted of 
two recombinant proteins, gp120 and NefTat, which were 
formulated in potent proprietary adjuvants (AS01B, AS02A 
and AS02V). These vaccines were shown to induce very 
potent CD4+ T cell responses in two independent clinical 
trials (HVTN-041 and HIV-002). The gp120 antigen was the 
most immunogenic vaccine component, and the Nef and Tat- 
directed responses were lower in comparison. 
 
AS01B (liposome-based formulation containing the 
immunostimulants 3D-MPL [3-deacylated monophosphoryl 
lipid A] and QS21 [a triterpene glycoside purified from the 
bark of Quillaja saponaria]) was chosen among other potent 
proprietary adjuvants, from several clinical studies (for 
exhaustive details please refer to the Investigator's Brochure) 

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for its propensity to induce a stronger Th1 cellular-mediated 
immune response and its acceptable safety profile. 
 
Since such CD4+ cell responses need to cover the broadest 
possible spectrum of circulating HIV strains, an HIV vaccine 
should contain many different CD4 epitopes from different 
viral proteins. It was therefore desirable to include well- 
conserved and highly immunogenic HIV antigens in an 
improved vaccine formulation. The viral antigens that contain 
the highest number of conserved T cell epitopes are Gag, Pol, 
and Nef. Consequently, GSK chose to include these antigens 
as a single fusion protein (F4co) into an adjuvanted (AS01B) 
vaccine formulation. 
 
Objectives 
Primary 
 
• 
To evaluate the reactogenicity and safety of the candidate 
vaccine F4co (p24-RT-Nef-p17) with or without AS01B 
adjuvant at three different doses (10-30-90 g). 
• 
To evaluate the CD4+ T-cell response to the candidate 
vaccine F4co (p24-RT-Nef-p17) with or without AS01B 
at three different doses (10-30-90 g) in terms of 
proportion of responders to at least 1, 2, 3 antigens and to 
all 4 antigens determined two weeks after the second 
vaccination. 
Secondary 
 
• 
To evaluate the CD4+ T-cell immune response to the 
candidate vaccine F4co (p24-RT-Nef-p17) with or 
without AS01B at three different doses (10-30-90 g) 
after two and three vaccinations. 
• 
To evaluate the serological response to the candidate 
vaccine F4co (p24-RT-Nef-p17) with or without AS01B 
at three different doses (10-30-90 g) after two and three 
vaccinations. (Amended September 24, 2007) 
• 
To evaluate the persistence of cell-mediated and 
serological responses to the candidate vaccine F4co (p24- 
RT-Nef-p17) with or without AS01B at three different 
doses (10-30-90 g). 
Exploratory 
 
• 
To evaluate the cross clades reactivity determined by ICS 
2 weeks and/or 1 month after the second vaccination. 
• 
To evaluate the CD8+ T-cells immune response to the 
candidate vaccine F4co (p24-RT-Nef-p17) with or 

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without AS01B at three different doses (10-30-90 g). 
Study design 
• 
Experimental design: Single center, dose-escalating, 
staggered, parallel group study 
• 
Treatment allocation: Randomized for the adjuvantation 
(AS01B or water for injection) 
• 
Blinding: Partially blind: observer-blind for 
adjuvantation, open for antigen content 
• 
Treatment Groups: 
3 groups of 50 subjects receiving the candidate vaccine 
F4co (p24-RT-Nef-p17), adjuvanted with AS01B, 
respectively at 10, 30 or 90 g 
3 groups of 10 subjects receiving the candidate vaccine 
F4co (p24-RT-Nef-p17), non-adjuvanted, in water for 
injection, respectively at 10, 30 or 90 g 
• 
Vaccination schedule: 3 2 vaccinations administered 
intramuscularly according to a 0, 1, 6 month schedule 
(Amended September 24, 2007) 
• 
Controls: None 
• 
Type of study: Self-contained 
• 
Data collection: Remote data entry (RDE) 
• 
Duration of the study: The intended duration of the study, 
per subject will be approximately 14 months 
Number of subjects 
Target number of enrolled subjects = 180 (6 groups: 3 groups 
of 50 subjects and 3 groups of 10 subjects). 
 
Primary endpoints 
Reactogenicity and safety 
 
• 
Occurrence, intensity and relationship to vaccination of 
solicited local and general symptoms during a 7-day (Day 
0 to Day 6) follow-up period after each vaccination. 
• 
Occurrence, intensity and relationship to vaccination of 
unsolicited symptoms during a 30-day (Day 0 to Day 29) 
follow-up period after each vaccination. 
• 
Occurrence and relationship to vaccination of serious 
adverse events during the whole study period. 
• 
Haematological and biochemical levels at months 0, 1, 2, 
6, 7 9, 12 and at Day 44 (two weeks after the second 
vaccination) in all subjects. (Amended September 24, 
2007) 

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Immunogenicity 
 
• 
Frequency of CD4+ T cells expressing at least two 
cytokines including IL-2 equal or above the cut-off to at 
least 1, 2, 3 antigens and to all 4 antigens at Day 44 (two 
weeks after the second vaccination). 
Secondary endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T 
cells expressing IL-2 and/or TNF-and/or IFN-and/or 
CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T 
cells expressing at least 2 cytokines including IL-2 equal 
or above the cut-off at Months 0, 2, 6, 7, 12 and at Day 44 
(two weeks after the second vaccination). 
• 
Antibody titers to p17, p24, Nef, RT and F4co as 
measured by ELISA at Months 0, 2, 6, 7, 12 and at Day 
44 (two weeks after the second vaccination). (Amended 
September 24, 2007) 
Exploratory 
endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T 
cells to other HIV clades expressing IL-2 and/or TNF- 
and/or IFN-and/or CD40-L, as determined by ICS at 
Day 44 (two weeks after the second vaccination) and/or 
at Month 2. 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T 
cells expressing IL-2 and/or TNF-and/or IFN-and/or 
CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T 
cells expressing at least 2 cytokines (IL-2 and/or TNF- 
and/or IFN-and/or CD40-L) equal or above the cut-off 
at Months 0, 2, 6, 7, 12 and at Day 44 (two weeks after 
the second vaccination). (Amended September 24, 
2007) 

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TABLE OF CONTENTS 
 
PAGE 
SYNOPSIS ...........................................................................................................................4 
LIST OF ABBREVIATIONS ............................................................................................... 13 
GLOSSARY OF TERMS .................................................................................................... 16 
1. 
INTRODUCTION ........................................................................................................ 20 
1.1. 
Background .................................................................................................... 20 
1.1.1. 
Epidemiology and disease manifestation ....................................... 20 
1.1.2. 
The Human Immunodeficiency Virus-1 ........................................... 20 
1.1.3. 
Pathogenicity .................................................................................. 22 
1.1.4. 
Background to existing vaccine technology .................................... 22 
1.1.4.1. 
Role of anti-HIV antibodies ........................................... 23 
1.1.4.2. 
Role of Cell Mediated Immunity in HIV  
vaccines 
……………………………………………24 
1.1.4.3. 
Role of mucosal immune responses ............................ 25 
1.1.4.4. 
Role of adjuvants .......................................................... 25 
1.2. 
Rationale for the study ................................................................................... 26 
2. 
OBJECTIVES ............................................................................................................. 27 
2.1. 
Primary objectives .......................................................................................... 27 
2.2. 
Secondary objectives ..................................................................................... 27 
2.3. 
Exploratory objectives .................................................................................... 28 
3. 
STUDY DESIGN OVERVIEW ..................................................................................... 28 
4. 
STUDY COHORT........................................................................................................ 31 
4.1. 
Number of subjects / centers ........................................................................... 31 
4.2. 
Inclusion criteria .............................................................................................. 32 
4.3. 
Exclusion criteria for enrolment ...................................................................... 32 
4.4. 
Elimination criteria during the study ............................................................. 34 
4.5. 
Contraindications to subsequent vaccination ................................................. 35 
5. 
CONDUCT OF STUDY .............................................................................................. 35 
5.1. 
Ethics and regulatory considerations ............................................................. 35 
5.1.1. 
Institutional Review Board/Independent Ethics Committee  
(IRB/IEC) ......................................................................................... 36 
5.1.2. 
Informed consent ............................................................................ 37 
5.2. 
General study aspects ................................................................................... 39 
5.2.1. 
Study evaluations............................................................................ 39 
5.2.1.1. 
Behavioural risk assessment questionnaire ................. 39 
5.2.1.2. 
Clinical observations ..................................................... 40 
5.2.1.3. 
Diary Cards ................................................................... 40 
5.2.1.4. 
Laboratory parameters ................................................. 41 
5.2.1.5. 
Immunogenicity parameters ......................................... 41 
5.2.2. 
Detection of intercurrent HIV infection ............................................. 41 
5.3. 
Subject identification ...................................................................................... 43 
5.4. 
Outline of study procedures ........................................................................... 43 

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5.5. 
Detailed description of study stages/visits ...................................................... 46 
5.5.1. 
Screening Visit (Day -56 to Day -1) ................................................ 47 
5.5.2. 
Study Visit 1: First vaccination (Day 0 - Month 0) ........................... 47 
5.5.3. 
Follow-up Visit 1 (Day 7; for the 12 first vaccinated 
subjects only) .................................................................................. 48 
5.5.4. 
Study Visit 2: Second vaccination (Day 30 - Month 1) ................... 49 
5.5.5. 
Follow-up Visit 2 (Day 37; for the 12 first vaccinated 
subjects only) .................................................................................. 50 
5.5.6. 
Study Visit 3 (Day 44 - 2 weeks after second vaccination) ............. 50 
5.5.7. 
Study Visit 4 (Day 60 - Month 2) ..................................................... 50 
5.5.8. 
Study Visit 5: Third vaccination (Day 180 - Month 6) ..................... 51 
5.5.9. 
Follow-up Visit 5 (Day 187; in the first 12 vaccinated 
subjects only) .................................................................................. 52 
5.5.10. 
Study Visit 6 (Day 210 270- Month 7 9) ......................................... 52 
5.5.11. 
Study Visit 7 (Day 360 - Month 12) ................................................. 52 
5.6. 
Safety evaluation and processes for holding-on, stopping and/or 
restarting the trial ............................................................................................ 53 
5.6.1. 
Staggered design............................................................................ 53 
5.6.2. 
Review of safety data ..................................................................... 53 
5.6.3. 
Holding rules ................................................................................ 54 
5.6.4. 
Process for restarting vaccination/trial ............................................ 55 
5.6.5. 
Process for stopping of trial ............................................................ 55 
5.7. 
Sample handling and analysis ....................................................................... 55 
5.7.1. 
Treatment and storage of biological samples ................................. 55 
5.7.2. 
Laboratory assays ........................................................................ 55 
5.7.2.1. 
Virology .......................................................................... 55 
5.7.2.2. 
Biochemistry .................................................................. 56 
5.7.2.3. 
Haematology ................................................................. 56 
5.7.2.4. 
Urinalysis ....................................................................... 56 
5.7.3. 
Immunological read-outs ................................................................ 56 
5.7.3.1. 
Serology: antibody responses ..................................... 58 
5.7.3.2. 
Cell-mediated immune responses ............................... 58 
6. 
INVESTIGATIONAL PRODUCT AND ADMINISTRATION ........................................ 59 
6.1. 
Study vaccine .................................................................................................. 59 
6.2. 
Dosage and administration ............................................................................ 61 
6.2.1. 
Reconstitution of the F4co antigen with AS01B adjuvant ............... 61 
6.2.2. 
Reconstitution of the F4co antigen with water for injection 
(WFI)............................................................................................ 61 
6.2.3. 
Administration of reconstituted vaccine .......................................... 61 
6.3. 
Storage ............................................................................................................ 62 
6.4. 
Treatment allocation and randomization ........................................................ 62 
6.4.1. 
Randomization of supplies ............................................................. 63 
6.4.2. 
Randomization of subjects ............................................................. 63 
6.5. 
Method of blinding and breaking the study blind ............................................ 63 
6.6. 
Replacement of unusable vaccine ............................................................... 64 
6.7. 
Packaging....................................................................................................... 65 
6.8. 
Vaccine accountability ................................................................................. 65 
6.9. 
Concomitant medication/treatment ................................................................. 65 
7. 
HEALTH ECONOMICS ................................................................................................... 66 
7.1. 
Outcomes measurement and analysis ........................................................... 66 

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7.2. 
Economic data collection and analyses ......................................................... 66 
8. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ....................................... 66 
8.1. 
Definition of an adverse event ........................................................................ 66 
8.2. 
Definition of a serious adverse event ............................................................. 67 
8.3. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events and serious adverse events ............................. 68 
8.4. 
Time period, frequency, and method of detecting adverse events 
and serious adverse events ........................................................................... 68 
8.4.1. 
Solicited adverse events ................................................................. 69 
8.5. 
Evaluating adverse events and serious adverse events ................................ 71 
8.5.1. 
Assessment of intensity .................................................................. 71 
8.5.2. 
Assessment of causality ................................................................. 72 
8.5.3. 
Medically attended visits ................................................................. 73 
8.6. 
Follow-up of adverse events and serious adverse events and 
assessment of outcome ................................................................................. 73 
8.7. 
Prompt reporting of serious adverse events to GSK Biologicals .................... 75 
8.7.1. 
Time frames for submitting serious adverse event reports 
to GSK Biologicals .......................................................................... 75 
8.7.2. 
Completion and transmission of serious adverse event 
reports to GSK Biologicals .............................................................. 75 
8.8. 
Regulatory reporting requirements for serious adverse events ...................... 77 
8.9. 
Post-study adverse events and serious adverse events ................................ 77 
8.10. Pregnancy ...................................................................................................... 77 
8.11. Treatment of adverse events ......................................................................... 78 
9. 
SUBJECT COMPLETION AND WITHDRAWAL ...................................................... 78 
9.1. 
Subject completion ......................................................................................... 78 
9.2. 
Subject withdrawal.......................................................................................... 78 
9.2.1. 
Subject withdrawal from the study ................................................ 79 
9.2.2. 
Subject withdrawal from investigational product ............................. 79 
9.3. 
Screen and baseline failures .......................................................................... 80 
10. DATA EVALUATION: CRITERIA FOR EVALUATION OF OBJECTIVES ................. 80 
10.1. Primary endpoints .......................................................................................... 80 
10.2. Secondary endpoints ...................................................................................... 80 
10.3. Exploratory endpoints ..................................................................................... 81 
10.4. Estimated sample size ................................................................................... 81 
10.5. Study cohorts to be evaluated ....................................................................... 82 
10.6. Derived and transformed data ..................................................................... 83 
10.7. Final analyses ................................................................................................ 84 
10.7.1. 
Analysis of demographics/baseline characteristics ........................ 84 
10.7.2. 
Analysis of immunogenicity ............................................................ 84 
10.7.3. 
Analysis of safety ......................................................................... 85 
10.8. Planned interim analyses ............................................................................... 86 
11. ADMINISTRATIVE MATTERS .................................................................................... 87 
12. REFERENCES ............................................................................................................ 88 

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LIST OF TABLES 
 
PAGE 
 
Table 1 
Summary of the clinical trials conducted with the AS01B or the 
AS01E adjuvant .......................................................................................... 26 
 
Table 2 
Overview of diary cards .......................................................................... 41 
 
Table 3 
List of study procedures .............................................................................44 
 
Table 4 
Intervals between study visits .................................................................... 46 
 
Table 5 
Immunological read-outs (characteristics of the assays) ........................... 57 
 
Table 6 
Immunological read-outs (timings, markers, numbers of subjects 
and laboratory) ...........................................................................................57 
 
Table 7 
Composition of the study vaccines ............................................................ 60 
 
Table 8 
Solicited local adverse events ................................................................... 70 
 
Table 9 
Solicited general adverse events ................................................................70 
 
Table 10 
Intensity scales for solicited symptoms...................................................... 71 
 
Table 11 
Precision achieved for different estimated proportions and for the 
two sample sizes of 10 and 50 subjects [by PASS 2005, 95% 
confidence interval of a proportion] ........................................................... 81 
 
Table 12 
Difference between 2 groups of 50 subjects that can be detected 
with a power of 80% (two-sided alpha of 0.0167 for multiple 
comparisons between three groups) (by PASS 2005, two 
independent proportions, Fisher's Exact test) ........................................... 82 
 
LIST OF FIGURES 
 
PAGE 
Figure 1 
Overall study design overview .................................................................... 29 
Figure 2 
Staggered design overview ........................................................................29 

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APPENDICES 
 
PAGE 
Appendix A 
World Medical Association Declaration of Helsinki.................................... 91 
Appendix B 
Administrative Matters ............................................................................... 95 
Appendix C 
Overview of the Recruitment Plan ........................................................... 101 
Appendix D 
Handling of Biological Samples Collected by the Investigator ................. 102 
Appendix E 
Shipment of Biological Samples .............................................................. 106 
Appendix F 
Laboratory Assays ................................................................................... 108 
Appendix G 
Vaccine supplies, packaging and accountability ..................................... 109 
Appendix H 
Detection of intercurrent HIV-1 infection ................................................. 111 
Appendix I 
Amendments and Administrative Changes to the Protocol ..................... 112 

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List of Abbreviations 
g 
Microgram 
 
3D-MPL 
3 Deacylated Monophosphoryl Lipid A 
 
ADCC 
Antibody-Dependent Cell-mediated Cytotoxicity 
 
AE 
Adverse event 
 
AIDS 
Acquired Immunodeficiency Syndrome 
 
ALT 
Alanine Aminotransferase 
 
AS0x 
GlaxoSmithKline Adjuvant System x 
 
AST 
Aspartate Aminotransferase 
 
ATP 
According To Protocol 
 
CD4 (8, 40L) 
Immune cells that carry a marker on its surface known as 
Cluster of Differentiation 4 (8, 40L) 
 
CDM 
Clinical Development Manager 
 
CEVAC 
Center for Vaccinology, Ghent University, Belgium 
 
CI 
Confidence Interval 
 
CMI 
Cell-Mediated Immunity 
 
CSC 
Central Study Coordinator 
 
CTL 
Cytotoxic T Lymphocyte 
 
DNA 
Deoxyribonucleic Acid 
 
eCRF 
Electronic Case Report Form 
 
ELISA 
Enzyme Linked Immunosorbent Assay 
 
GCP 
Good Clinical Practice 
 
GMC 
Geometric Mean Concentration 
 
GMT 
Geometric Mean Titer 
 
GSB 
Global Safety Board 
 
GSK 
GlaxoSmithKline 

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HCG 
Human Chorionic Gonadotropin 
 
HIV 
Human Immunodeficiency Virus 
 
IB 
Investigator's Brochure 
 
ICF 
Informed Consent Form 
 
ICS 
Intracellular Cytokine Staining 
 
IDMS 
Internal Data Monitoring Committee 
 
IEC 
Independent Ethics Committee 
 
IFN- 
Interferon gamma 
 
IL-2 
Interleukin 2 
 
IN 
Integrase 
 
IRB 
Institutional Review Board 
 
ISCOMS 
Immunostimulating Complexes 
 
LTR 
Long Terminal Repeat 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
mL 
Millilitre 
 
mm3 
Cubic millimetre 
 
MVA 
Modified Vaccinia virus Ankara 
 
PBMC 
Peripheral Blood Mononuclear Cell 
 
PCV 
Packed Cell Volume 
 
PID 
Subject Identification number 
 
PR 
Protease 
 
QS21 
Quillaja Saponaria 21: a triterpene glycoside purified 
from the bark of Quillaja saponaria 
 
RBC 
Red Blood Cell 
 
RDE 
Remote Data Entry 
 
RNA 
Ribonucleic Acid 

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RT 
Reverse Transcriptase 
 
SAE 
Serious Adverse Event 
 
SBIR 
Central randomization call-in on internet 
 
SHIV 
A chimeric virus composed of an HIV envelope and SIV 
nucleocaspid and replication machinery 
 
SIV 
Simian Immunodeficiency Virus 
 
SOP 
Standard Operating Procedure 
 
SRT 
Safety Review Team 
 
STD 
Sexually Transmitted Disease 
 
TNF- 
Tumour necrosis factor alpha 
 
UNAIDS 
Joint United Nations Programme on HIV1AIDS 
 
VRC 
Vaccine Research Center 
 
VSMB 
GSK Vaccine Safety Monitoring Board 
 
WBC 
White Blood Cell 
 
WFI 
Water For Injection 
 
WHO 
World Health Organization 

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Glossary of Terms 
Adverse event: 
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. 
 
An AE can therefore be any unfavourable and unintended 
sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
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. 
 
Azoospermia 
Documented azoospermia refers to the outcome of the 
investigator's/designee's medical examination of the 
subject or review of the subject's medical history for 
study eligibility, as obtained via a verbal interview with 
the subject or from the subject's medical records. 
 
Blinding: 
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. In a single- 
blind trial, the investigator and/or his staff are aware of 
the treatment assignment but the subject is not. In an 
observer-blind study, the subject and the study personnel 
involved in the clinical evaluation of the subjects are 
blinded while other study personnel may be aware of the 
treatment allocation. When the investigator and sponsor 
staff who are involved in the treatment or clinical 
evaluation of the subjects and review/analysis of data are 
also unaware of the treatment assignments, the study is 
double blind. Partially blind is to be used for study 
designs with different blinding levels between different 
groups, e.g. double blinded consistency lots which are 
open with respect to the control group. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. 
 
Central Study 
Co-ordinator: 
An individual assigned by and centrally located at GSK 
Biologicals at Rixensart who is responsible for assuring 
proper conduct of a clinical study. 

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Contraception 
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly (when applicable, as 
mentioned in the product label) for example abstinence, 
combined or progestogen oral contraceptives, injectable 
progestogen, implants of levonorgestrel, oestrogenic 
vaginal ring, percutaneous contraceptive patches or 
intrauterine device (IUD) or intrauterine system (IUS), 
vasectomy with documented azoospermia of the sole 
male partner or double barrier method (condom or 
occlusive cap plus spermicidal agent). 
 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
 
eTrack 
GSK's clinical trials tracking tool 
 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis (see 
Sections 4 and 10.5 for details on criteria for 
evaluability). 
 
Investigational product: 
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, 
including a product with a marketing authorization when 
used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain 
further information about an approved use. 
 
Medical Monitor: 
An individual medically qualified to assume the 
responsibilities of the sponsor (GSK Biologicals) 
especially in regards to the ethics, clinical safety of a 
study and the assessment of adverse events. 
 
Post-menopause 
Menopause is the age associated with complete cessation 
of menstrual cycles, menses, and implies the loss of 
reproductive potential by ovarian failure. A practical 
definition accepts menopause after one year without 
menses with an appropriate clinical profile at the 
appropriate age, e.g. > 45 years. 

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Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study. 
N.B. ny change that falls under the definition of a 
protocol amendment (e.g. a change that affects the safety 
of subjects, scope of the investigation, study design, or 
scientific integrity of the study) MUST be prepared as an 
amendment to the protocol. 
 
Protocol amendment: 
ICH defines a protocol amendment as: "A written 
description of a change(s) to or formal clarification of a 
protocol." GSK Biologicals further details this to include 
a change to an approved protocol that affects the safety of 
subjects, scope of the investigation, study design, or 
scientific integrity of the study. 
 
Randomization: 
Process of random attribution of treatment to subjects in 
order to reduce bias of selection 
 
Site Monitor: 
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites. 
 
Solicited adverse event: 
Adverse events (AEs) to be recorded as endpoints in the 
clinical study. The presence/occurrence/intensityof  these 
events is actively solicited from the subject or an observer 
during a specified post-vaccination follow-up period. 
 
Study Monitor: 
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of a clinical study. 
 
Subject number: 
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study. 
 
Subject: 
Term used throughout the protocol to denote an 
individual that has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the investigational product(s) or as a control. 
 
Treatment number: 
A unique number identifying a treatment to a subject, 
according to the study randomization or treatment 
allocation. 
 
Treatment: 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject, 
identified by a unique number, according to the study 
randomization or treatment allocation. 

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Unsolicited adverse 
event: 
Any adverse event (AE) reported in addition to those 
solicited during the clinical study. Also any "solicited" 
symptom with onset outside the specified period of 
follow-up for solicited symptoms will be reported as an 
unsolicited adverse event. 

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1. 
INTRODUCTION 
 
1.1. 
Background 
 
1.1.1. 
Epidemiology and disease manifestation 
 
Since the first clinical evidence was reported in 1981, HIV has continued its relentless 
spread and today it is estimated that around 40 million people are living with HIV/AIDS 
in the world, and that more than 20 million people have already died from the disease 
[WHO, 2005]. Of the estimated 40 million people living with HIV/AIDS in the world, 
95% of them lives in developing countries, especially in Africa, which is home to 26 
million people already infected with HIV. In at least six Sub-Saharan African countries, 
one in five adults are already infected with HIV, and in another ten countries, 10% of 
adults are infected. HIV continues to spread relentlessly at a rate of 14,000 new HIV 
infections every day. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has 
forecasted that from now until 2010, we could be adding some 5 million new infections 
every year [WHO, 2005; Esparza, 2005; Excler, 2005]. 
 
1.1.2. 
The Human Immunodeficiency Virus-1 
 
The Human Immunodeficiency Virus-1 (HIV-1), causative agent of AIDS, is a member 
of the lentivirus group of retroviruses. Retroviruses have the unique ability to transcribe 
their RNA to DNA, and are capable of integrating their genome into the host cell DNA 
early in infection. They achieve this feat with the aid of the reverse transcriptase enzyme 
they encode. The retroviruses also show strong cell-cycle dependence for productive 
infection requiring therefore proliferating cells for infection. However, the lentivirus HIV 
is not dependent on host cell mitosis for establishment of provirus. Thus, non-dividing 
cells such as primary macrophages, follicular dendritic cells and microglial cells sustain a 
productive replication cycle in the absence of cell division, with the exception of 
quiescent T lymphocytes which are refractory to HIV replication [Stevenson, 1995]. 
 
The HIV-1 virion is spherical consisting essentially of an inner electron-dense core and 
an outer envelope [Gelderblom, 1987; Hockley, 1988]. Three major genes are found in 
the viral genome, gag, pol and env. They are flanked on both sides by identical 
sequences, long terminal repeats (LTR). The LTRs contain cis-acting elements with 
signals for viral integration, transcription and RNA synthesis. Additional open reading 
frames that flank the env gene encode several regulatory proteins including Vif, Vpr, Tat, 
Rev, Vpu and Nef. They have important functions during the early stages of the viral life 
cycle and are essential for efficient viral replication. 
 
The env gene encodes the outer membrane protein gp120, and the transmembrane 
glycoprotein gp41. Gp41 is responsible for virus attachment to the host cell during 
infection. Gp120 binds to the major binding receptor, CD4, on CD4+ cells; chemokine 
receptors CCR5 and CXCR4 act as coreceptors. Gp120 contains five variable and five 
conserved regions; one variable region, the V3 loop, contains the principal neutralizing 
determinant of HIV-1. Gp120 contains other variable and conserved neutralizing epitopes 

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and cytotoxic T-lymphocyte (CTL) epitopes. Gp120 and gp 41 form trimers on the 
surface of the mature virion. 
 
The gag gene encodes the 4 Gag proteins, MA or p17, a matrix protein, CA or p24, the 
viral capsid and NC or p6 and p7, the nucleocapsid proteins. These structural proteins 
make up the core of the virion. 
 
The pol gene encodes the viral enzymes, the most important of which are reverse 
transcriptase (RT), protease (PR) and integrase (IN). RT transcribes the viral RNA into 
double-stranded DNA. IN integrates the DNA produced by RT into the host's genome. 
PR is an enzyme that cuts proteins, issued from gag and pol, into separate functional 
units. 
 
The Nef regulatory protein accumulates before Tat in newly infected cells and acts as a 
crucial determinant of HIV virulence. The Nef protein is believed to be involved in the 
modulation of CD4 expression by triggering the rapid endocytosis and lysosomal 
degradation of this main virus receptor. The Nef protein may disrupt T-lymphocyte 
function and signalling as a result of its interaction with critical signal transduction 
components. 
 
Analyses of nucleic acid from the HIV-1 have revealed large amounts of variation both 
within and between patients. The extensive genetic variability of HIV is primarily due to 
the high error rates of the viral reverse transcriptase, with deletions and insertions 
occurring in addition to substitutions. Viral genetic variability occurs between 
geographical regions, mainly due to differential geographic distribution of the multiple 
genetic subtypes of HIV-1, with documented genetic variability in the env gene in excess 
of 30% [Myers, 1994; WHO, 1994; Delwart, 1994; Weniger, 1994]. Furthermore, 
genomic recombination between two different HIV-1 populations frequently occurs in 
vivo resulting in genetic shifts [Peeters, 2000]. With the continuous evolution and mixing 
of genetic subtypes and the reality of recombination, new vaccine strategies capable of 
coping with the possibility of antigenic shift will be needed. 
 
Genetic variability is a major characteristic of HIV-1 [Thomson, 2005]. Different HIV-1 
strains fall into 3 groups: group M (major), group O (for 'outliers'), and group N (non- 
M/non-O). Group M viruses are the most common globally and are further subdivided 
into different genetic subtypes or clades. Ten clades have been identified to date, 
designated A--E, F--H, J, and K. The genetic subtypes E is the predominant group of 
viruses involved in heterosexual transmission in Thailand [Alaeus, 2000; Thomson, 
2002]. Genetic subtype B is the dominant subtype in North America, Brazil, The 
Caribbean, Australia and Europe, and is the most studied of all genetic subtypes [Alaeus, 
2000; Osmanov, 2002] representing 12.3% of all HIV-1 infections worldwide. Clade C is 
the most prevalent clade worldwide, responsible for more than 47% of infections. South 
East Asia is dominated by clade C, but the clade E is also important, especially in 
Thailand. In South East and South Africa, subtype C predominates [Osmanov, 2002; 
Esparza, 2000]. In East Africa subtypes A and D dominates. In West Africa, CRF AG is 
dominant with a low frequency of group O viruses [Alaeus, 2000]. 

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1.1.3. 
Pathogenicity 
 
There are a number of immunological features of HIV pathogenicity that makes HIV 
vaccine development a challenging task. There is a high probability that antibodies and T 
cells select successive immunological variants of the virus which continue to evade the 
host response. There is evidence for the existence of specific immunity following natural 
infection, and the virus is held in check by the host immune response, often for many 
years, until the immune system is finally incapable of containing the virus. During the 
course of infection with HIV, cellular immune responses (helper and specific cytotoxic T 
cells) as well as binding antibodies, virus neutralization, and antibody-dependent cell 
mediated cytotoxicity (ADCC) can be detected [Letvin, 1993; Weiss, 1993]. 
 
1.1.4. 
Background to existing vaccine technology 
 
The main scientific obstacles to the development of an efficacious AIDS vaccine can be 
summarized as follows [Excler, 2005]: 
 
• 
Antigenic diversity and hypervariability of the virus 
• 
Transmission of disease by mucosal route 
• 
Transmission of the virus by infected cells 
• 
Resistance of wild type virus to seroneutralization 
• 
Integration of the virus genome into the host cell chromosomes 
• 
Latency of the virus in resting memory T-cells 
• 
Rapid emergence of viral escape mutants in the host 
• 
Downregulation of MHC class I antigens 
As mentioned above, the development of an AIDS vaccine remains an important goal in 
the global effort to control the HIV epidemic. Unfortunately, even more than 20 years 
after the discovery of HIV-1, there are very few promising candidate vaccines in late 
stages of development, and the first phase III trials based on VaxGen's AIDSVAX have 
failed to demonstrate significant efficacy against virus infection [McCarthy, 2003]. There 
is one ongoing phase III trial in Thailand that combines the AIDSVAX product with an 
ALVAC canarypox vector, but the chances of demonstrating vaccine efficacy are 
considered low [Joseph, 2005]. 
The most desirable goal for novel HIV vaccine approaches is the prevention of virus 
infection through induction of neutralising antibodies. The principal target for such 
antibodies is the envelope glycoprotein of HIV. In fact, it has been demonstrated in the 
past that immunization with monomeric gp120 elicited neutralizing antibodies that were 
able to protect non-human primates from homologous virus infection after challenge with 
HIV or chimeric SHIV. However, since the principal neutralizing domain on gp120 is 
highly variable (V3 loop), this protection is generally narrow and strain-specific. 
Therefore, a broadly effective vaccine based on a conventional gp120 immunogen is not 
considered promising and recent data from VaxGen's phase III trials with gp120 have 
reinforced this view. Several strategies are being pursued to generate improved envelope 

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immunogens that would induce more meaningful antibodies, but to date none of these 
approaches has generated entirely convincing results and/or is being investigated in 
clinical trials. 
A different and potentially more feasible aim is the control of virus load in the infected 
host using an HIV vaccine that induces cell-mediated immunity against conserved 
epitopes. CD8-positive cells are the main immune effector mechanism for the elimination 
of virus-infected cells. It has been demonstrated in the SIV monkey model that 
experimental depletion of CD8 cells leads to the loss of control of an established virus 
infection. However, it has also been demonstrated that the CD8 effector cells are subject 
to immune escape. Therefore, CD8 responses should be directed against as many 
conserved epitopes as possible. 
Several new technologies are being developed for the induction of HIV-specific CD8 T 
cells. These technologies include numerous plasmid DNA-based approaches and a 
number of different viral and bacterial vectors. Phase I clinical immunogenicity data are 
available for DNA vaccines from the NIH Vaccine Research Center (VRC) and the 
Oxford University group [Cebere, 2006; Estcourt, 2004], demonstrating only marginal 
immunogenicity. The best DNA vaccine to date has been developed by Merck, but the 
phase I data indicate inferiority to the adenovirus 5 (Ad5) technology. Phase I data also 
exist for three novel poxvirus vectors. NYVAC from the EuroVacc consortium, Fowlpox 
from Virax, and a modified vaccinia virus Ankara (MVA) from the McMichael group 
have yielded unconvincing results in terms of CD8 T cell induction. A different MVA 
from Bavarian Nordic appears more potent in preliminary phase I trials in uninfected 
volunteers and in HIV-infected individuals. The most convincing CD8 T cell-inducing 
technology seems to be Ad5 (Merck), which has been evaluated alone and in combination 
with DNA. It represents the first adenovirus-based vaccine that is being tested in large 
phase IIb proof-of-concept trials. 
A fair number of additional vector technologies have reached or will reach the clinic in 
the coming years. The first alphavirus-based vector (VEE from Alphavax) is currently 
being evaluated in a phase I trial in the US and South Africa. Other alphavirus-based 
approaches are at the pre-clinical stage (SFV from Bioption, Sindbis from Chiron). 
Alternative adenovirus vectors are at the pre-clinical stage (notably human Ad11 and 
Ad35, Ad5 chimeras, as well as nonhuman primate adenos). A negative strand RNA virus 
vector (VSV) has been developed by Wyeth, and a recombinant measles vector is being 
pursued by the Pasteur Institute and GSK. Several DNA vaccine approaches are at the 
pre-clinical level [Spearman, 2006]. 
 
1.1.4.1. 
Role of anti-HIV antibodies 
 
Antibodies against viral pathogens usually play a critical role in preventing infection, and 
this is also true for HIV. The principal antibody responses comprise neutralizing 
antibodies and antibodies that mediate ADCC. Both types of antibodies are directed 
against the viral Env protein. 
 
Vaccine studies in primate models have revealed that neutralizing antibodies correlated 
with protection from cell-free intravenous infection with homologous virus strains 
[Mooij, 2002]. Recently passive immunization studies with a synergistic combination of 

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three broadly neutralizing antibodies in Rhesus monkeys have demonstrated that N Ab 
alone can protect from heterologous and pathogenic virus challenge by different mucosal 
routes [Mooij, 2002]. However, it has not been possible to generate similar broad 
responses by active immunization with envelope protein. This has been a major drawback 
for env-based HIV vaccines, since they afford only very narrow protection against virus 
strains that resemble closely the vaccine antigen. 
 
The difficulty in inducing effective neutralizing antibodies to HIV-1 is predominantly a 
reflection of the enormous variation in the envelope protein and the failure of most 
antibodies that recognize this protein to neutralize the virus. It is therefore generally 
accepted that a combination of both humoral and cell mediated immune responses may be 
needed for effective protection, with potentially further improvement on addition of a 
mucosal immune component [Joseph, 2005]. 
 
1.1.4.2. 
Role of Cell Mediated Immunity in HIV vaccines 
 
The role of CD8+ T cell responses in prophylactic HIV vaccine protection has become 
more evident in recent years. It has been demonstrated in the simian immunodeficiency 
virus (SIV) model that CD8+ cytotoxic T lymphocytes (CTLs) play a role in protection 
from high virus load and disease. These observations have been extended to the SHIV 
model using SHIV89.6p [Mooij, 2002; Reimann, 1996]. 
 
The beneficial effect of both HIV-specific CD4+ and CD8+ T-cell responses in 
seropositive individuals has been demonstrated in a number of studies [Johnson, 1998]. 
In addition to direct cytotoxic activity, chemokines and suppressor factors are released 
from CD8+ T-cells with subsequent inhibition of viral replication in vitro. CD8+ CTL 
responses following primary infection are associated with the control of viral replication 
during acute infection. Furthermore, strong CTL responses are observed in long-term 
non-progressors [Rinaldo, 1995] and in highly-exposed, seronegative African sex 
workers [Rowland-Jones, 1995]. In chronically infected individuals, a significant inverse 
correlation was established between HIV-specific CTL frequency and plasma RNA level 
[Ogg, 1998]. The protective role of CTL was further substantiated by the characterisation 
of virus mutants escaping CTL recognition [Borrow, 1997]. 
 
Furthermore, polyclonal, persistent, vigorous CD4+ T-cell proliferative responses have 
been found to be associated with the control of viremia and proliferative responses to 
recombinant p24 were found to be inversely related to viral load [Rosenberg, 1997]. In 
addition to providing help to B-cell and CD8+ T-cells, these CD4+ T-cells are necessary 
to maintain HIV-specific CTL memory. Following antigenic stimulation CD4+ T-cells 
may also provide viral interference by secretion of cytokines and chemokines. 
 
Despite accumulating evidence that CD8+ T cells contribute significantly to the control 
of the virus, viral escape following a single point mutation in a CTL epitope has resulted 
in the death of a monkey that was protected by a DNA vaccine expressing gag and env 
[Barouch, 2002]. 

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1.1.4.3. 
Role of mucosal immune responses 
 
Although still in its infancy, preclinical studies with vaccines designed to elicit mucosal 
immunity and block sexual transmission have demonstrated the induction of protective 
mucosal immunity in the macaque and chimpanzee [Lehner, 1996; Benson, 1998; Girard, 
1996]. 
 
1.1.4.4. 
Role of adjuvants 
 
Adjuvants can enhance the immune response to HIV vaccines by improving delivery of 
the antigen, selecting the immune response and decreasing the number of immunizations. 
 
Due to the modulation by adjuvants of antigen presentation, vaccines are able to elicit 
both T-helper cells and CTLs. The major histocompatibility complex (MHC) class I 
restricted T cell immune response usually occurring in response to intracellular 
pathogens, such as viruses, leading to CTL activity is, however, not generally observed 
with protein or peptide antigens. There is evidence that presence of immunostimulating 
complexes (ISCOMS) or QS-21 can elicit CTL activity with protein, peptides or 
inactivated viruses [Le, 2001; Vandepapeliere, 2005]. Addition of such 
immunostimulants is therefore an important step in the development of a protein based 
HIV-1 vaccine in order to induce or augment the activation of cell-mediated immune 
response. 
 
Seven clinical studies have been performed with the AS01B adjuvant (liposome-based 
formulation containing the immunostimulants 3D-MPL [3-deacylated monophosphoryl 
lipid A] and QS21 [a triterpene glycoside purified from the bark of Quillaja saponaria]) 
formulated with various antigens. A total of 450 adult or elderly subjects have received 
between 1 and 4 doses of vaccines containing AS01B adjuvant. Fifty children and 75 
elderly subjects have received 1 dose of the AS01E adjuvant (contains half the 
concentrations of MPL and QS-21 but in the same volume as AS01B). Table 1 
summarizes the clinical trials in which AS01B or AS01E has been used. For more details, 
please refer to the Investigator's Brochure. 

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Table 1 
Summary of the clinical trials conducted with the AS01B or the 
AS01E adjuvant 
 
Study No. 
(Status) 
Study Design 
Age 
Number 
subjects 
Number 
injections 
Adjuvant 
Antigens 
Th-Adj-005, 
Concluded 
Double-blind, 
randomized, 
safety/immuno 
18-40 
years 
50 
3 
AS01B 
HBsAg 
HIV-002, 
Concluded 
Double-blind, 
randomized, 
safety/immuno 
18-50 
years 
60 
4 
AS01B 
gp120/NefTat 
EXPLO-CRD- Open, randomized, 
18-30 
20 
2 
AS01B 
gE 
004, 
safety/immuno 
50-70 
90 
Concluded 
years 
Malaria-027, 
Completed 
Double-blind, 
randomized, 
efficacy, 
safety/immuno 
18-45 
years 
50 
3 
AS01B 
RTS,S 
Malaria-044, 
Concluded 
Double-blind, 
randomized, 
safety/immuno 
18-35 
years 
85 
3 
AS01B 
RTS,S 
Malaria-046, 
Concluded 
Double-blind, 
randomized, 
safety/immuno 
18 months 
- 4 years 
50 
3 
AS01E 
RTS,S 
Malaria-051, 
Ongoing 
Double-blind, 
randomized, 
efficacy 
18- 50 
years 
20 
3 
AS01B 
LSA-1 
FluAS25-003, Open, randomized, 
65 years 75 
1 
AS01B 
A/New Caledonia/20/99 
Completed 
safety/immuno 
75 
1 
AS01E 
A/New York/55/2004 
B/Jiangsu/10/2003 
HBsAg : Hepatitis B surface antigen 
RTS,S: CS antigen with HBsAg 
gp120/NefTat: HIV antigens 
gE: glycoprotein E - Varicella Zoster Virus (VZV) antigen 
Concluded -study completed but analysis not completed 
 
 
1.2. 
Rationale for the study 
 
The most prominent immune effector mechanisms directed against HIV are neutralizing 
antibodies and CD8+ T cells. In addition, accumulating evidence suggests that CD4+ T 
cells, which provide essential help to the other compartments of an adaptive immune 
response, are equally crucial for the induction of effective HIV immunity. In particular, 
the analysis of immune responses in HIV-infected individuals suggests a crucial role for 
CD4+ T cells. It appears that CD4+ cells provide essential help to CD8+ effector cells in 
long-term non-progressors. In contrast, the absence of HIV-specific CD4+ T cells in 
chronically infected individuals seems to be related to an impairment of CD8+ T cell 
maturation into effector cells. Thus, it appears that in order to maintain functional CD8+ 
T cell immunity, strong and broad CD4+ T cell responses are required and that these 
responses should be induced by an effective HIV vaccine. 
 
Probably the most potent approach to induction of CD4+ T cell responses is the use of 
adjuvanted protein vaccines. Indeed, GSK's previous candidate HIV vaccines consisted 

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of two recombinant proteins, gp120 and NefTat, which were formulated in potent 
proprietary adjuvants (AS01B, AS02A and AS02V). These vaccines were shown to 
induce very potent CD4+ T cell responses in two independent clinical trials (HVTN-041 
and HIV-002). The gp120 antigen was the most immunogenic vaccine component, and 
the Nef and Tat-directed responses were lower in comparison. 
 
AS01B (liposome-based formulation containing the immunostimulants 3D-MPL [3- 
deacylated monophosphoryl lipid A] and QS21 [a triterpene glycoside purified from the 
bark of Quillaja saponaria]) was chosen among other potent proprietary adjuvants, from 
several clinical studies (for exhaustive details please refer to the Investigator's Brochure) 
for its propensity to induce a stronger Th1 cellular-mediated immune response and its 
acceptable safety profile. 
 
Since such CD4+ cell responses need to cover the broadest possible spectrum of 
circulating HIV strains, an HIV vaccine should contain many different CD4 epitopes 
from different viral proteins. It was therefore desirable to include well-conserved and 
highly immunogenic HIV antigens in an improved vaccine formulation. The viral 
antigens that contain the highest number of conserved T cell epitopes are Gag, Pol, and 
Nef. Consequently, GSK chose to include these antigens as a single fusion protein (F4co) 
into an adjuvanted (AS01B) vaccine formulation. 
 
Please refer to the Investigator's Brochure for a review of the pre-clinical studies of the 
F4co (p24-RT-Nef-p17) candidate vaccine and for exhaustive details concerning clinical 
studies conducted with gp1201NefTat (HVTN-041 and HIV-002) and1or AS01B (HIV- 
002 and TH-ADJ-005). 
 
2. 
OBJECTIVES 
 
2.1. 
Primary objectives 
 
• 
To evaluate the reactogenicity and safety of the candidate vaccine F4co (p24-RT- 
Nef-p17) with or without AS01B adjuvant at three different doses (10-30-90 g). 
• 
To evaluate the CD4+ T-cell response to the candidate vaccine F4co (p24-RT-Nef- 
p17) with or without AS01B at three different doses (10-30-90 g) in terms of 
proportion of responders to at least 1, 2, 3 antigens and to all 4 antigens determined 
two weeks after the second vaccination. 
Refer to Section 10.1 for definition of primary endpoints. 
 
2.2. 
Secondary  objectives 
 
• 
To evaluate the CD4+ T-cell immune response to the candidate vaccine F4co (p24- 
RT-Nef-p17) with or without AS01B at three different doses (10-30-90 g) after two 
and three vaccinations. (Amended September 24, 2007) 

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• 
To evaluate the serological response to the candidate vaccine F4co (p24-RT-Nef- 
p17) with or without AS01B at three different doses (10-30-90 g) after two and 
three vaccinations.(Amended September 24, 2007) 
• 
To evaluate the persistence of cell-mediated and serological responses to the 
candidate vaccine F4co (p24-RT-Nef-p17) with or without AS01B at three different 
doses (10-30-90 g). 
Refer to Section 10.2 for definitions of secondary endpoints. 
 
2.3. 
Exploratory  objectives 
 
• 
To evaluate the cross clades reactivity determined by ICS 2 weeks and/or 1 month 
after the second vaccination. 
• 
To evaluate the CD8+ T-cells immune response to the candidate vaccine F4co (p24- 
RT-Nef-p17) with or without AS01B at three different doses (10-30-90 g). 
Refer to Section 10.3 for definitions of exploratory endpoints. 
 
3. 
STUDY DESIGN OVERVIEW 
 
Treatment 
Dose 
(g) 
Adjuvant 
AS01B 
(Number of subjects) 
(
Water for injection 
(WFI) 
Number of subjects) 
F4co (p24-RT-Nef-p17) 
10 
50 
10 
F4co (p24-RT-Nef-p17) 
30 
50 
10 
F4co (p24-RT-Nef-p17) 
90 
50 
10 

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Screening 
Screening 
visit 
Day -56 to -1 
Blood sample 
Visit 1 
Day 0 
Randomization 
Vaccination 
Blood 
sample 
Figure 1 
Overall study design overview 
 
F4 (10 µg) + AS01B (N = 50) 
F4 (10 µg) + WFI (N = 10) 
F4 (30 µg) + AS01B (N = 50) 
F4 (30 µg) + WFI (N = 10) 
F4 (90 µg) + AS01B (N = 50) 
F4 (90 µg) + WFI (N = 10) 
 
 
Study conclusion 
 
 
Vis 
Da 
Vaccn 
Blo 
sa 
 
Visit 3 
Day 44 
Blood 
sample 
 
Visit 4 
Day 60 
Blood 
sample 
 
Vis 
Day 
 Vacci 
Blo  
sa 
 
Follow-up 
visit 1 
Day 7* 
 
* For the 12 first vaccinated subjects only at each of the 3 vaccine doses (10, 30 and 90 µg) 
(Amended September 24, 2007) 
 
Figure 2 
Staggered design overview 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Amended September 24, 2007) 
it 2 
y 30 
i ation 
d 
ple 
Follow-up 
visit 2 
Day 37* 
it 5 
180 
nation 
d 
mple 
Visit 6 
Visit 7 
Day 210 
Day 360 
Day 270 
Blood 
Blood 
sample 
sample 
 Follow-up 
 visit 5   
 Day 187* 

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Each vaccination in each dose group will be administered to the first 12 subjects at the 
rate of maximum 1 subject per day during the first 5 working days. After that period, 
provided stopping rules do not apply, the rate of vaccination will be unlimited. 
 
* Holding rules = vaccinations will be put on hold if at least 3 out of the 12 subjects 
develop a Grade 3 general solicited AE, during the 7-day follow-up period after 
vaccination which persists at Grade 3 for more than 48 hours and which is considered to 
be related to vaccination or if at least 4 out of the 12 subjects develop any other Grade 3 
unsolicited AE considered to be related to vaccination during the 7-day follow-up period 
after vaccination or if at least 4 out of the 12 subjects develop any Grade 3 general 
solicited (persisting at Grade 3 for more than 48 hours and considered related to 
vaccination) or unsolicited AE (considered related to vaccination) during the 7-day 
follow-up period after vaccination or at least one life threatening vaccine related SAE 
occurs or at least one subject shows ulceration (necrosis of the dermis) at the injection 
site following vaccination. The same approach will be repeated with each of the three 
vaccine doses (10, 30 and 90 g) and for each of the three two vaccinations (see Section 
5.6.3).(Amended September 24, 2007) 
 
• 
Experimental design: Single center, dose-escalating, staggered, parallel-group study 
with 6 groups (Figure 1 and Figure 2): 
3 groups of 50 subjects receiving the candidate vaccine F4co (p24-RT-Nef-p17), 
adjuvanted with AS01B, respectively at 10, 30 or 90 g. 
3 groups of 10 subjects receiving the candidate vaccine F4co (p24-RT-Nef-p17), 
non-adjuvanted, in water for injection, respectively at 10, 30 or 90 g. 
• 
Control groups: None. 
• 
Vaccination process: A staggered dose-escalation design will be used for safety 
reasons. A first group of 12 subjects (10 receiving the adjuvanted vaccine and 2 
receiving the vaccine in WFI) will be enrolled to receive their first vaccination at the 
lowest dose (10 g), at a rate of maximum 1 subject per day during the first 5 
working days. Provided no safety issues leading to clinical hold or stop occurred 
(Figure 2), the 12 subjects will be allowed to receive their second vaccination on Day 
30, according to the same rate (1 subject/day during the first 5 working days). The 
remaining subjects of the same dose group (N=48) will receive their first 
vaccination. Then, a new group of 12 subjects will be enrolled to receive their first 
vaccination at the medium dose (30 g) at a rate of maximum 1 subject per day 
during the first 5 working days. Provided no safety issues leading to clinical hold or 
stop occurred, subjects will be allowed to receive their second vaccination on Day 30 
at the same rate, the remaining subjects (N=48) of the same dose group will receive 
their first vaccination. Then, a new group of 12 subjects will be enrolled to receive 
their first vaccination at the highest dose (90 g) at a rate of maximum 1 subject per 
day during the first 5 working days. Provided no safety issues leading to clinical hold 
or stop occurred, subjects will be allowed to receive their second vaccination on Day 
30 at the rate of maximum 1 subject per day during the first 5 working days and the 
remaining subjects (N=48) of the same dose group will receive their first 
vaccination. Exactly the same methodological approach will be replicated for the 

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third vaccination in each dose group (see Section 5.6.3).(Amended September 24, 
2007) 
• 
Blinding: Partially blind: observer-blind for adjuvantation, open for antigen content 
• 
Treatment allocation: Randomized for the adjuvantation (AS01B or water for 
injection) (see Section 6.4 for a detailed description of the randomization method). 
• 
ThreeTwo-vaccination course given at 0, and 1 and 6 months. All vaccinations will 
be administered by the intramuscular route in the deltoid of the non-dominant arm. 
(Amended September 24, 2007) 
• 
Duration of the study: The intended duration per subject will be approximately 14 
months 
• 
7-day follow-up visits after each vaccination for the 12 first vaccinated subjects and 
30-day follow-up visits after each vaccination for all subjects. 
• 
Blood samples will be collected at 8 visits 
• 
Diary cards will be provided to the subjects to record temperature and local (at the 
injection site) or general adverse events occurring on the day of vaccination and 
during the 6 subsequent days (Day 0 to Day 6) (see Section 5.2.1.3) 
• 
One-month (Day 0 to Day 29) follow-up for unsolicited symptoms after each 
injection of the vaccine 
• 
Recording of serious adverse events (SAEs) in a prospective manner throughout the 
study period, i.e., the period beginning with the first vaccination and ending 6 11 
months after the third second vaccination. (Amended September 24, 2007) 
• 
Recording of SAEs related to study procedures during screening. 
• 
Three Two separate analyses will be performed on cleaned data: 
A first analysis will be performed when all data (immunogenicity and reactogenicity) 
up to and including 1 month post-vaccination II are available. 
A second analysis will be performed when all data (immunogenicity and 
reactogenicity) up to and including 1 month post-vaccination III are available. 
A third second analysis on the immunogenicity persistence data and SAEs data will 
be performed at the completion of the study (Month 12).(Amended September 24, 
2007) 
• 
Data collection: Remote Data Entry (RDE) 
• 
All details concerning the recruitment plan can be found in Appendix C. 
 
4. 
STUDY COHORT 
 
4.1. 
Number of subjects / centers 
 
This study will be conducted at a single center in Belgium. The target number of eligible 
subjects will be 180 (3 groups of 50 subjects and 3 groups of 10 subjects). 

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Refer to Section 10.3 for a description of the criteria used in the estimation of sample 
size. 
 
Please refer to Appendix C of this document for details of recruitment at the center. 
 
4.2. 
Inclusion criteria 
 
All subjects must satisfy the following criteria at study entry: 
 
• 
A male or female between and including 18--40 years at the time of first vaccination. 
• 
Written informed consent obtained from the subject prior to any study procedure. 
• 
Subjects who the investigator believes that they can and will comply with the 
requirements of the protocol (e.g., completion of the diary cards and return for 
follow-up visits). 
• 
Good general health without significant medical history, physical examination 
findings, or clinically significant abnormal laboratory results. 
• 
If the subject is female, she must be of non-childbearing potential, i.e. have a current 
tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of 
childbearing potential, she must practice adequate contraception for 30 days prior to 
vaccination, have a negative pregnancy test and continue such precautions for 2 
months after completion of the vaccination series. For a definition of adequate 
contraception, azoospermia and post-menopause please refer to the Glossary of 
Terms or to Section 5.5. 
• 
Negative for antibodies against HIV-1, HIV-2 and negative for HIV p24 antigen, 
using Abbott AxSYM autoanalyser within 56 days (8 weeks) prior to enrolment. 
Note: Subjects must be willing to accept HIV test results. Individuals who elect not 
to receive test results will not be enrolled. 
• 
Negative for anti-HBc Ab, HBsAg and anti-HCV Ab. 
 
4.3. 
Exclusion criteria for enrolment 
 
The following criteria should be checked at the time of study entry. If any apply, the 
subject must not be included in the study: 
 
• 
Women who are pregnant or breast-feeding. 
• 
Subjects with a history of, or current, alcohol or substance abuse. 
• 
The subject is at high risk of acquiring HIV according to the behavioural risk 
assessment questionnaire. 
• 
Morbid obesity 
• 
Previous inclusion in a HIV vaccines trial. 
• 
Receipt of live attenuated vaccines within 30 days of enrolment. 

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• 
Receipt of medically indicated subunit or killed vaccines (e.g., influenza, 
pneumococcal) or allergy treatment with antigen injections (including a tuberculin 
skin test) within 14 days of study vaccine administration. 
• 
Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccines within 30 days preceding the first dose of study vaccine, or planned 
use during the study period. 
• 
Prior receipt of HIV-1 vaccines or placebo in a previous HIV vaccine trial. 
• 
Receipt of blood products 120 days prior to HIV screening. 
• 
Receipt of immunoglobulin 120 days prior to HIV screening. 
• 
History of serious adverse reactions including anaphylaxis and related symptoms 
such as hives, respiratory difficulty, angioedema and abdominal pain to vaccines. 
• 
History of serious allergic reaction to any substance requiring hospitalization or 
emergency medical care (e.g., Steven-Johnson syndrome, bronchospasm, or 
hypotension). 
• 
History of immunodeficiency or autoimmune disease. 
• 
History of malignancy (unless there has been surgical excision followed by a 
sufficient observation period, of at least 5 years, to give a reasonable assurance of 
sustained cure and which, in the estimate of the investigator, is not likely to recur 
during the study period). 
• 
Chronic administration (defined as more than 14 days) of immunosuppressants or 
other immune-modifying drugs within six months prior to the first vaccination. (For 
corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled 
and topical steroids are allowed.) 
• 
History of type I or type II diabetes mellitus including cases controlled with diet 
alone. 
Note: A subject with past gestational diabetes is eligible. 
• 
Thyroid disease including history of thyroidectomy and diagnoses requiring 
medication. 
Note: A subject not requiring thyroid medicine within the past 12 months is eligible. 
• 
Acute disease at the time of enrolment. Acute disease is defined as the presence of a 
moderate or severe illness with or without fever. 
• 
Asthma requiring daily steroid or long acting agonist prevention. 
• 
Unstable asthma defined as: 
Sudden acute attacks occurring in less than three hours without an obvious trigger. 
Hospitalization for asthma in the last two years. 
• 
Food- or wine-induced asthma 
• 
Known sensitivity to sulfites or aspirin 

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• 
Bleeding disorder that was diagnosed by a physician; e.g., factor deficiency, 
coagulopathy or platelet disorder that requires special precautions. 
Note: A subject who states that he or she has easy bruising or bleeding, but does not 
carry a formal diagnosis and has intramuscular (IM) injections and blood draws 
without any adverse experience is eligible. 
• 
History of any serious neurologic disorder or seizure 
• 
History of major congenital defect 
• 
History of chronic fatigue syndrome or fibromyalgia 
• 
Splenectomy 
• 
Hypertension. 
Note: A subject with hypertension is eligible if he or she is controlled on medication 
and the documented blood pressure is less than 150/100. 
• 
Any medical, psychiatric or social condition, or occupational or other responsibility 
that, in the judgement of the investigator, would interfere with or serve as a 
contradiction to adherence to the study protocol or ability to give informed consent. 
 
4.4. 
Elimination criteria during the study 
 
The following criteria should be checked at each visit subsequent to the first visit. If any 
become applicable during the study, it will not require withdrawal of the subject from the 
study but may determine a subject's evaluability in the according-to-protocol (ATP) 
analysis. See Section 10.5 for definition of study cohorts to be evaluated. 
 
• 
Positive for antibodies against HIV-1, HIV-2 and positive for HIV p24 antigen, 
using Abbott AxSYM autoanalyser. 
• 
Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccines during the study period. 
• 
Chronic administration (defined as more than 14 days) of immunosuppressants or 
other immune-modifying drugs during the study period. For corticosteroids, this will 
mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are 
allowed. 
• 
Administration of a vaccine not foreseen by the study protocol during the period 
starting from 30 days (14 days in the case of subunit or killed vaccines [e.g., 
influenza, pneumococcal] or allergy treatment with antigen injections) before each 
administration of vaccine(s) and ending 30 days after. 
• 
Administration of immunoglobulins and/or any blood products during the study 
period. 
• 
Pregnancy 
• 
Intravenous drug use 
See Section 10.5 for definition of study cohorts to be evaluated. 

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4.5. 
Contraindications to subsequent vaccination 
 
The following adverse events (AEs) constitute absolute contraindications to further 
administration of GSK Biologicals' candidate vaccines; if any of these AEs occur during 
the study, the subject must not receive additional injections of vaccine but may continue 
other study procedures at the discretion of the investigator (see Section 9). The subject 
must be followed until resolution of the event, as with any AE (see Section 8.6): 
• 
Early or delayed onset reactions after vaccine administration such as anaphylaxis, 
bronchospasm, laryngeal oedema, generalized collapse, convulsions, encephalopathy 
or severe Arthus reaction. 
• 
Any event which is considered by the investigator and the sponsor to be serious or 
severe which would suggest any significant hazard that may be associated with the 
use of the study vaccine. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
including human immunodeficiency virus (HIV) infection. 
• 
Pregnancy (see Section 8.10). 
The following AEs constitute contraindications to administration of GSK Biologicals' 
candidate vaccines at that point in time; if any one of these AEs occurs at the time 
scheduled for vaccination, the subject may be vaccinated at a later date, within the time 
window specified in the protocol (see Section 5.4), or withdrawn at the discretion of the 
investigator (see Section 9). The subject must be followed until resolution of the event, as 
with any AE (see Section 8.5.3). 
• 
Acute disease at the time of vaccination. Acute disease is defined as the presence of a 
moderate or severe illness with or without fever. All vaccines can be administered to 
persons with a minor illness such as diarrhea, mild upper respiratory infection with 
or without low-grade febrile illness, i.e., oral temperature < 37.5°C/axillary 
temperature < 37.5°C. 
• 
Any vaccination less than 14 days (30 days in the case of live attenuated vaccines) 
before vaccine administration. 
• 
Oral temperature 37.5°C / axillary temperature 37.5°C. 
 
5. 
CONDUCT OF STUDY 
 
5.1. 
Ethics and regulatory considerations 
 
The study will be conducted according to Good Clinical Practice (GCP), the 1996 
Declaration of Helsinki (Appendix A) and local rules and regulations of the country. 
Submission of the protocol and any protocol amendments to regulatory agencies will 
occur in accordance with local regulatory requirements. For some countries, submission 
to the local regulatory authority may not be required. When submission to the local 
regulatory authority is required, the timing of the submission relative to IEC/IRB 
submission or approval and whether or not the authority will provide their approval of or 
favourable opinion on the protocol or amendment before it can be implemented will 
depend on local regulatory requirements. 

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5.1.1. 
Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) 
 
The IRB/IEC must be constituted according to the local laws/customs of each 
participating country. The ICH Harmonized Tripartite Guideline for Good Clinical 
Practice recommends that the IRB/IEC should include: 
 
a. 
At least five members. 
b. 
At least one member whose primary area of interest is in a non-scientific area. 
c. 
At least one member who is independent of the institution/ study site. 
Only those IRB/IEC members who are independent of the investigator and the sponsor of 
the study should provide opinion on a study-related matter. 
 
A list of IRB/IEC members and their qualifications should be obtained by the Central 
Study Coordinator (CSC) and the Principal Investigator. This protocol and any other 
documents that the IRB/IEC may need to fulfil its responsibilities, including subject 
recruitment procedures and information about payments and compensation available to 
subjects, will be submitted to the IRB/IEC by the Principal Investigator. Written and 
dated unconditional approval/favourable opinion from the IRB/IEC of the protocol and 
amendment (if any and applicable), written informed consent form, consent form updates 
(if any), subject recruitment procedure(s) (e.g. advertisements), and any other written 
information to be provided to subjects must be in the possession of the investigator and 
GSK before commencement of the study. This approval/favourable opinion must refer to 
the study by study title and number with exact protocol version and date, and should 
identify the documents reviewed and state the date of review. Relevant GSK Biologicals' 
data will be supplied by the Principal Investigator to the hospital/ university/ independent 
IRB/IEC for review and approval of the protocol. Verification of the unconditional 
approval/favourable opinion of the IRB/IEC will be transmitted by the Principal 
Investigator to the CSC prior to shipment of vaccine supplies and CRFs to the site. 
 
No deviations from, or changes to, the protocol should be initiated without prior written 
sponsor and IRB/IEC approval/ favourable opinion of an appropriate amendment, except 
when necessary to eliminate immediate hazards to the subjects or where permitted by all 
applicable regulatory requirements or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change of monitor[s], telephone number[s].) 
Administrative changes and amendments not submitted for approval are submitted to the 
IRB/IEC for information only. However, written verification that such documents were 
submitted should be obtained. Approvals/ verifications must be transmitted in writing to 
the CSC by the Principal Investigator. 
 
The IRB/IEC must be informed by the Principal Investigator of: 
 
• 
all subsequent protocol amendments, informed consent changes or revisions of other 
documents originally submitted for review, 
• 
serious and/or unexpected adverse events occurring during the study, where required, 

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• 
all subsequent protocol administrative changes (for information, except for US 
studies), 
• 
new information that may affect adversely the safety of the subjects or the conduct of 
the study, 
• 
an annual update and/or request for re-approval, where required, 
• 
when the study has been completed, where required. 
If a trial is prematurely terminated or suspended for reasons including, but not limited to, 
safety or ethical issues or severe non-compliance, the sponsor will promptly inform the 
regulatory authorities of the termination or suspension and the reason(s) for the 
termination or suspension. If required by applicable regulations, the investigator must 
inform the IEC/IRB promptly and provide the reason for the suspension or termination 
(see Appendix B for further details). 
 
5.1.2. 
Informed consent 
 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to GCP and to the ethical 
principles that have their origin in the 1996 Declaration of Helsinki. Prior to the 
beginning of the trial, the investigator should have the IRB/IEC's written 
approval/favourable opinion of the written informed consent form and any other written 
information to be provided to the subjects. 
 
Freely given informed consent should be obtained from every subject prior to clinical 
trial participation. 
 
Information should be given in both oral and written form whenever possible and as 
deemed appropriate by the IRB/IEC. 
 
An investigator or designate will describe the protocol to potential subjects face to face. 
The Informed Consent Form may be read to the subjects, but, in any event, the 
investigator or designate shall give the subjects ample opportunity to inquire about details 
of the study and ask any questions before dating and signing the Informed Consent Form. 
 
While informed consent information can be presented to groups at an initial information 
session, each subject must be given the opportunity to individually pose questions to the 
investigator or designate prior to the subject dating and signing the Informed Consent 
Form. 
 
Informed Consent Form must be in a language fully comprehensible to the prospective 
subjects. Informed consent shall be documented by the use of a written consent form 
approved by the IRB/IEC and signed and dated by the subjects and by the person who 
conducted the informed consent discussion. The signature confirms the consent is based 
on information that has been understood. All illiterate individuals will have the study, the 
Informed Consent Form explained to them point by point by the interviewer in the 
presence of an impartial witness. The witness will personally sign and date the consent 
form. Oral witnessed consent will replace written consent only in countries where the 

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local custom is contrary or if the subject's incapacity precludes this and provided that the 
local legal obligations are fulfilled. 
 
Each subject's signed informed consent form must be kept on file by the investigator for 
possible inspection by Regulatory Authorities and/or GSK Biologicals' professional and 
Regulatory Compliance persons. The subjects should receive a copy of the signed and 
dated written informed consent form and any other written information provided to the 
subjects, and should receive copies of any signed and dated consent form updates. Any 
amendments to the written information will be provided to subjects. 
 
Both the informed consent discussion and the written informed consent form and any 
other written information to be provided to the subjects should include explanations of 
the following: 
 
a. 
That the trial involves research. 
b. 
The purpose of the trial. 
c. 
The trial treatments and the probability for random assignment to each treatment. 
d. 
The trial procedures to be followed, including all invasive procedures. 
e. 
The subject's responsibilities. 
f. 
Those aspects of the trial that are experimental. 
g. 
The reasonably foreseeable risks or inconveniences to the subjects and, when 
applicable, to an embryo, fetus or nursing infant. 
h. 
The reasonable expected benefits. When there is no intended clinical benefit to 
subjects, the subjects should be made aware of this. 
i. 
The alternative procedure(s) or course(s) of treatment/ methods of prevention that 
may be available to subjects, and their important potential benefits and risks. 
j. 
The compensation and/or treatment available to subjects in the event of trial-related 
injury. 
k. 
The anticipated prorated payment, if any, to subjects for participating in the trial. 
l. 
The anticipated expenses, if any, to subjects for participating in the trial. 
m. That the subjects' participation in the trial is voluntary and subjects may refuse to 
participate or withdraw from the trial, at any time, without penalty or loss of benefits 
to which subjects are otherwise entitled. 
n. 
That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) 
will be granted direct access to the subject's original medical records for verification 
of clinical trial procedures and/or data, without violating the confidentiality of 
subjects, to the extent permitted by the applicable laws and regulations and that, by 
signing a written informed consent, the subject is authorizing such access. 
o. 
That records identifying subjects will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly 
available. If the results of the trial are published, subjects' identity will remain 
confidential. 

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p. 
That the subjects will be informed in a timely manner if information becomes 
available that may be relevant to the subjects' willingness for continued participation 
in the trial. 
q. 
The person(s) to contact for further information regarding the trial and the rights of 
trial subjects, and who to contact in the event of trial-related injury. 
r. 
The foreseeable circumstances and/or reasons under which a subject's participation 
in the trial may be terminated. 
s. 
The expected duration of a subject's participation in the trial. 
t. 
The approximate number of subjects involved in the trial. 
GSK Biologicals will prepare a model Informed Consent Form which will embody all the 
elements described above. While it is strongly recommended that this model document be 
followed as closely as possible, the informed consent requirements given in this document 
are not intended to pre-empt any local regulations which require additional information   
to be disclosed for informed consent to be legally effective. Clinical                  
judgement, local regulations and requirements should guide the final structure and 
content of the document. 
 
The investigator has the final responsibility for the final presentation of Informed 
Consent Form, respecting the mandatory requirements of local regulations. The consent 
form generated by the investigator with the assistance of the sponsor's representative, 
must be approved (along with the protocol, and any other necessary documentation) by 
the IRB/IEC and be acceptable to GSK Biologicals. 
 
5.2. 
General study aspects 
 
5.2.1. 
Study evaluations 
 
Assessment of the product will include a behavioural risk assessment questionnaire, 
clinical observations and monitoring of haematological, biochemical and immunologic 
parameters. 
 
5.2.1.1. 
Behavioural risk assessment questionnaire 
 
The behavioural risk assessment questionnaire is designed to determine the risk of 
infection based on sexual behaviour, sexually transmitted diseases (STD) and injection 
drug use. The questionnaire (hard copy) will be completed by the subjects in full 
confidentiality at screening and at visits 5 and 7. The subject's number will be used. The 
subject's classification (high risk or low risk) will be recorded in the electronic CRF 
(eCRF). 
 
At screening, high risk subjects will be excluded. During the study, subjects found at 
increased risk will not be eliminated but will receive accentuated HIV prevention 
counselling. 
 
The behavioural risk assessment questionnaire is attached. 

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5.2.1.2. 
Clinical observations 
 
Safety will be evaluated by monitoring of subjects in the clinic for 30 minutes after each 
vaccination. 
 
A 7-day follow-up (Day 0 to 6) of solicited local and general reactions will be performed 
by the subjects after each vaccination. Local reactions, e.g., pain, redness, swelling, and 
general reactions, e.g., temperature (fever), fatigue, headache, sweating, myalgia and GI 
symptoms, will be recorded by the subjects on diary cards. The intensity of solicited 
symptoms will be recorded. The relationship to vaccination of general solicited 
symptoms will be assessed by the investigator. All local solicited symptoms will be 
considered related to the vaccination. 
 
The occurrence, intensity and relationship to vaccination of unsolicited symptoms during 
a 30-day follow-up period (Day 0 to 29) after each vaccination and the occurrence and 
relationship of SAEs at any time during the whole study period will be recorded. 
 
5.2.1.3. 
Diary Cards 
 
To collect safety data about the vaccine, diary cards will be used for day-by-day 
recording of the solicited symptoms from Day 0 to Day 6 following each vaccination and 
collection of information on unsolicited symptoms and concomitant medication from 
Day 0 to Day 29 after each injection of the vaccine. Three kinds of diary cards will be 
used in this study (Table 2): 
 
• 
A first type of diary card will record information from Day 0 to Day 6 after each 
vaccination in the 12 first vaccinated subjects. 
• 
A second type of diary card will record information from Day 7 to Day 29 after each 
vaccination in the 12 first vaccinated subjects. 
• 
A third type of diary card will record information from Day 0 to Day 29 after each 
vaccination in all the other subjects. 
Subjects will be instructed to bring the completed diary card with them at the next visit 
and the investigator (or designee) will transcribe all information collected on the diary 
cards promptly in the eCRF as this information is needed for the scheduled safety 
evaluations. 

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Table 2 
Overview of diary cards 
 
Type of diary 
card 
Subjects 
Distribution 
Return 
Day 0 - Day 6 
12 first subjects of each dose group 
12 first subjects of each dose group 
12 first subjects of each dose group 
Visit 1 (Day 0) 
Visit 2 (Day 30) 
Visit 5 (Day 180) 
Follow-up Visit 1 (Day 7) 
Follow-up Visit 2 (Day 37) 
Follow-up Visit 5 (Day 187) 
Day 7 - Day 29 12 first subjects of each dose group 
12 first subjects of each dose group 
12 first subjects of each dose group 
Follow-up Visit 1 (Day 7) 
Follow-up Visit 2 (Day 37) 
Follow-up Visit 5 (Day 187) 
Visit 2 (Day 30) 
Visit 4 (Day 60) 
Visit 6 (Day 210) 
Day 0 - Day 29 48 other subjects of each dose group 
48 other subjects of each dose group 
48 other subjects of each dose group 
Visit 1 (Day 0) 
Visit 2 (Day 30) 
Visit 5 (Day 180) 
Visit 2 (Day 30) 
Visit 4 (Day 60) 
Visit 6 (Day 210) 
(Amended September 24, 2007) 
 
 
5.2.1.4. 
Laboratory parameters 
 
Effects on the haematological and biochemical parameters will be monitored at the 
Screening Visit, Visit 1 (Day 0), Visit 2 (Day 30), Visit 3 (Day 44), Visit 4 (Day 60), 
Visit 5 (Day 180), Visit 6 (Day 210 270) and Visit 7 (Day 360). (Amended September 
24, 2007) 
 
5.2.1.5. 
Immunogenicity parameters 
 
All subjects will be monitored longitudinally for HIV-specific serologic and cellular 
immune responses (refer to Section 5.4 flowsheet and Section 5.5 for details on 
immunogenicity determinations and timepoints). 
 
5.2.2. 
Detection of intercurrent HIV infection 
 
The study vaccine contains multiple antigens of the HIV-1 virus, therefore, vaccine- 
induced immune responses in study subjects detected by screening serologic assays 
potentially could be confused with natural infection. However, the risk for serological 
cross-reaction by 4th generation ELISAs including the Axysm test used in the study is 
extremely low. Nevertheless, several precautionary measures will be taken to clarify this 
distinction. 
 
• 
Frequent counselling on avoidance of HIV infection and pregnancy. 
The investigator or his delegate will ensure that the privacy and confidentiality of the 
subject is kept during these informative sessions. 
HIV Infection: subjects will receive information regarding HIV prevention and 
transmission. The following points will be explained to the subjects. 
 Knowledge: what is HIV, HIV modes of transmission, factors that increase 
the risk of becoming infected. 
 Risk reduction: never have unsafe/ unprotected sex (always use condoms and 
the correct use of condoms, provide condoms), have safer sex, have fewer or 

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less risky partners, avoid needle-sharing, avoidance of sex while high on 
drugs or alcohol. 
 HIV Testing: Why and when the subject should seek additional counselling 
and testing. Signs and symptoms of primary HIV infection (see below). 
 Vaccine: Remind the subjects that the effectiveness of these vaccines is not 
known. Therefore, it is very important that the subjects avoid any behaviour 
that would put them at risk for getting infected with HIV. 
 Answer any relevant questions from the subject. 
Additional counselling will be delivered for special situations: 
 Subjects with newly identified or suspected HIV infection 
 Subjects with a single, recent non-occupational HIV exposure 
 Subjects with a recent occupational exposure 
 Subjects with indeterminate HIV test results 
 Subjects seeking repeat HIV testing 
Pregnancy (female subjects only): notes on the following will be documented in the 
subject's file. 
 - The subject's contraceptive status will be assessed. 
 - The subject will be reminded of the importance of using contraception. 
• 
Signs and symptoms of HIV-1 infection: 
Signs or symptoms of acute HIV infection syndrome (e.g., sore throat, diarrhea, 
fever, chills, night sweats, neurologic syndromes and rash). 
and 
Signs and symptoms of an opportunisitic infection. 
• 
Laboratory assessment of potential intercurrent HIV-1 infection 
HIV Ag /Ab ELISA testing will be routinely performed at screening, vaccine dose 1, 
1 month post-vaccination III Month 9 and Month 12. (Amended September 24, 
2007) 
If intercurrent HIV-1 infection is suspected, further diagnostic work-up will be 
performed (see Appendix H). 
In addition to routine testing for HIV-1 infection planned during the course of the 
study, HIV tests may be requested by the investigator or the subject (free of charge) 
at any time during the study. 
The flowchart for the standard algorithm and the full procedure are presented in 
Appendix H of the protocol and will also be included in the study file. 
• 
Infected subjects will be withdrawn from the study and will be referred to the HIV 
referral unit at the University Hospital of Ghent for treatment and management of the 
HIV-1 infection. Neither the study sites, study investigators, nor GSK Biologicals 

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will be responsible for providing ongoing medical care or anti-retroviral medications 
in the event of HIV-1 infection. 
• 
At the final study visit (Visit 7, Month 12, Day 360) or following a subject's 
withdrawal from the study, a blood sample will be taken and stored. At the end of the 
study, these samples will be analysed using a panel of different HIV tests commonly 
used in Europe. 
 
5.3. 
Subject identification 
 
Subject numbers will be assigned sequentially to subjects consenting to participate in the 
study, according to the range of subject numbers allocated to the study center. 
 
5.4. 
Outline of study procedures 
 
The schedule of study procedures is summarized in Table 3. 

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Table 3 
List of study procedures 
 
Visit 
Screening 1 Follow- 
up visit 
11 
2 Follow- 
up visit 
21 
3 
4 
5 Follow- 
up visit 
51 
6 
7 
Timing (Months) 
Screening 0 
7 
1 
37 
44 
2 
6 
187 
7 9 
12 
Timing (Days) 
-56 to -1 
0 
30 
60 180 
210 360 
270 
Sampling time point 
PRE 
(M0) 
P l 
(M1) 
P ll 
(M1.5) 
P ll 
(M2) 
P ll 
(M6) 
P lll 
Pll 
(M7) 
(M9) 
P lll 
Pll 
(M12) 
Vaccination 
l 
ll 
lll 
Examination and 
Procedure: 
Signed Consent Form 
• 
Signed Addendum to 
Consent Form (Amended 
October 08, 2007) 
 •- 
• 
Randomization 
• 
Physical examination and 
vital signs 
• 
• 
• 
• 
• 
Demographic data 
• 
General medical history 
• 
Prevention Counselling 
(pregnancy and HIV) 
• 
• 
• 
• 
Inclusion/exclusion  criteria 
• 
○ 
Elimination criteria 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
Contraindications 
• 
• 
 •- 
Behavioural risk assessment 
[questionnaire to be filled in 
by the subject and high or 
low risk to be recorded on 
CRF] 
• 
• 
• 
Pre-vaccination body 
temperature 
• 
• 
 •- 
Distribution of diary card 
○ 
○1 
○ 
○1 
 ○- 
 ○ 1 
Return of diary card 
○1 
○ 
○1 
○ 
 ○ 1 
 ○- 
Transcription of solicited 
symptoms recorded by the 
subjects (Day 0 to Day 6) 
•1 
• 
•1 
• 
 •1 
 •- 
Recording of non-serious 
unsolicited adverse events 
occurring within one month 
post-vaccination by 
Investigator (Day 0 to Day 
29) 
•1 
• 
•1 
• 
 •1 
 •- 
Reporting of serious adverse 
events 
• 
• 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
• 
Record any concomitant 
medications 
• 
•1 
• 
•1 
• 
• 
•4 
 •1 
•4 
•4 
Study conclusion 
• 
 •- 
• 

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Visit 
Screening 1 Follow- 
up visit 
11 
2 Follow- 
up visit 
21 
3 
4 
5 Follow- 
up visit 
51 
6 
7 
Timing (Months) 
Screening 0 
7 
1 
37 
44 
2 
6 
187 
7 9 
12 
Timing (Days) 
-56 to -1 
0 
30 
60 180 
210 360 
270 
Sampling time point 
PRE 
(M0) 
P l 
(M1) 
P ll 
(M1.5) 
P ll 
(M2) 
P ll 
(M6) 
P lll 
Pll 
(M7) 
(M9) 
P lll 
Pll 
(M12) 
Vaccination 
l 
ll 
lll 
Blood Sample (ml): 
11 
101 
6.5 
96.5 96.5 56.5 
61 
11 
69 
Virology(4.5 ml) 
Hep B/C markers: anti HBC 
Ab, HBsAg, 
Anti HCV Ab 
• 
HIV Ag/Abt 
• 
• 
• 
• 
Panel of HlV tests (8 ml)* 
• 
Biochemistry/Haematology 
(6.5 ml) 
• 
• 
• 
• 
• 
• 
• 
• 
Serology (10 ml) 
Anti-p17,-24,-RT,-Nef,  -F4co 
antibodies (ELISA) 
• 
• 
• 
• 
 •- 
• 
Cellular-mediated 
immunity 
(40 or 80 ml)** 
p17-,24-,RT-,Nef-  Specific 
effector 
T-cells (ICS) 
• 
• 
• 
• 
 •- 
• 
Urine Sample: 
Pregnancy test (HCG), if 
applicable 
• 
• 
• 
 •- 
Note: The double-line border following Month 2 and Month 7 indicates the 2 overall interim analyses that will be 
performed on all serology and immunogenicity data obtained up to PII (M2) and PIII (M7). 
•: Is used to indicate a study procedure which requires documentation in the individual eCRF; O is used to indicate a 
study procedure that does not require documentation in the individual eCRF; •1: In the 12 first vaccinated subjects of 
each dose group only; •: Only those SAEs that are considered related to study procedures need to be recorded (see 
Section 8.4); •: To be recorded only if the subject is not a screening failure. •4 Recording of concomitant 
medications till 30 days after vaccination. Please refer to Section 6.9 for description of 
concomitant/contraindicated medication to be recorded. 
t Abbott AxSYM HIV Ag/Ab ELISA assay, which allows detection of Absto HIV-1 group "M" gp41, HIV-2 gp36 and HIV 
group "O" gp41, and detection of the HIV p24 Ag. 
* At the final study visit or following a subject's withdrawal from the study. 
** 80 mL of blood are needed for cellular-mediated immunity when cross-reactivity is determined pre-vaccination (Day 
0), PII (M 1.5) (Day 44) and PII (M2) (Day 60). Otherwise, 40 mL of blood are enough for classical cellular-mediated 
immunity assessment at the other time points. 
(Amended September 24, 2007) 
 
It is the investigator's responsibility to ensure that the intervals between visits are strictly 
followed (Table 4). 

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Table 4 
Intervals between study visits 
 
lnterval 
length of interval (Days) 
1 (Screening Visit 1) 
1 to 56 (8 weeks) 
2 (Visit 1 Follow-up Visit 1)* 
7- 8* 
3 (Visit 1 Visit 2) 
30 - 34 
4 (Visit 2 Follow-up Visit 2)* 
7 - 8* 
5 (Visit 2 Visit 3) 
14 2 
6 (Visit 2 Visit 4) 
30 - 34 
7 (Visit 1 Visit 5) 
180 14 
8 (Visit 5 Follow-up Visit 5)* 
7 - 8* 
9 (Visit 5 1Visit 6) 
30 - 34 270 21 
10 (Visit 5 Visit 7) 
180 14 
* For the 12 first vaccinated subjects only 
(Amended September 24, 2007) 
5.5. 
Detailed description of study stages/visits 
 
Evaluations and blood draws will be performed on all subjects at the timepoints indicated 
in the Flowsheet (Section 5.4), unless otherwise noted. 
 
When considering the enrollment of females of childbearing potential (see Section 4.2), 
please take note of the following definitions: 
 
• 
Adequate contraception is defined as a contraceptive method with failure rate of less 
than 1% per year when used consistently and correctly (when applicable, as 
mentioned in the product label) for example abstinence, combined or progestogen 
oral contraceptives, injectable progestogen, implants of levonorgestrel, oestrogenic 
vaginal ring, percutaneous contraceptive patches or intrauterine device (IUD) or 
intrauterine system (IUS), vasectomy with documented azoospermia of the sole male 
partner or double barrier method (condom or occlusive cap plus spermicidal agent). 
• 
For azoospermia, "documented" refers to the outcome of the investigator's or 
designee's medical examination of the subject or review of the subject's medical 
history for study eligibility, as obtained via a verbal interview with the subject or 
from the subject's medical records. 
• 
Post-menopause: Menopause is the age associated with complete cessation of 
menstrual cycles, menses, and implies the loss of reproductive potential by ovarian 
failure. A practical definition accepts menopause after one year without menses with 
an appropriate clinical profile at the appropriate age e.g. >45 years. 
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) will be collected and stored using exclusively those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 10.5 for definition of study 
cohorts to be evaluated). The investigator must ensure that his/her personnel and the 
laboratory(ies) under his/her supervision comply with this requirement. However, when 
GSK Biologicals does not provide material for collecting and storing clinical samples, 

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then appropriate materials from the investigator's site are to be used. Refer to Appendix 
D and Appendix E. 
 
The vaccinees will be observed closely for at least 30 minutes, with appropriate medical 
treatment readily available in case of a rare anaphylactic reaction following the 
administration of vaccines. 
 
The subjects will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious. 
 
5.5.1. 
Screening Visit (Day -56 to Day -1) 
 
• 
Signed informed consent form prior to initiation of subject screening. 
• 
Complete physical examination, including vital signs (supine blood pressure and 
heart rate). 
• 
Weight and height 
• 
Demographic data of the subjects: date of birth, gender and race. 
• 
Medical history and current medical status of the subjects. 
• 
Counselling on avoidance of HIV infection and pregnancy. 
The investigator or his/her delegate will ensure that the privacy and confidentiality of 
the subject is kept during these informative sessions. 
• 
Screening tests and evaluations will be used to determine the eligibility of each 
subject for the study. All inclusion and exclusion criteria must be assessed within 8 
weeks (56 days) prior to study entry. 
• 
Behavioural risk questionnaire (hard copy) to be filled in by the subject. 
• 
SAEs that are considered related to study participation or are related to GSK 
concomitant medication need to be recorded (see Section 8.4). 
• 
Collection of blood (11 mL) for virology, biochemistry and haematology. 
• 
HCG (Human Chorionic Gonadotropin) urine pregnancy test will be performed in 
female subjects of childbearing potential. 
• 
Screening failures will also be recorded in the eCRF (demography, eligibility criteria 
and study conclusion) (see Section 9.3). 
 
5.5.2. 
Study Visit 1: First vaccination (Day 0 - Month 0) 
 
Prior to Vaccination 
 
Note: All test results and assessments required for establishing eligibility must be 
completed. 
 
• 
Check inclusion and exclusion criteria 
• 
The subject will be randomized (Internet randomization will be used). 

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• 
History-directed physical examination and vital signs. 
• 
Pre-vaccination assessment of body temperature 
• 
Counselling on avoidance of HIV infection and pregnancy. 
• 
Check of contraindications to vaccination. 
• 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit (see Section 6.9). 
• 
Collection of blood (101 mL) for virology, biochemistry, haematology, serology and 
cellular-mediated immunity. 
• 
HCG (Human Chorionic Gonadotropin) urine pregnancy test will be performed in 
female subjects of childbearing potential. 
• 
Evaluations and blood draws must be performed prior to vaccination, but it is not 
necessary to have results (except for pregnancy test) prior to the administration of the 
vaccine. 
Vaccination 
 
• 
Randomization and vaccine number: upon providing the subject number, the 
randomization system will determine the treatment number to be used for the subject. 
• 
Vaccination: intramuscular administration in the deltoid muscle of the non-dominant 
arm. The vaccinees will be observed closely for at least 30 minutes, with appropriate 
medical treatment readily available in case of a rare anaphylactic reaction following 
the administration of vaccines. 
• 
Reporting of serious adverse events. The subjects will be instructed to contact the 
investigator immediately should they manifest any signs or symptoms they perceive 
as serious. 
• 
Diary cards will be provided for the subjects to record temperature and any local (at 
the injection site) or general adverse events occurring on the day of vaccination and 
the 6 following days. 
• 
The first 12 vaccinated subjects will be instructed to return their completed Day 0 to 
Day 6 diary cards on Day 7 to the investigator. All the other subjects will be 
instructed to return their Day 0 to Day 29 diary cards on Day 30 to the investigator. 
 
5.5.3. 
Follow-up Visit 1 (Day 7; for the 12 first vaccinated subjects only) 
 
• 
Check elimination criteria 
• 
The subjects will return their completed (Day 0 to Day 6) diary cards to the 
investigator, who will transcribe them into the eCRF. 
• 
Reporting of any unsolicited adverse events which might have occurred since 
vaccination. 
• 
Reporting of any serious adverse events which might have occurred since 
vaccination. 

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• 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit (see Section 6.9). 
• 
Subjects will be distributed Day 7 to Day 29 diary cards and will be instructed to 
return them completed on Day 30 to the investigator. 
 
5.5.4. 
Study Visit 2: Second vaccination (Day 30 - Month 1) 
 
Prior to Vaccination 
 
• 
The subjects will return their completed diary cards (Day 7 to Day 29 diary cards for 
the 12 first vaccinated subjects and Day 0 to Day 29 diary cards for all the other 
subjects) to the investigator, who will transcribe them into the eCRF. 
• 
The investigator will record any non-serious unsolicited adverse events which might 
have occurred within one month (Day 0 to Day 29) post-vaccination. 
• 
Reporting of serious adverse events which might have occurred since the last visit. 
• 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit (see Section 6.9). 
• 
History-directed physical examination and vital signs. 
• 
Pre-vaccination assessment of body temperature 
• 
Counselling on avoidance of HIV infection and pregnancy. 
• 
Check of elimination criteria. 
• 
Check of contraindications to vaccination. 
• 
A urine pregnancy test for females of reproductive potential will be performed. 
• 
Collection of blood (6.5 mL) for biochemistry and haematology. 
• 
Evaluations and blood draws must be performed prior to vaccination, but it is not 
necessary to have results (except for pregnancy test) prior to the administration of the 
vaccine. 
 
Vaccination 
• 
Vaccination: intramuscular administration in the deltoid muscle of the non-dominant 
arm. The vaccinees will be observed closely for at least 30 minutes, with appropriate 
medical treatment readily available in case of a rare anaphylactic reaction following 
the administration of vaccines. 
• 
Reporting of serious adverse events. The subjects will be instructed to contact the 
investigator immediately should they manifest any signs or symptoms they perceive 
as serious. 
• 
Diary cards will be provided for the subjects to record temperature and any local (at 
the injection site) or general adverse events occurring on the day of vaccination and 
the 6 following days. 

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• 
The first 12 vaccinated subjects will be instructed to return their completed Day 0 to 
Day 6 diary cards on Day 37 to the investigator. All the other subjects will be 
instructed to return their Day 0 to Day 29 diary cards on Day 60 to the investigator. 
 
5.5.5. 
Follow-up Visit 2 (Day 37; for the 12 first vaccinated subjects 
only) 
 
• 
Check elimination criteria 
• 
The subjects will return their completed (Day 0 to Day 6) diary cards to the 
investigator, who will transcribe them into the eCRF. 
• 
Reporting of any unsolicited adverse events which might have occurred since 
vaccination. 
• 
Reporting of any serious adverse events which might have occurred since 
vaccination. 
• 
Recording of any concomitant medication1treatment1vaccination taken since the last 
visit (see Section 6.9). 
• 
Subjects will be distributed Day 7 to Day 29 diary cards and will be instructed to 
return them completed on Day 60 to the investigator. 
 
5.5.6. 
Study Visit 3 (Day 44 - 2 weeks after second vaccination) 
 
• 
Check elimination criteria 
• 
Reporting of serious adverse events which might have occurred since the last visit. 
• 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit. 
• 
Collection of blood (96.5 mL) for biochemistry, haematology, serology and cellular- 
mediated immunity. 
 
5.5.7. 
Study Visit 4 (Day 60 - Month 2) 
 
• 
Check elimination criteria 
• 
The subjects will return their completed diary cards (Day 7 to Day 29 diary cards for 
the 12 first vaccinated subjects and Day 0 to Day 29 diary cards for all the other 
subjects) to the investigator, who will transcribe them into the eCRF. 
• 
The investigator will record any non-serious unsolicited adverse events which might 
have occurred within one month (Day 0 to Day 29) post-vaccination. 
• 
Reporting of serious adverse events which might have occurred since the last visit. 
• 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit (see Section 6.9). 
• 
Collection of blood (96.5 mL) for biochemistry, haematology, serology and cellular- 
mediated immunity. 

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• 
Study conclusion (for interim analysis). 
 
5.5.8. 
Study Visit 5: Third vaccination (Day 180 - Month 6) 
 
Prior to Vaccination 
 
• 
Signed  addendum to informed consent form prior to  study continuation. 
(Amended October 08, 2007) 
• 
History-directed physical examination and vital signs. 
 • 
Pre-vaccination assessment of body temperature 
• 
Counselling on avoidance of HIV infection and pregnancy. 
• 
Check of elimination criteria. 
• 
Check of contraindications to vaccination. 
• 
Behavioural risk assessment questionnaire (hard copy) to be filled in by the subject. 
• 
Reporting of any serious adverse events which might have occurred since 
vaccination. The subjects will be instructed to contact the investigator immediately 
should they manifest any signs or symptoms they perceive as serious. 
• 
Recordingofany contraindicated concomitantmedication/treatment/vaccination 
taken since the last visit (see Section 6.9). 
 • 
A urine pregnancy test for females of reproductive potential will be performed. 
• 
Collection of blood (56.5 mL) for biochemistry, haematology, serology and cellular- 
mediated immunity. 
• 
Evaluations and blood draws must be performed prior to vaccination, but it is not 
necessary to have results (except for pregnancy test) prior to the administration of the 
vaccine. 
Vaccination 
 
 • 
Vaccination: intramuscular administration in the deltoid muscle of the non-dominant 
arm. The vaccinees will be observed closely for at least 30 minutes, with appropriate 
medical treatment readily available in case of a rare anaphylactic reaction following 
the administration of vaccines. 
 • 
Reporting of serious adverse events. The subjects will be instructed to contact the 
investigator immediately should they manifest any signs or symptoms they perceive 
as serious. 
 •Diary cards will be provided for the subjects to record temperature and any local (at 
the injection site) or general adverse events occurring on the day of vaccination and 
the 6 following days. 
 • 
The first 12 vaccinated subjects will be instructed to return their completed Day 0 to 
Day 6 diary cards on Day 187 to the investigator. All the other subjects will be 
instructed to return their Day 0 to Day 29 diary cards on Day 210 to the investigator. 
(Amended September 24, 2007) 

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5.5.9. 
Follow-up Visit 5 (Day 187; in the first 12 vaccinated subjects 
only) 
 
 • 
Check elimination criteria 
 • 
The subjects will return their completed (Day 0 to Day 6) diary cards to the 
investigator, who will transcribe them into the eCRF. 
 • 
Reporting of any unsolicited adverse events which might have occurred since 
vaccination. 
 • 
Reporting of any serious adverse events which might have occurred since 
vaccination. 
 • 
Recording of any concomitant medication/treatment/vaccination taken since the last 
visit (see Section 6.9). 
 • 
Subjects will be distributed Day 7 to Day 29 diary cards and will be instructed to 
return them completed on Day 210 to the investigator. (Amended September 24, 
2007) 
 
5.5.10. 
Study Visit 6 (Day 210 270- Month 7 9) 
 
• 
Signedaddendum to informedconsent form prior to  study continuation. 
(Amended October 08, 2007) 
• 
Check elimination criteria 
 • 
The subjects will return their completed diary cards (Day 7 to Day 29 diary cards for 
the 12 first vaccinated subjects and Day 0 to Day 29 diary cards for all the other 
subjects) to the investigator, who will transcribe them into the eCRF. 
 • 
The investigator will record any non-serious unsolicited adverse events which might 
have occurred within one month (Day 0 to Day 29) post-vaccination. 
• 
Reporting of serious adverse events which might have occurred since the last visit. 
• 
Recordingofany contraindicated concomitantmedication/treatment/vaccination 
taken since the last visit (see Section 6.9). 
• 
Collection of blood (61 11 mL) for virology, biochemistry, and haematology, 
serology and cellular-mediated immunity. 
 • 
Study conclusion (for interim analysis). (Amended September 24, 2007) 
 
5.5.11. 
Study Visit 7 (Day 360 - Month 12) 
 
• 
Physical examination and vital signs 
• 
Behavioural risk assessment questionnaire (hard copy) to be filled in by the subject. 
• 
Reporting of any serious adverse events which might have occurred since the last 
visit 

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• 
Recording of any contraindicated concomitant medication/treatment taken since the 
last visit (see Section 6.9). 
• 
Collection of blood (69 mL) for virology, HIV tests panel, biochemistry, 
haematology, serology and cellular-mediated immunity. 
• 
Study conclusion (final analysis). 
 
5.6. 
Safety evaluation and processes for holding-on, stopping 
and/or restarting the trial 
 
5.6.1. 
Staggered design 
 
A staggered dose-escalation design will be used for safety reasons. 
 
A first group of 12 subjects (10 receiving the adjuvanted vaccine and 2 receiving the 
vaccine in WFI) will be enrolled to receive their first vaccination at the lowest dose (10 
g), at a rate of maximum 1 subject per day during the first 5 working days. Provided no 
safety issues leading to clinical hold or stop occurred (Figure 2), the 12 subjects will be 
allowed to receive their second vaccination on Day 30 according to the same rate 
(maximum 1 subject/day during the first 5 working days) and the remaining subjects of 
the same dose group (N=48) will receive their first vaccination. Then, a new group of 12 
subjects will be enrolled to receive their first vaccination at the medium dose (30 g) at 
the rate of maximum 1 subject per day during the first 5 working days. Provided no safety 
issues leading to clinical hold or stop occurred, subjects will be allowed to receive their 
second vaccination on Day 30 at the same rate and the remaining subjects (N=48) of the 
same dose group will receive their first vaccination. Then, a new group of 12 subjects will 
be enrolled to receive their first vaccination at the highest dose (90 g) at a rate of 
maximum 1 subject per day during the first 5 working days. Provided no safety issues 
leading to clinical hold or stop occurred, subjects will be allowed to receive their second 
vaccination on Day 30 at the same rate and the remaining subjects (N=48) of the same 
dose group will receive their first vaccination. Exactly the same methodological approach 
will be replicated for the third vaccination in each dose group(Amended September 24, 
2007) 
 
5.6.2. 
Review of safety data 
 
A safety review team (SRT), including as core members the GSK Biologicals' Central 
Safety Physician, the Clinical Development Manager and Biostatistician of the project, 
will be responsible for reviewing the safety data 'in-stream' (i.e. throughout the course of 
the study), as appropriate. In case a safety signal is observed or the predefined holding 
rules are met (see Section 5.6.3), the SRT leader is responsible for the urgent 
communication and escalation to the GSK Vaccine Safety Monitoring Board (VSMB), 
who will decide at an ad hoc meeting suspending or not the study. Whenever unblinding 
would be needed in the in-stream review of the safety data, an Internal Data Monitoring 
Committee (IDMC) will be constituted and designated by the Vice President - World 
Wide Regulatory, Epidemiology and Safety (VP-WWRES) and Vice President -World 
Wide Clinical Development (VP-WWCD), including three GSK Physicians from 

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Biologicals Clinical Safety and Pharmacovigilance (BCSP) and WW Clinical 
Development (WWCD) that are not otherwise involved in the conduct of the study, in 
order to ensure that the study related personnel will remain blinded to all investigational 
product treatment codes (if applicable) until the study has been completed per protocol 
or is terminated for any cause. 
 
Vaccinations are scheduled on Days 0, and 30 and 180 and additional safety evaluations 
7 days after each vaccination. The following events must occur within the specified 
timeframe to ensure proceeding to the next vaccination and to the next dose as per 
schedule. (Amended September 24, 2007) 
 
• 
The investigative site must complete eCRFs promptly. 
• 
The SRT must review the demographic and safety data for each subject within 2 
business days of receiving the listings/tables and, if warranted, instruct the site to 
withdraw individual subjects and/or suspend further vaccination at least 1 business 
day prior to the next vaccination. 
 
5.6.3. 
Holding rules 
 
Holding one or stopping rules are defined according to the following criteria: 
 
• 
At least 3 out of the 12 subjects develop a Grade 3 general solicited AE, during the 
7-day follow-up period after vaccination which persists at Grade 3 for more than 48 
hours and which is considered to be related to vaccination 
or 
 
• 
At least 4 out of the 12 subjects develop any other Grade 3 unsolicited AE 
considered to be related to vaccination during the 7-day follow-up period after 
vaccination 
or 
 
• 
At least 4 out of the 12 subjects develop any Grade 3 general solicited (persisting at 
Grade 3 for more than 48 hours and considered related to vaccination) or unsolicited 
AE (considered related to vaccination) during the 7-day follow-up period after 
vaccination 
or 
 
• 
At least one life threatening vaccine related SAE occurs. 
or 
 
• 
At least one subject shows ulceration (necrosis of the dermis) at the injection site 
following vaccination. 
These holding or stopping rules will be applied to each of the three vaccine doses (10, 30 
and 90 g) and to each of the three two vaccinations. (Amended September 24, 2007) 

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In addition to the above stated holding rules, the withdrawal of an individual subject from 
vaccination can be at the investigator's discretion for serious local and adverse events or 
for any serious laboratory adverse event considered to be associated with vaccination. 
For all such withdrawals, GSK Biological's CDM has to be informed promptly (see 
Section 9). 
 
5.6.4. 
Process for restarting vaccination/trial 
 
Although the vaccination may be put on hold temporarily, further vaccination will restart 
only if the VSMB agrees by consensus. In the absence of consensus, the issue will be 
brought back to VSMB for decision when further information has been obtained to 
address the concerns of individual members or will be escalated directly to the GSK 
Global Safety Board (GSB) for decision. 
 
5.6.5. 
Process for stopping of trial 
 
In the event that the trial is stopped, GSK Biologicals will inform both the IEC through 
the investigator and competent authorities. A report will be written detailing the rationale 
used for reaching the decision. 
 
5.7. 
Sample handling and analysis 
 
5.7.1. 
Treatment and storage of biological samples 
 
See Appendix D of the protocol for details of treatment and storage of biological samples. 
See Appendix E for instructions for shipment of biological samples. 
5.7.2. 
Laboratory assays 
 
The following measurements will be performed when indicated in the Flowsheet (Section 
5.4): 
 
5.7.2.1. 
Virology 
 
The following virology assessments will be performed in the Investigator's laboratory. 
 
• 
Abbott kits will be used for the analysis of: anti-HBc Ab (+1--): CORE Abbott 
AxSYM, HBsAg (+1--): HBsAg (V2) Abbott AxSYM and anti-HCV Ab (+1--): HCV 
version 3.0 Abbott AxSYM. 
• 
An Abbott kit will be used for the analysis of: 
HIV Ag/Ab ELISA test; Abbott AxSYM. 
If this test is positive, confirm using INNO-LIAImmunoblot Assay and proceed 
with algorithm to detect intercurrent HIV Infection as explained in Section 5.2.2 and 
Appendix H. 
• 
Panel of HIV tests commonly used in Europe 

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5.7.2.2. 
Biochemistry 
 
These tests will be performed in the Investigator's laboratory. 
 
• 
Sodium 
• 
Potassium 
• 
Urea 
• 
Creatinine 
• 
Alanine aminotransferase (ALT) 
• 
Aspartate aminotransferase (AST) 
 
5.7.2.3. 
Haematology 
 
These tests will be performed in the Investigator's laboratory. 
 
• 
Red blood cell count (RBC) 
• 
White blood cell count (WBC) 
• 
Differential count 
• 
Platelets count 
• 
Haemoglobin 
• 
Haematocrit 
 
5.7.2.4. 
Urinalysis 
 
• 
Human Chorionic Gonadotropin (HCG) will be determined using a urine pregnancy 
test in female subjects of childbearing potential. 
The GSK Biologicals' laboratory at Rixensart has established Quality Control Procedures 
and an established Quality System. Both are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department to 
document the competency of the facility to perform the required tests and support the 
reliability of the results. Methods and equipment are validated, where required. 
 
5.7.3. 
Immunological read-outs 
 
The following immunological read-outs (Table 5) will be performed when indicated in 
the Flowsheet (Section 5.4) and in Table 6: 

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Table 5 
Immunological read-outs (characteristics of the assays) 
 
Assay 
Assay 
method 
Test kit/ 
Manufacturer 
Assay unit 
Assay 
cut-off or 
limit of 
detection 
Laboratory 
Anti-p17,-24,-RT,- 
Nef, -F4co 
antibodies 
ELISA 
In-house 
ELISA 
EU/mL 
To be 
determined 
CEVAC, 
Belgium 
p17-,24-,RT-,Nef- 
specific effector 
T-cells 
Flow 
Cytometry, 
ICS 
In-house ICS 
Number of 
cytokine(s) 
positive cells 
per 106 cells 
To be 
determined 
*CEVAC, 
Belgium 
* Or GSK Biologicals, 
 
Table 6 
Immunological read-outs (timings, markers, numbers of subjects 
and laboratory) 
 
Blood sampling timepoint 
Marker 
No. 
subjects 
Laboratory 
Timing Timepoint Visit 
Pre 
Day 0 
1 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post II 
Day 44 
3 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post II 
Day 60 
4 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post II 
Day 180 
5 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post III 
Day 210 
6 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post III 
Day 360 
7 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
Post ll 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
* Or GSK Biologicals 
(Amended September 24, 2007) 
• 
Samples will not be labelled with information that directly identifies the subjects but 
will be coded with the identification number of the subject. 

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• 
Collected samples may be used for purposes related to the quality assurance of the 
laboratory tests described in this protocol. This may include the management of the 
quality of these current tests, the maintenance or improvement of these current tests, 
the development of new test methods for the markers described in this protocol, as 
well as making sure that new tests are comparable to previous methods and work 
reliably. 
• 
It may be that any findings in the present or in other studies necessitate further 
investigation by GSK Biologicals into the efficacy or immunogenicity of the 
vaccines and their constituents under study or further research in the disease under 
study. Under these circumstances, additional testing on the samples may be 
performed by GSK Biologicals outside the scope of this protocol. 
• 
A GSK Biologicals Research & Development Position Paper is available (upon 
request) which describes the rationale for and some examples of what these further 
investigations might include. 
• 
Any sample testing will be done in line with the consent of the individual subject. 
• 
Collected samples will be stored for up to 15 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines 
require different timeframes or different procedures, which will then be in line with 
the subject consent. These extra requirements need to be communicated formally to 
and discussed and agreed with GSK Biologicals. 
 
5.7.3.1. 
Serology: antibody responses 
 
Antibody level will be determined by evaluating antibody (IgG) responses to p17, p24, 
RT, Nef and F4co using standard ELISA techniques. The ELISA utilizes antibody and 
antigen interactions to test for the presence of specific antibodies in the serum sample. 
The antigens are chosen from the evaluated vaccine based on what is likely to be an 
immunogenic component. 
 
Partially purified antigen is pre-coated onto a 96-well plate. Serum samples are added to 
the plate followed by a secondary anti-human IgG antibody conjugated with an enzyme. 
The addition of substrate provides a means of detecting the serum antibody that is specific 
for the antigens. Positive control, calibrators are run on each plate in order to            
assess the relative titer of each test sample. Negative controls are also run on each plate to 
ensure specificity. 
 
5.7.3.2. 
Cell-mediated immune responses 
 
Flow cytometry, using Intracellular Cytokine Staining (ICS) provides information on the 
frequency of CD4+ and CD8+ T cells responding to the antigen. It provides 
simultaneously information on the frequency of CD4+ 1 CD8+ T-lymphocytes expressing 
molecules involved in immunity such as IFN-, IL-2, TNF-and/or CD40L. Other 
markers may be used for exploratory analysis and further definition of the quality of the 
induced immune response. 

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PBMCs are stimulated in vitro with pools of peptides covering the sequences of p17, p24, 
RT or Nef antigens for 2 hours; then intracellular block is added (to inhibit cytokine 
secretion) for an additional overnight incubation. The cells will be stained for surface 
markers (e.g. CD4+ or CD8+ for T cells), than fixed and permeabilized, and subsequently 
stained with fluorescent antibodies to detect cytokines. The cells will then be analysed by 
flow cytometry. 
 
6. 
INVESTIGATIONAL PRODUCT AND ADMINISTRATION 
 
6.1. 
Study vaccine 
 
The HIV candidate vaccine, F4co/AS01B, consists of two fractions to be used for 
reconstitution just prior to injection: 
 
• 
The freeze-dried fraction containing the F4co antigen, which is presented in a single- 
dose 3 mL clear glass vial. 
• 
The liquid fraction consisting of AS01B adjuvant system, which is presented in a 
single-dose 3 mL glass vial. 
• 
The HIV candidate vaccine contains 10, 30 or 90 g per dose of F4co recombinant 
protein as active ingredient, adjuvanted with AS01B adjuvant system. Three groups 
of 50 subjects will receive F4co antigen (10, 30 or 90 µg dose) reconstituted with the 
adjuvant AS01B and three groups of 10 subjects will receive F4co antigen (10, 30 or 
90 g dose) reconstituted with water for injection (WFI). The reconstitution of 
antigen and adjuvant or WFI occurs just prior to injection. 
• 
The vaccine contains sodium sulfite which can rarely cause severe allergic reactions. 
Please see the Investigator's Brochure for further details. 
F4co is a fusion protein that comprises 4 HIV-1 derived antigens arranged as follows: 
p24-RT-Nef-p17. Each of the four antigens entering into the F4co fusion protein are: 
 
• 
p24, a viral capsid protein coded by the gag gene 
• 
RT (reverse transcriptase), a viral enzyme responsible for transcribing the viral RNA 
into double-stranded DNA. This enzyme was mutated in one amino acid (Tryptophan 
229 substituted by Lysine) to remove the RT polymerase activity. This protein is 
coded by the pol gene 
• 
Nef, a regulatory protein coded by an open-reading-frame (ORF) that flanks the env 
gene 
• 
p17, a viral matrix protein coded by the gag gene. 
AS01B is a liposome-based adjuvant containing the immunostimulants 3-D-MPL and 
QS21. The monophosphoryl lipid A (3-D-MPL) molecule consists of a chemically 
detoxified form of the parent lipopolysaccharide (LPS) from the Gram negative 
bacterium Salmonella minnesota. The form used for the vaccine, 3-D-MPL(GSK 
Biologicals North America) is the 3-O-deacylated form of the monophosphoryl lipid A. 

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QS21 is a natural saponine molecule purified from the bark of the South American tree, 
Quillaja saponaria Molina. 
 
Water for injection (Ph. Eur. 0169) used for reconstitution of lyophilized F4co is 
produced by GSK Biologicals. Lots of WFI intended for clinical trials are commercial 
lots used for reconstitution of GSK Biologicals marketed vaccines. 
 
The candidate vaccine to be used has been developed and manufactured by GSK 
Biologicals. 
 
The Quality Control Standards and Requirements for the candidate vaccine are described 
in separate release protocols and the required approvals have been obtained. 
 
Table 7 
Composition of the study vaccines 
 
Vaccine 
Formulation (approximately per 
injection) 
Presentation 
Volume 
F4co (p24-RT-Nef-p17) 
10 g of p24-RT-Nef-p17 
20 mg sucrose 
630 g sodium sulfite 
Lyophilized 
pellet in vial 
N/A 
F4co (p24-RT-Nef-p17) 
30 g of p24-RT-Nef-p17 
20 mg sucrose 
630 g sodium sulfite 
Lyophilized 
pellet in vial 
N/A 
F4co (p24-RT-Nef-p17) 
90 g of p24-RT-Nef-p17 
20 mg sucrose 
630 g sodium sulfite 
Lyophilized 
pellet in vial 
N/A 
AS01B 
50 g of MPL® 
50 g QS21 
in a suspension of liposomes in 
phosphate buffered saline per 0.5 mL 
Liquid in 
monodose vial 
0.5 mL/dose 
Water for injection 
(WFI) 
Ph.Eur. 0169 
Liquid in 
single-dose 
syringe 
0.5 mL/dose 
Refer to the Investigator's Brochure for further information about the study product and 
its components. 
 
Details concerning vaccine supplies can be found in Appendix G. 
The following doses of antigens will be used: 
Treatment 
Dose 
(g) 
Adjuvant 
AS01B 
(Number of subjects) 
(
Water for injection 
(WFI) 
Number of subjects) 
F4co (p24-RT-Nef-p17) 
10 
50 
10 
F4co (p24-RT-Nef-p17) 
30 
50 
10 
F4co (p24-RT-Nef-p17) 
90 
50 
10 

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6.2. 
Dosage and administration 
 
6.2.1. 
Reconstitution of the F4co antigen with AS01B adjuvant 
 
Disinfect the top of the AS01B and F4co antigen vials with alcohol swabs and let dry. 
Aspirate the contents of the AS01B vial in a syringe and inject adjuvant into the vial of 
lyophilized antigen. Remove and discard the syringe and needle under appropriate safety 
precautions. Dissolve the pellet by gently shaking (by hands) the vial. Wait for 
approximately 1 minute to ensure complete dissolution of vial contents before 
withdrawing 0.5 mL of the reconstituted vaccine solution using a fresh needle and 
syringe. 
 
When reconstituted, the vaccine should not be kept for more than 4 hours at room 
temperature. 
 
6.2.2. 
Reconstitution of the F4co antigen with water for injection (WFI) 
 
Disinfect the top of the F4co antigen vial with alcohol swabs and let dry. Inject the 
complete contents of one pre-filled syringe of WFI into the vial of lyophilized antigen. 
Remove and discard the syringe and needle under appropriate safety precautions. 
Dissolve the pellet by gently shaking (by hands) the vial. Wait for approximately 1 
minute to ensure complete dissolution of vial contents before withdrawing 0.5 mL of the 
reconstituted vaccine solution using a fresh needle and syringe. 
 
When reconstituted, the vaccine should not be kept for more than 4 hours at room 
temperature. 
 
6.2.3. 
Administration of reconstituted vaccine 
 
Each 0.5 mL dose of the reconstituted vaccine can be injected after very gentle manual 
shaking and slight warm-up at room temperature. It cannot be kept for more than 4 hours 
at room temperature before being administered. 
 
The needles should be suitable for intramuscular administration. 
IMPORTANT: 
(1) The vaccine will be administered slowly intramuscularly in the deltoid muscle of the 
non-dominant arm by the physician or delegate, with drugs and material readily available 
to treat emergencies. 
(2) Any unused (not reconstituted) vaccine will be sent back to GSK Biologicals to be 
destroyed. 
 
The vaccinees will be observed closely for at least 30 minutes following the 
administration of vaccines, with appropriate medical treatment readily available in case 
of a rare anaphylactic reaction. 

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6.3. 
Storage 
 
All investigational products to be administered to subjects must be stored in a safe and 
locked place with no access by unauthorized personnel. 
 
Vaccines will be stored at the defined temperature range (i.e. +2 to +8°C1 36F to 46F). 
 
The storage temperature of vaccines will be monitored and recorded daily during working 
days, preferably at the same time of the day (e.g. at the beginning of the day). 
 
At a minimum, a calibrated thermometer will be placed close to the vaccines and will be 
used to monitor and record the daily temperature (actual, min and max temperatures will 
be logged). Additionally, a continuous temperature recording system (e.g. 90-day Cox 
Recorder) will be used as a back up device and it will be opened in case of any 
temperature deviation (temperature outside the defined range, i.e. +2 to +8°C/ 36F to 
46F) during weekends or holidays. Alternatively, the temperature monitoring system of 
the storage facility can be used (as a replacement of the GSK continuous temperature 
recording system), if: 
 
• 
proper functioning was demonstrated during the monitor's site evaluation, 
• 
if the system continues to work in case of a power failure, and 
• 
if the system is maintained regularly (e.g. once/year) as documented in the site files. 
It is also permitted to monitor the storage temperature using a validated temperature 
continuous recording device, provided it can read the daily actual and min/max 
temperatures, and that it keeps working after the alarm is activated. 
 
It is also required to place a validated freezing point indicator (e.g. Freeze Tag) close to 
the vaccines as a back-up device. 
 
Any temperature deviation, i.e. temperature outside the defined range (i.e. +2 to +8°C/ 
36F to 46F), must be reported within 24 hours to the sponsor's CSC. 
 
Following exposure to a temperature deviation, vaccines will not be used until written 
approval is given by the sponsor. 
 
Storage conditions for transport of vaccines from country medical department or dispatch 
center to study sites or between sites are described in Appendix G. 
 
6.4. 
Treatment allocation and randomization 
 
The target sample size is 180 subjects (50 subjects per adjuvanted groups and 10 subjects 
per non-adjuvanted groups). 

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6.4.1. 
Randomization of supplies 
 
Three randomization lists (one for each antigen dose: 10, 30 and 90 g) will be generated 
at GSK Biologicals, Rixensart, using a standard SAS(Statistical Analysis System) 
program and will be used to number the vaccines. A randomization blocking scheme 
(5:1) will be used to ensure that balance between treatments is maintained: a treatment 
number will identify uniquely the vaccine doses to be administered to the same subject. 
 
6.4.2. 
Randomization of subjects 
 
The treatment allocation at the investigator site will be performed using a central 
randomization system on Internet (SBIR). The randomization algorithm will use a 
minimization procedure accounting for centre and vaccine dose (10, 30 or 90 g). Center 
and dose minimization factors will have equal weight in the minimization algorithm. 
 
After having checked that a subject is eligible, and after informed consent has been 
obtained, the person in charge of the vaccination will access the randomization system on 
Internet to receive a treatment number. Upon providing a subject number and a vaccine 
dose (10, 30 or 90 g), the randomization system will use the minimization algorithm to 
determine the treatment number to be used for the subject. 
 
The actual treatment number used for the first vaccination of the subject must be recorded 
by the investigator in the eCRF (Rando/Treatment Allocation Section). 
 
When the first target number of 12 subjects has been reached for a given dose (10, 30 or 
90 g), the enrolment will be frozen for the safety evaluation. When a go decision has 
been taken, the enrolment will be re-opened for that dose until the total target number of 
60 subjects has been reached. 
 
The enrolment for each vaccine dose (adjuvanted or not) will be open in a staggered way. 
The enrolment for 30 g vaccine dose will be open after completion of enrolment for 10 
g vaccine dose and the enrolment for 90 g vaccine dose will be open after completion 
of enrolment for 30 g vaccine dose. 
 
6.5. 
Method of blinding and breaking the study blind 
 
The study will be blinded for the randomized allocation to the adjuvanted vaccine or to 
the vaccine without adjuvant but not for the dose (partially-blind design). Because of the 
differences between the adjuvanted and non-adjuvanted vaccines, the following steps will 
be taken to maintain the blinding: 
 
• 
The vaccine recipient and those responsible for the evaluation of safety and 
reactogenicity study parameters will all be unaware of which vaccine preparation 
was administered (observer-blind design). 
• 
The Principal Investigator and or the co-investigators will be responsible only for 
assessing safety and post-vaccination adverse events. 

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+32.2.656.80.09 or +32.2.656.51.16 
 
+32.477 404.713 
+32.474.53.48.68 
The immunological data, which will lead to the unblinding of the treatment groups, will 
not be available during the course of the trial to any investigator or any person involved 
in the clinical conduct of the study (including data cleaning). 
 
The investigator, or person designated by the investigator, should contact GSK 
Biologicals' Central Safety physician directly or via the local safety contact (see below 
and Study Contact for Emergency Code Break in Sponsor Information page) to discuss 
the need for emergency unblinding. No set of individual codes will be held at the GSK 
Biologicals' Central Safety Office. The GSK Biologicals' Central Safety Office will be 
allowed to access the individual randomization code. The code will be broken by the 
Central Safety physician (Study Contact for Emergency Code Break in Sponsor 
Information page) only in the case of medical events that the investigator1physician in 
charge of the subject feels cannot be treated without knowing the identity of the study 
vaccine(s). 
 
GSK Biologicals Clinical Safety Physician 
(Study contact for Emergency Code Break) 
Phone: 
Fax: PPD 
Mobile phone for 7/7 day availability: 
PPD 
Back-up mobile phone contact: 
PPD 
 
 
GSK Biologicals' policy (incorporating ICH E2A guidance, EU Clinical Trial Directive 
and Federal Regulations) is to unblind any SAE report associated with the use of the 
investigational product, which is unexpected and attributable/suspected, prior to 
regulatory reporting. The Central Safety physician is responsible for unblinding the 
treatment assignment in accordance with specified time frames for expedited reporting of 
SAEs (Refer to Section 8.8). 
 
The independent statistician who will perform the analysis will have access to the 
randomisation codes at the time of analysis and will be able to break the codes to perform 
it. 
 
6.6. 
Replacement of unusable vaccine 
 
Additional vaccines will be provided to replace those that are unusable (see Appendix G 
for details of supplies). 
 
In addition to the vaccines provided for the planned number of subjects (including over- 
randomization when applicable), at least 5% additional vaccines will be supplied. In case 
a vaccine is broken or unusable, the investigator should replace it with a replacement 
vaccine. Although the sponsor need not be notified immediately in these cases (except in 
the case of cold-chain failure), documentation of the use of the replacement vaccine must 
be recorded by the investigator on the vaccine administration page of the eCRF and on 
the vaccine accountability form. 
PPD

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The investigator will use the central randomization system (SBIR) to obtain the 
replacement vial number. The system will ensure, in a blinded manner, that the 
replacement vial is of the same formulation as the randomized vaccine. 
 
6.7. 
Packaging 
 
See Appendix G. 
 
6.8. 
Vaccine  accountability 
 
See Appendix G. 
 
6.9. 
Concomitant  medication/treatment 
 
At each study visit, the investigator should question the subject about any medication(s) 
taken. 
 
All concomitant medication, with the exception of vitamins and/or dietary supplements, 
administered at ANY time during the period starting with administration of each vaccine 
and ending 30 days after each injection of study vaccine are to be recorded with generic 
name of the medication (trade names are allowed for combination drugs, i.e. multi- 
component drugs), medical indication, total daily dose, route of administration, start and 
end dates of treatment. 
 
Any treatments and/or medications specifically contraindicated, e.g., any 
immunoglobulins, other blood products and any immune modifying drugs administered 
within 4 months before the study or at any time during the study period are to be recorded 
with generic name of the medication (trade names are allowed for combination drugs 
only), medical indication, total daily dose, route of administration, start and end dates of 
treatment (see Sections 4.3 and 4.4). 
 
Any vaccine not foreseen in the study protocol administered in the period beginning 30 
days (14 days in the case of subunit or killed vaccines [e.g., influenza, pneumococcal] or 
allergy treatment with antigen injections) preceding each injection of study vaccine and 
ending 30 days after each injection of study vaccine is to be recorded with trade name, 
route of administration and date(s) of administration (see Sections 4.3 and 4.4). 
 
A prophylactic medication is a medication administered in the absence of ANY symptom 
and in anticipation of a reaction to the vaccination (e.g. an anti-pyretic is considered to be 
prophylactic when it is given in the absence of fever [oral / axillary temperature < 
37.5°C] and any other symptom, to prevent fever from occurring). Any concomitant 
medication administered prophylactically in anticipation of reaction to the vaccination 
must be recorded in the eCRF with generic name of the medication (trade names are 
allowed for combination drugs only), total daily dose, route of administration, start and 
end dates of treatment and coded as 'Prophylactic'. 
 
Concomitant medication administered for the treatment of an AE or SAE within the 
follow-up period for adverse events must be recorded in the eCRF with generic name of 

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the medication (trade names are allowed for combination drugs only), medical indication 
(including which AE/SAE), total daily dose, route of administration, start and end dates 
of treatment. Similarly, concomitant medication administered for the treatment of an 
SAE, at any time, must be recorded on the SAE Report Form. Refer to Section 8.2 for 
definition of SAE. 
 
7. 
HEALTH ECONOMICS 
 
7.1. 
Outcomes measurement and analysis 
 
Not applicable 
 
7.2. 
Economic data collection and analyses 
 
Not applicable 
 
8. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
The investigator is responsible for the detection and documentation of events meeting the 
criteria and definition of an adverse event (AE) or serious adverse event (SAE) as 
provided in this protocol. During the study, when there is a safety evaluation, the 
investigator or site staff will be responsible for detecting AEs and SAEs, as detailed in 
this section of the protocol. 
 
Each subject will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious. 
 
8.1. 
Definition of an adverse event 
 
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 
 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally 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. 
 
Examples of an AE include: 
 
• 
New conditions detected or diagnosed after investigational product 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 
investigational product or a concurrent medication (overdose per se should not be 
reported as an AE/SAE). 

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• 
Signs, symptoms temporally associated with vaccine administration. 
Examples of an AE DO NOT 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. 
AEs may include pre- or post-treatment events that occur as a result of protocol-mandated 
procedures (i.e. invasive procedures, modification of subject's previous therapeutic 
regimen). 
 
N.B. AEs to be recorded as endpoints (solicited events) are described in Section 8.4.1. All 
other AEs will be recorded as UNSOLICITED AES. 
 
Example of events to be recorded in the medical history section of the eCRF: 
 
• 
Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
start of the study (i.e. prior to the first study vaccination). 
 
8.2. 
Definition of a serious adverse event 
 
A SAE is any untoward medical occurrence that: 
 
a. 
results in death, 
b. 
is life-threatening, 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
 
c. 
requires hospitalization or prolongation of existing hospitalization, 
NOTE: In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician's office or out- 
patient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfils any other serious criteria, the event is 
serious. When in doubt as to whether "hospitalization" occurred or was necessary, the 
AE should be considered serious. 
 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
 
d. 
results in disability/incapacity, or 

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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, 
diarrhoea, influenza, and accidental trauma (e.g. sprained ankle) which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption. 
 
e. 
is a congenital anomaly/birth defect in the offspring of a study subject. 
f. 
Medical or scientific judgement 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. 
 
8.3. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events and serious 
adverse events 
 
Abnormal laboratory findings (e.g., clinical chemistry, haematology, urinalysis) or other 
abnormal assessments (e.g., vital signs) that are judged by the investigator to be clinically 
significant will be recorded as AEs or SAEs if they meet the definition of an AE, as 
defined in Section 8.1 or SAE, as defined in Section 8.2. Clinically significant abnormal 
laboratory findings or other abnormal assessments that are detected during the study or 
are present at baseline and significantly worsen following the start of the study will be 
reported as AEs or SAEs. 
 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
 
8.4. 
Time period, frequency, and method of detecting adverse 
events and serious adverse events 
 
All AEs occurring within 30 days following administration of each vaccine must be 
recorded on the AE form in the subject's eCRF, irrespective of intensity or whether or not 
they are considered vaccination-related. 
 
The standard time period for collecting and recording SAEs will begin at the first receipt 
of vaccine and will end 6 11 months following injection of the last dose of vaccine for 
each subject. See Section 8.7 for instructions for reporting and recording SAEs. 
(Amended September 24, 2007) 
 
Additionally, in order to fulfil international reporting obligations, SAEs that are related to 
study participation (e.g. procedures, invasive tests, a change from existing therapy) or are 
related to a GSK concurrent medication will be collected and recorded from the time the 
subject consents to participate in the study until she/he is discharged. 

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The investigator will inquire about the occurrence of AEs/SAEs at every visit/contact 
during the study. 
 
All AEs either observed by the investigator or one of his clinical collaborators or reported 
by the subject spontaneously or in response to a direct question will be evaluated by the 
investigator. AEs not previously documented in the study will be recorded in the AE form 
within the subject's eCRF. The nature of each event, date and time (where appropriate) of 
onset, outcome, intensity and relationship to vaccination should be established. Details of 
any corrective treatment should be recorded on the appropriate page of the eCRF. Refer 
to Section 6.9. 
 
As a consistent method of soliciting AEs, the subject should be asked a non-leading 
question such as: 
 
"Have you felt different in any way since receiving the vaccine or since the previous 
visit?" 
 
N.B. 
The investigator should record only those AEs having occurred within the time 
frame defined above. 
 
AEs already documented in the eCRF, i.e. at a previous assessment, and designated as 
"not recovered/not resolved" or "recovering/resolving" should be reviewed at subsequent 
visits, as necessary. If these have resolved, the documentation in the eCRF should be 
completed. 
 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator or designate will record all relevant information regarding 
an AE on the Adverse Event screen within the subject's eCRF. The investigator or 
designate will also record all relevant information regarding the SAE on the SAE screens 
in the eCRF. 
 
The electronic system using SAE screens in the eCRF will be the primary mode for 
reporting SAEs to GSK Biologicals during the study period. In case this electronic 
system for reporting SAEs does not work or after clinical database freezing, paper SAE 
Report Forms and the facsimile (Fax) system should be used to report SAEs. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms. 
 
8.4.1. 
Solicited adverse events 
 
Solicited symptoms are the symptoms that are most likely to occur. A 7-day follow-up 
(Day 0 to 6) of solicited adverse events will be performed by the subjects after each 
vaccination. Data concerning the following adverse events will be solicited using diary 
cards provided by the sponsor. 

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Solicited local (injection site) AEs 
 
Table 8 
Solicited local adverse events 
 
 
 
Solicited general AEs 
 
Table 9 
Solicited general adverse events 
 
 
 
 
N.B. 
Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be 
recorded. 
Fever 
Fatigue 
Headache 
Sweating 
Myalgia 
Gastro-intestinal symptoms (nausea, vomiting, diarrhea 
and/or abdominal pain) 
Pain at injection site 
Redness at injection site 
Swelling at injection site 

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8.5. 
Evaluating adverse events and serious adverse events 
 
8.5.1. 
Assessment of intensity 
 
Intensity of the following AEs will be assessed as described: 
 
Table 10 
Intensity scales for solicited symptoms 
 
Adverse Event 
lntensity grade 
Parameter 
Pain at injection site 
0 
Absent 
1 
Painful on touch 
2 
Painful when limb is moved 
3 
Pain that prevents normal activity 
Redness at injection site 
Record greatest surface diameter in mm 
Swelling at injection site 
Record greatest surface diameter in mm 
Fever* 
Record temperature in °C 
Headache 
0 
Normal 
1 
Headache that is easily tolerated 
2 
Headache that interferes with normal activity 
3 
Headache that prevents normal activity 
Fatigue 
0 
Normal 
1 
Fatigue that is easily tolerated 
2 
Fatigue that interferes with normal activity 
3 
Fatigue that prevents normal activity 
Sweating 
0 
Normal 
1 
Sweating that is easily tolerated 
2 
Sweating that interferes with normal activity 
3 
Sweating that prevents normal activity 
Myalgia 
0 
None 
1 
Myalgia that is easily tolerated 
2 
Myalgia that interferes with normal activity 
3 
Myalgia that prevents normal activity 
Gastrointestinal  symptoms 
(nausea, vomiting, diarrhoea and/or 
abdominal pain) 
0 
Gastrointestinal symptoms normal 
1 
Gastrointestinal symptoms that are easily tolerated 
2 
Gastrointestinal symptoms that interfere with normal 
activity 
3 
Gastrointestinal symptoms that prevent normal 
activity 
*Fever is defined as axillary or oral temperature 37.5°C. 
 
The maximum intensity of local injection site redness/swelling will be scored at GSK 
Biologicals as follows: 
 
0 
: 
0 mm 
1 
: 
> 0 to 20 mm 
2 
: 
> 20 to 50 mm 
3 
: 
> 50 mm 
 
 

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The investigator will make an assessment of the maximum intensity that occurred over 
the duration of the event for all other AEs, i.e. unsolicited symptoms, including SAEs 
reported during the study. The assessment will be based on the investigator's clinical 
judgement. The intensity of each AE and SAE recorded in the Adverse Event screen 
within the subject's eCRF, SAE screens in the eCRF or SAE Report Form (if back-up 
reporting system is used) should be assigned to one of the following categories: 
 
1 (mild) 
= 
An AE which is easily tolerated by the subject, causing 
minimal discomfort and not interfering with everyday 
activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities. Such an 
AE would, for example, prevent attendance at work and 
would necessitate the administration of corrective therapy. 
 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. 
Grade 3 is a category utilized for rating the intensity of an event; and both AEs 
and SAEs can be assessed as Grade 3. An event is defined as 'serious' when it 
meets one of the pre-defined outcomes as described in Section 8.2. 
 
8.5.2. 
Assessment of causality 
 
The investigator is obligated to assess the relationship between investigational product 
and the occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. Alternative causes, such as natural history of the underlying 
diseases, concomitant therapy, other risk factors and the temporal relationship of the 
event to the investigational product will be considered and investigated. The investigator 
will also consult the Investigator's Brochure in the determination of his/her assessment. 
 
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However, it is very 
important that the investigator always makes an assessment of causality for every event 
prior to completion and data submission of the SAE screens in eCRF (or transmission of 
the SAE Report Form to GSK Biologicals if back-up reporting is used). The investigator 
may change his/her opinion of causality in light of follow-up information, amending the 
SAE screens in eCRF (or SAE Report Form if back-up reporting system is used). The 
causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
In case of concomitant administration of multiple vaccines, it may not be possible to 
determine the causal relationship of general AEs to the individual vaccines administered. 
The investigator should, therefore, assess whether the AE could be causally related to 
vaccination rather than to the individual vaccines. 

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All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question: 
 
Is there a reasonable possibility that the AE may have been caused by the investigational 
product ? 
 
NO 
: 
The AE is not causally related to administration of the study 
vaccine(s). There are other, more likely causes and administration 
of the study vaccine(s) is not suspected to have contributed to the 
AE. 
YES 
: 
There is a reasonable possibility that the vaccine(s) contributed to 
the AE. 
Non-serious and serious AEs will be evaluated as two distinct events. If an event meets 
the criteria to be determined "serious" (see Section 8.2 for definition of SAE), it will be 
examined by the investigator to the extent to be able to determine ALL contributing 
factors applicable to each SAE. 
 
Other possible contributors include: 
 
• 
Medical history 
• 
Other medication 
• 
Protocol required procedure 
• 
Other procedure not required by the protocol 
• 
Lack of efficacy of the vaccine(s), if applicable 
• 
Erroneous administration 
• 
Other cause (specify). 
 
8.5.3. 
Medically attended visits 
 
For each solicited and unsolicited symptom the subject experiences, the subject will be 
asked if they received medical attention defined as hospitalization, an emergency room 
visit or a visit to or from medical personnel (medical doctor) for any reason and this 
information will be recorded in the eCRF. 
 
8.6. 
Follow-up of adverse events and serious adverse events 
and assessment of outcome 
 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide further information to GSK Biologicals on the subject's condition. 
 
All AEs and SAEs documented at a previous visit/contact and designated as not 
recovered/not resolved or recovering/resolving will be reviewed at subsequent 
visits/contacts. 

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Investigators will follow-up subjects: 
 
• 
with SAEs or subjects withdrawn from the study as a result of an AE, until the event 
has resolved, subsided, stabilized, disappeared, the event is otherwise explained, or 
the subject is lost to follow-up; 
• 
or, in the case of other non-serious AEs, until they complete the study or they are lost 
to follow-up. 
Clinically significant laboratory abnormalities will be followed up until they have 
returned to normal, or a satisfactory explanation has been provided. Additional 
information (including but not limited to laboratory results) relative to the subsequent 
course of such an abnormality noted for any subject must be made available to the Study 
Monitor. 
 
GSK Biologicals may request that the investigator perform or arrange for the conduct of 
supplemental measurements and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognized follow-up period, GSK 
Biologicals will be provided with a copy of any available post-mortem findings, 
including histopathology. 
 
New or updated information will be recorded on the originally completed SAE screens in 
eCRF. The update and submission of SAE screens in eCRF should be done within 24 
hours of receipt of the follow-up information as outlined in Section 8.7.1. 
 
When paper SAE Report Form is used as back-up system during the study period, if 
electronic SAE reporting system does not work, the investigator or designate should 
update the SAE screens in eCRF once the electronic system is working again before 
using it to report additional information. 
 
When paper SAE Report Form is used as back-up system (after clinical database 
freezing), new or updated information is to be recorded on the originally completed SAE 
Report Form, with all changes signed and dated by the investigator. The updated SAE 
Report Form should be resent to GSK Biologicals within 24 hours of receipt of the 
follow-up information as outlined in Section 8.7.1. In case paper SAE Report Forms are 
used, it is not acceptable for the investigator to send photocopies of the subject's medical 
records to GSK Biologicals in lieu of the appropriate completed AE/SAE pages. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK Biologicals. In this instance, all subject identifiers will be blinded on 
the copies of the medical records prior to submission to GSK Biologicals. 
 
Outcome of any non-serious AE occurring within 30 days post-vaccination (i.e. 
unsolicited AE) or any SAE reported during the entire study will be assessed as: 
 
• 
Recovered/resolved 
• 
Notrecovered/notresolved 
• 
Recovering/resolving 

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• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
 
8.7. 
Prompt reporting of serious adverse events to GSK 
Biologicals 
 
The electronic system using SAE screens in the eCRF will be the primary mode for 
reporting SAEs to GSK Biologicals during the study period. In case this electronic 
system for reporting SAEs does not work or after clinical database freezing, paper SAE 
Report Forms and the facsimile (Fax) system should be used to report SAEs. 
 
8.7.1. 
Time frames for submitting serious adverse event reports to GSK 
Biologicals 
 
SAEs will be reported promptly to GSK once the investigator determines that the event 
meets the protocol definition of an SAE. 
 
The investigator or designate will encode and submit relevant information on the SAEs in 
the SAE screens in eCRF WITHIN 24 HOURS OF HIS/HER BECOMING AWARE OF THESE 
EVENTS. Additional or follow-up information relating to the initial SAE report is also to 
be encoded and submitted in the SAE screens in eCRF within 24 hours of receipt of such 
information. 
 
When paper SAE Report Form is used as back-up system (if electronic SAE reporting 
system does not work or after clinical database freezing), the investigator or designate 
will fax the SAE reports to GSK Biologicals'Central Safety for Serious Adverse Event 
Reporting. Additional or follow-up information relating to the initial SAE report is also to 
be reported to the GSK Biologicals'Central Safety for Serious Adverse Event Reporting 
within 24 hours of receipt of such information. 
 
8.7.2. 
Completion and transmission of serious adverse event reports to 
GSK Biologicals 
 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator or designate will encode and submit the information in the SAE screens in 
eCRF within 24 hours as outlined in Section 8.7.1. The SAE screens in eCRF will always 
be completed as thoroughly as possible with all available details of the event and 
submitted by the investigator or designate. If the investigator or designate does not have 
all information regarding an SAE, he1she will not wait to receive additional information 
before notifying GSK of the event and completing the SAE screens in eCRF. The SAE 
screens in eCRF should be updated when additional information is received WITHIN 24 
HOURS as outlined in Section 8.7.1. 
 
When paper SAE Report Form is used as back-up system (if electronic SAE reporting 
system does not work or after clinical database freezing), the investigator or designate 
will report relevant information on SAEs to GSK Biologicals within the 24 hours as 
outlined in Section 8.7.1. The SAE Report Form will always be completed as thoroughly 

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, 
+32.2.656.79.24 
+32.2.656. 80.44 
 
+32 2 656 8850 
+32 2 656 51 16 or +32 2 656 80 09 
+32 477 404 713 
as possible with all available details of the event, signed by the investigator or designate, 
and forwarded to GSK Biologicals within the designated time frames. If the investigator 
or designate does not have all information regarding a SAE, he/she will not wait to 
receive additional information before notifying GSK Biologicals of the event and 
completing the form. When additional information is received on a SAE reported to GSK 
Biologicals using the back-up paper SAE Report Form during the study period, the 
electronic system should be used to report the additional information within 24 hours if 
the electronic system is working again and only after updating the SAE screens in eCRF 
once the electronic system was working again. When additional information is received 
on a SAE after clinical database freezing, the paper SAE Report Form should be updated 
and forwarded to GSK Biologicals within 24 hours as outlined in Section 8.7.1. 
 
The investigator will always provide an assessment of causality at the time of the initial 
report as described in Section 8.5.2. 
 
In rare circumstances, if the electronic system for reporting SAEs does not work and in 
the absence of facsimile equipment, notification by telephone is acceptable, with a copy 
of the SAE Report Form sent by email or by mail. Initial notification via the telephone 
does not replace the need for the investigator or designate to complete and submit SAE 
screens in the eCRF (or complete and sign the SAE Report Form if back-up system need 
to be used) as outlined in Section 8.7.1. 
 
In the event of a death determined by the investigator to be related to vaccination, 
completion of SAE screens in the eCRF 1 sending of the fax (if electronic SAE reporting 
system does not work or after clinical database freezing) must be accompanied by 
telephone call to the Study Contact for Reporting SAEs. 
 
Study Contact for Reporting SAEs 
  
Central Study Coordinator, Clinical R & D 
GlaxoSmithKline Biologicals 
Tel: PPD 
Fax: PPD 
E-mail address:  
Back-up Study Contact for Reporting SAEs 
GSK Biologicals Clinical Safety Physician 
Tel: PPD 
Fax: PPD 
Mobile phones for 717 day availability: 
PPD 
Back-up mobile phone contact: 
 
24/24 hour and 7/7 day availability 
(Amended September 24, 2007) 
PPD
PPD
PPD

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8.8. 
Regulatory reporting requirements for serious adverse 
events 
 
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.7. GSK Biologicals has a legal responsibility to promptly notify, as 
appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met. 
 
The investigator, or responsible person according to local requirements, will comply with 
the applicable local regulatory requirements related to the reporting of SAEs to the 
IRB/IEC and, if required, to the applicable government authority. 
 
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to investigational product and unexpected. The purpose 
of the report is to fulfil specific regulatory and Good Clinical Practice (GCP) 
requirements, regarding the product under investigation. 
 
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 Biologicals will 
file it with the Investigator's Brochure or other appropriate study documentation and will 
notify the IRB or IEC, if appropriate according to local requirements. 
 
8.9. 
Post-study adverse events and serious adverse events 
 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
detection period defined in Section 8.4. Investigators are not obligated to actively seek 
AEs or SAEs in former study participants. 
 
However, if the investigator learns of any SAE, including a death, at any time after a 
subject has been discharged from the study, and he/she considers the event reasonably 
related to the investigational product, the investigator will promptly notify the Study 
Contact for Reporting SAEs. 
 
After clinical database freezing, if SAE follow-ups or new SAEs have to be reported, the 
investigator or designate should use paper SAE Report Forms and the facsimile (Fax) 
system. 
 
8.10. 
Pregnancy 
 
Subjects who become pregnant during the study (up to maximum 30 days after receiving 
the last vaccine injection) must not receive additional injections of study vaccine but may 
continue other study procedures at the discretion of the investigator. 
 
The investigator, or his/her designee, will collect pregnancy information on any subject 
who becomes pregnant while participating in this study. The investigator, or his/her 

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designee, will record pregnancy information on the Pregnancy Report Form and submit it 
to GSK within 24 hours of learning of a subject's pregnancy. The subject will be followed 
to determine the outcome of the pregnancy. At the end of the pregnancy, whether that be 
full-term or prematurely, information on the status of the mother and child will be 
forwarded to GSK. Generally, follow-up will be no longer than six to eight weeks 
following the estimated delivery date. 
 
While pregnancy itself is not considered an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or a 
SAE, as described in Section 8.1 and 8.2, and will be followed as described in Section 
8.5.3. 
 
A spontaneous abortion is always considered to be a SAE and will be reported as 
described in Section 8.7. Furthermore, any SAE occurring as a result of a post-study 
pregnancy AND considered reasonably related in time to receipt of the investigational 
product by the investigator, will be reported to GSK Biologicals as described in Section 
8.9. While the investigator is not obligated to actively seek this information from former 
study participants, he/she may learn of a pregnancy through spontaneous reporting. 
 
Information on pregnancies identified during the screening phase/prior to vaccine 
administration does not need to be collected; this information need not be communicated 
to safety. 
 
8.11. 
Treatment of adverse events 
 
Treatment of any adverse event is at the sole discretion of the investigator and according 
to current good medical practice. Any medication administered for the treatment of an 
AE should be recorded in the subject's eCRF. Refer to Section 6.9. 
 
9. 
SUBJECT COMPLETION AND WITHDRAWAL 
 
9.1. 
Subject  completion 
 
A subject who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study. 
 
9.2. 
Subject  withdrawal 
 
Subjects who are withdrawn because of AEs must be clearly distinguished from subjects 
who are withdrawn for other reasons. Investigators will follow subjects who are 
withdrawn as result of a SAE/AE until resolution of the event (see Section 8.5.3). 
 
Withdrawals will not be replaced. 

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9.2.1. 
Subject withdrawal from the study 
 
From an analysis perspective, a 'withdrawal' from the study is any subject who did not 
come back for the concluding visit foreseen in the protocol. 
 
A subject qualifies as a 'withdrawal' from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact. 
 
Investigators will make an attempt to contact those subjects who do not return for 
scheduled visits or follow-up. 
 
Information relative to the withdrawal will be documented on the Study Conclusion page 
of the eCRF. The investigator will document whether the decision to withdraw from the 
study was made by the subject or the investigator and which of the following possible 
reasons was responsible for withdrawal: 
 
• 
serious adverse event 
• 
non-serious adverse event 
• 
protocol violation (specify) 
• 
consent withdrawal, not due to an adverse event 
• 
moved from the study area 
• 
lost to follow-up 
• 
other (specify). 
 
9.2.2. 
Subject withdrawal from investigational product 
 
A 'withdrawal' from the investigational product is any subject who does not receive the 
complete treatment, i.e. when no further planned vaccine is administered from the date of 
withdrawal. A subject withdrawn from the investigational product may not necessarily be 
withdrawn from the study as further study procedures or follow-up may be performed 
(safety or immunogenicity) if planned in the study protocol. 
 
Information relative to premature discontinuation of the investigational product will be 
documented on the Vaccine Administration page of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination was made by the 
subject or the investigator and which of the following possible reasons was responsible 
for withdrawal: 
 
• 
serious adverse event, 
• 
non-serious adverse event, 
• 
other (specify). 

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9.3. 
Screen and baseline failures 
 
Screening tests and evaluations (as described in Sections 5.4 and 5.5) will be used to 
determine the eligibility of each subject for the study. All inclusion and exclusion criteria 
must be assessed within 56 days (8 weeks) prior to study entry. Subjects who do not fulfil 
the conditions for being included in the study will be considered as screen failures and 
will be replaced. Screening failure subjects will be recorded with demographic data and 
reason for failure. 
 
10. 
DATA EVALUATION: CRITERIA FOR EVALUATION OF 
OBJECTIVES 
 
10.1. 
Primary  endpoints 
 
Reactogenicity and safety 
 
• 
Occurrence, intensity and relationship to vaccination of solicited local and general 
symptoms during a 7-day (Day 0 to Day 6) follow-up period after each vaccination. 
• 
Occurrence, intensity and relationship to vaccination of unsolicited symptoms during 
a 30-day (Day 0 to Day 29) follow-up period after each vaccination. 
• 
Occurrence and relationship to vaccination of serious adverse events during the 
whole study period. 
• 
Haematological and biochemical levels at months 0, 1, 2, 6, 7 9, 12 and at Day 44 
(two weeks after the second vaccination) in all subjects.(Amended September 24, 
2007) 
Immunogenicity 
 
• 
Frequency of CD4+ T cells expressing at least two cytokines including IL-2 equal or 
above the cut-off to at least 1, 2, 3 antigens and to all 4 antigens at Day 44 (two 
weeks after the second vaccination). 
 
10.2. 
Secondary  endpoints 
 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). (Amended September 24, 
2007) 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing at least 2 
cytokines including IL-2 equal or above the cut-off at Months 0, 2, 6, 7, 12 and at 
Day 44 (two weeks after the second vaccination). (Amended September 24, 2007) 
• 
Antibody titers to p17, p24, Nef, RT and F4co as measured by ELISA at Months 0, 
2, 6, 7, 12 and at Day 44 (two weeks after the second vaccination). (Amended 
September 24, 2007) 

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10.3. 
Exploratory  endpoints 
 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells to other HIV clades 
expressing IL-2 and/or TNF-and/or IFN-and/or CD40-L, as determined by ICS at 
Day 44 (two weeks after the second vaccination) and/or at Month 2. 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). (Amended September 24, 
2007) 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing at least 2 
cytokines (IL-2 and/or TNF-and/or IFN-and/or CD40-L) equal or above the cut- 
off at Months 0, 2, 6, 7, 12 and at Day 44 (two weeks after the second vaccination). 
(Amended September 24, 2007) 
 
10.4. 
Estimated sample size 
 
As this study is a first evaluation of safety and immunogenicity of the HIV candidate 
vaccine F4co, no formal sample size determination has been performed. 
 
However, Table 11 presents the precision achieved for estimation of the primary 
parameters. 
 
Table 11 
Precision achieved for different estimated proportions and for the 
two sample sizes of 10 and 50 subjects [by PASS 2005, 95% 
confidence interval of a proportion]. 
 
Estimated 
proportion 
Precision 
N=50 
Precision 
N=10 
0.20 or 0.80 
0.10 
0.20 
0.40 or 0.60 
0.14 
0.30 
 
If we want to compare the three adjuvanted groups in terms of proportion of subjects with 
a given adverse event or in terms of proportion of responders to a vaccine antigen, the 
sample size of 50 subjects per group would achieve 80% power to detect around 20-30% 
difference in proportions with a two-sided alpha level of 0.0167 (Bonferroni's adjustment 
for 3 comparisons) (see Table 12). 

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Table 12 
Difference between 2 groups of 50 subjects that can be detected 
with a power of 80% (two-sided alpha of 0.0167 for multiple 
comparisons between three groups) (by PASS 2005, two 
independent proportions, Fisher’s Exact test) 
 
Proportion in group 1 Proportion in group 2 
Difference in proportions 
0.10 
0.38 
0.28 
0.20 
0.52 
0.32 
0.30 
0.63 
0.33 
0.40 
0.73 
0.33 
0.50 
0.82 
0.32 
0.60 
0.89 
0.29 
0.70 
0.95 
0.25 
0.80 
0.99 
0.19 
 
10.5. 
Study cohorts to be evaluated 
 
Total Vaccinated cohort 
 
The Total Vaccinated cohort will include all vaccinated subjects. 
 
Thus, the Total Vaccinated cohort for analysis of safety will include all subjects with at 
least one vaccine administration documented. 
 
The Total Vaccinated cohort for analysis of immunogenicity will include vaccinated 
subjects for whom data concerning immunogenicity endpoint measures are available. 
 
The Total Vaccinated cohort analysis will be performed per treatment actually 
administered. 
 
According-To-Protocol (ATP) cohort for analysis of safety 
The ATP cohort will include all vaccinated subjects 
 
• who have received at least one dose of study vaccine according to their random 
assignment 
• with sufficient data to perform an analysis of safety (at least one dose with safety 
follow-up) 
• for whom administration route of study vaccines is known 
• who have not received a vaccine not specified or forbidden in the protocol 
• for whom the randomization code has not been broken. 

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According To Protocol (ATP) cohort for analysis of immunogenicity 
The ATP cohort for analysis of immunogenicity will include all evaluable subjects, (i.e., 
those meeting all eligibility criteria, complying with the procedures and intervals defined 
in the protocol, with no elimination criteria during the study) for whom data concerning 
immunogenicity endpoint measures are available. 
 
10.6. 
Derived and transformed data 
 
Serology data 
 
• The cut-off values for antibody titers will be defined by the laboratory before the 
analysis. 
• A seronegative subject is a subject whose titer is below the cut-off value. 
• A seropositive subject is a subject whose titer is greater than or equal to the cut-off 
value. 
• The seropositivity rate is defined as the percentage of seropositive subjects. 
• The Geometric Mean Titers (GMTs) calculations will be performed by taking the 
anti-log of the mean of the log titer transformations. Antibody titers below the cut-off 
of the assay will be given an arbitrary value of half the cut-off for the purpose of 
GMT calculation. 
 
JCSdata 
 
• ICS data will be expressed as antigen-specific CD4/CD8 T-cells per million 
respectively of CD4 or CD8+ T-cells. 
 
• The cut-off will be calculated by taking the 95 percentile of the pre-vaccination data 
of all subjects. 
 
• A responder is a subject with antigen-specific CD4/CD8 T-cells response greater than 
or equal to the cut-off value. 
 
• Frequency of CD4/CD8 T-cells expressing cytokines to the fusion protein F4co (all 
antigens) will be estimated by adding individual frequencies of CD4/CD8 T-cells to 
each 4 antigens (p17, p24, Nef, RT). 
 
Handling of missing 
 
• 
For a given subject and a given immunogenicity measurement, missing or non- 
evaluable measurements will not be replaced. 
• 
For the calculation of percentage of responders to 1, 2, 3 and all 4 antigens, subjects 
not responding to at least one of the concerned antigen(s) will not be taken into 
account. 
• 
For the analysis of solicited symptom, missing or non-evaluable measurements will 
not be replaced. Therefore the analysis of the solicited symptoms based on the total 

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vaccinated cohort will include only injections with documented safety data (i.e. 
symptomscreen/sheet completed). 
• 
For the analysis of unsolicited adverse events/serious adverse event/concomitant 
medication, all vaccinated subjects will be considered and subjects who did not 
report an event will be considered as subjects without an event. 
 
10.7. 
Final analyses 
 
10.7.1. 
Analysis of demographics/baseline characteristics 
 
Demographic characteristics (age, gender, race) of each study cohort will be tabulated. 
 
The mean age (plus range and standard deviation) by gender of the enrolled subjects, as a 
whole, and per group, will be calculated. 
 
10.7.2. 
Analysis of immunogenicity 
 
The primary analysis will be based on the ATP cohort for analysis of immunogenicity. If 
the percent of enrolled subjects excluded from this ATP cohort is more than 5%, a second 
analysis based on the Total Vaccinated cohort will be performed to complement the ATP 
analysis. 
 
Cell-mediated immune response 
 
For cell-mediated immune response, the following parameters will be tabulated by 
vaccine groups at months 0, 2, 6, 7, 12 and at day 44 (two weeks after the second 
vaccination)(Amended September 24, 2007): 
 
• 
descriptive statistics of the frequency of CD4/CD8 T cell expressing at least two 
different cytokines (IFN-, IL-2, TNF-,CD40L) to each antigen and to all antigens; 
• 
descriptive statistics of the frequency of CD4/CD8 T cell expressing at least IFN- 
and another cytokine (IL-2, TNF-,CD40L) to each antigen and to all antigens; 
• 
descriptive statistics of the frequency of CD4/CD8 T cell expressing at least IL-2 and 
another cytokine (IFN-, TNF-,CD40L) to each antigen and to all antigens; 
• 
descriptive statistics of the frequency of CD4/CD8 T cell expressing at least TNF- 
and another cytokine (IFN-, IL-2,CD40L) to each antigen and to all antigens; 
• 
descriptive statistics of the frequency of CD4 T cell expressing at least CD40L and 
another cytokine (IFN-, IL-2, TNF-) to each antigen and to all antigens. 
CD4+ T-cells expressing JL-2 and another cytokine 
 
For CD4+ T-cells expressing IL-2 and another cytokine response, the following 
parameters will be tabulated by vaccine groups at months 0, 2, 6, 7, 12 and at day 44 (two 
weeks after the second vaccination) (Amended September 24, 2007): 
 
• 
percentage of responders to each antigen (p17, p24, Nef, RT); 

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• 
percentage of responders to at least one antigen (p17, p24, Nef or RT); 
• 
percentage of responders to at least two antigens; 
• 
percentage of responders to at least three antigens; 
• 
percentage of responders to all four antigens (p17, p24, Nef and RT). 
CDS+ T-cells expressing at least 2 cytokines (IL-2 and/or TNF-and/or IFN-and/or 
CD40-L) 
 
For CD8+ T-cells expressing at least 2 cytokines, percentage of responders to each 
antigen (p17, p24, Nef, RT) will be tabulated by vaccine groups at months 0, 2, 6, 7, 12 
and at day 44 (two weeks after the second vaccination). (Amended September 24, 2007) 
 
Humoral immune response 
 
For humoral immune response, the following parameters will be tabulated by vaccine 
groups for each antigen (p17, p24, Nef, RT and F4co) at months 0, 2, 6, 7, 12 and at day 
44 (two weeks after the second vaccination) (Amended September 24, 2007): 
 
• 
Geometric mean titers (GMTs) with 95% confidence intervals (CIs); 
• 
Seropositivity rates with exact 95% CIs. 
 
10.7.3. 
Analysis of safety 
 
The primary analysis will be based on the Total Vaccinated cohort. If the percent of 
enrolled subjects excluded from the ATP cohort for analysis is more than 5%, a second 
analysis based on this ATP cohort will be performed to complement the total analysis. 
 
Adverse events 
 
The following parameters will be tabulated per treatment group: 
 
• 
The percentage of subjects with at least one local AE (solicited and unsolicited), with 
at least one general AE (solicited and unsolicited) and with any AE during the 
solicited follow-up period will be tabulated with exact 95% confidence interval (CI) 
after each vaccine injection and overall. 
• 
The percentage of vaccine injections followed by at least one local AE (solicited and 
unsolicited), by at least one general AE (solicited and unsolicited) and by any AE 
will be tabulated, overall vaccination course, with exact 95% CI. 
• 
The percentage of subjects reporting each individual solicited local and general AE 
during the solicited follow-up period will be tabulated with exact 95% CI. 
• 
The percentage of vaccine injections followed by each individual solicited local and 
general AE will be tabulated, overall vaccination course, with exact 95% CI. 
• 
The proportion of subjects with at least one report of unsolicited AE classified by the 
Medical Dictionary for Regulatory Activities (MedDRA) and reported up to 30 days 
after vaccination will be tabulated with exact 95% CI. 

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The same tabulations will be done for grade 3 adverse events and/or for adverse events 
with relationship to vaccination. 
 
Fever will be reported per 0.5°C cumulative increments. 
 
Serious AEs and withdrawal due to AEs will be described in detail. 
 
Haematological and biochemical parameters 
 
The frequency distribution of values below, within and above normal ranges will be 
tabulated per treatment group at each scheduled time point. 
 
10.8. 
Planned interim analyses 
 
Safety interim analyses 
 
Nine Six interim analyses are planned for safety evaluation (see Section 5.6). 
 
These analyses will be performed at the end of the 7-day follow-up period (Days 7, and 
37 and 187) after each vaccine injection in a subset of 12 subjects and for each vaccine 
dose (10, 30 and 90 g).(Amended September 24, 2007) 
 
Analysis will be done on uncleaned and blinded data. Individual data listings of the 
demographic and safety data (solicited/unsolicited AE, SAE, haematology and 
biochemistry values) will be provided to the SRT. Tables with the number of subjects 
responding to each stopping rules will be also provided. 
 
Analyses will be performed by an external statistician if unblinding of data is required. 
Individual data listings and tables will then be provided to an internal data monitoring 
committee. 
 
No clinical report will be written. 
 
Final analyses 
 
Final analyses will be performed by groups on cleaned data and in three two steps. 
 
• 
A first analysis will be performed when all data up to and including month 2 
(immogenicity and safety) will be available. 
 • 
A second analysis will be performed when all data up to and including month 7 
(immogenicity and safety) will be available. 
• 
A third second analysis will be performed and a clinical report will be written at the 
completion of the study. (Amended September 24, 2007) 

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11. 
ADMINISTRATIVE MATTERS 
To comply with Good Clinical Practice important administrative obligations relating to 
investigator responsibilities, monitoring, archiving data, audits, confidentiality and 
publications must be fulfilled. See Appendix B for details. 

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12. 
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Appendix A World Medical Association Declaration of Helsinki 
 
Recommendations guiding physicians 
in biomedical research involving human subjects 
Adopted by the 18th World Medical Assembly 
Helsinki, Finland, June 1964 
 
and amended by the 
29th World Medical Assembly 
Tokyo, Japan, October 1975 
35th World Medical Assembly 
Venice, Italy, October 1983 
41st World Medical Assembly 
Hong Kong, September 1989 
and the 
48th General Assembly 
Somerset West, Republic of South Africa, October 1996 
INTRODUCTION 
It is the mission of the physician to safeguard the health of the people. His or her 
knowledge and conscience are dedicated to the fulfilment of this mission. 
 
The Declaration of Geneva of the World Medical Association binds the physician with 
the words, "The health of my patient will be my first consideration," and the International 
Code of Medical Ethics declares that, "A physician shall act only in the patient's interest 
when providing medical care which might have the effect of weakening the physical and 
mental condition of the patient." 
 
The purpose of biomedical research involving human subjects must be to improve 
diagnostic, therapeutic and prophylactic procedures and the understanding of the etiology 
and pathogenesis of disease. 
 
In current medical practice most diagnostic, therapeutic or prophylactic procedures 
involve hazards. This applies especially to biomedical research. 
 
Medical progress is based on research which ultimately must rest in part on 
experimentation involving human subjects. 
 
In the field of biomedical research a fundamental distinction must be recognized between 
medical research in which the aim is essentially diagnostic or therapeutic for a patient, 
and medical research, the essential object of which is purely scientific and without 
implying direct diagnostic or therapeutic value to the person subjected to the research. 
 
Special caution must be exercised in the conduct of research which may affect the 
environment, and the welfare of animals used for research must be respected. 

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Because it is essential that the results of laboratory experiments be applied to human 
beings to further scientific knowledge and to help suffering humanity, the World Medical 
Association has prepared the following recommendations as a guide to every physician in 
biomedical research involving human subjects. They should be kept under review in the 
future. It must be stressed that the standards as drafted are only a guide to physicians all 
over the world. Physicians are not relieved from criminal, civil and ethical 
responsibilities under the laws of their own countries. 
 
I. 
BASIC PRINCIPLES 
 
1. Biomedical research involving human subjects must conform to generally accepted 
scientific principles and should be based on adequately performed laboratory and 
animal experimentation and on a thorough knowledge of the scientific literature. 
2. The design and performance of each experimental procedure involving human 
subjects should be clearly formulated in an experimental protocol which should be 
transmitted for consideration, comment and guidance to a specially appointed 
committee independent of the investigator and the sponsor provided that this 
independent committee is in conformity with the laws and regulations of the country 
in which the research experiment is performed. 
3. Biomedical research involving human subjects should be conducted only by 
scientifically qualified persons and under the supervision of a clinically competent 
medical person. The responsibility for the human subject must always rest with a 
medically qualified person and never rest on the subject of research, even though the 
subject has given his or her consent. 
4. Biomedical research involving human subjects cannot legitimately be carried out 
unless the importance of the objective is in proportion to the inherent risk to the 
subject. 
5. Every biomedical research project involving human subjects should be preceded by 
careful assessment of predictable risks in comparison with foreseeable benefits to the 
subject or to others. Concern for the interests of the subject must always prevail over 
the interests of science and society. 
6. The right of the research subject to safeguard his or her integrity must always be 
respected. Every precaution should be taken to respect the privacy of the subject and 
to minimize the impact of the study on the subject's physical and mental integrity and 
on the personality of the subject. 
7. Physicians should abstain from engaging in research projects involving human 
subjects unless they are satisfied that the hazards involved are believed to be 
predictable. Physicians should cease any investigation if the hazards are found to 
outweigh the potential benefits. 
8. In publication of the results of his or her research, the physician is obliged to 
preserve the accuracy of the results. Reports of experimentation not in accordance 
with the principles laid down in this Declaration should not be accepted for 
publication. 

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9. In any research on human beings, each potential subject must be adequately 
informed of the aims, methods, anticipated benefits and potential hazards of the 
study and the discomfort it may entail. He or she should be informed that he or she is 
at liberty to abstain from participation in the study and that he or she is free to 
withdraw his or her consent to participation at any time. The physician should then 
obtain the subject's freely-given informed consent, preferably in writing. 
10. When obtaining informed consent for the research project the physician should be 
particularly cautious if the subject is in a dependent relationship to him or her or may 
consent under duress. In that case the informed consent should be obtained by a 
physician who is not engaged in the investigation and who is completely independent 
of this official relationship. 
11. In case of legal incompetence, informed consent should be obtained from the legal 
guardian in accordance with national legislation. Where physical or mental 
incapacity makes it impossible to obtain informed consent, or when the subject is a 
minor, permission from the responsible relative replaces that of the subject in 
accordance with national legislation. 
Whenever the minor child is in fact able to give a consent, the minor's consent must 
be obtained in addition to the consent of the minor's legal guardian. 
12. The research protocol should always contain a statement of the ethical considerations 
involved and should indicate that the principles enunciated in the present Declaration 
are complied with. 
II. 
MEDICAL RESEARCH COMBINED WITH PROFESSIONAL CARE 
(Clinical research) 
 
1. In the treatment of the sick person, the physician must be free to use a new 
diagnostic and therapeutic measure, if in his or her judgement it offers hope of 
saving life, re-establishing health or alleviating suffering. 
2. The potential benefits, hazards and discomfort of a new method should be weighed 
against the advantages of the best current diagnostic and therapeutic methods. 
3. In any medical study, every patient - including those of a control group, if any - 
should be assured of the best proven diagnostic and therapeutic method. This does 
not exclude the use of inert placebo in studies where no proven diagnostic or 
therapeutic method exists. 
4. The refusal of the patient to participate in a study must never interfere with the 
physician--patient  relationship. 
5. If the physician considers it essential not to obtain informed consent, the specific 
reasons for this proposal should be stated in the experimental protocol for 
transmission to the independent committee (I, 2). 
6. The Physician can combine medical research with professional care, the objective 
being the acquisition of new medical knowledge, only to the extent that medical 
research is justified by its potential diagnostic or therapeutic value for the patient. 

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III. 
NON-THERAPEUTIC BIOMEDICAL RESEARCH INVOLVING HUMAN 
SUBJECTS (Non-clinical biomedical research) 
 
1. In the purely scientific application of medical research carried out on a human being, 
it is the duty of the physician to remain the protector of the life and health of that 
person on whom biomedical research is being carried out. 
2. The subjects should be volunteers - either healthy persons or patients for whom the 
experimental design is not related to the patient's illness. 
3. The investigator or the investigating team should discontinue the research if in 
his1her or their judgement it may, if continued, be harmful to the individual. 
In research on man, the interest of science and society should never take precedence over 
considerations related to the well being of the subject. 

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Appendix B Administrative Matters 
 
I. 
Responsibilities of the Investigator 
 
• 
To ensure that he/she has sufficient time to conduct and complete the study and has 
adequate staff and appropriate facilities and equipment which are available for the 
duration of the study and to ensure that other studies do not divert essential subjects 
or facilities away from the study at hand. 
• 
To submit an up-to-date curriculum vitae or Investigator Biography and other 
credentials (e.g., medical license number in the United States) to GSK and-where 
required-to relevant authorities. It is recommended that this documentation 
indicates any previous clinical research experience and history of training in GCP. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory's current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on site or 
elsewhere without the approval of GSK Biologicals and the express written informed 
consent of the subject and/or the subject's legally authorized representative. 
• 
To perform no other biological assays at the investigator site except those described 
in the protocol or its amendment(s). 
• 
To prepare and maintain adequate subject source data or raw data designed to record 
observations, and other data pertinent to the study. 
• 
To conduct the study in compliance with the protocol any amendment and "Good 
Clinical Practice" (GCP) and all applicable regulatory requirements. 
• 
To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data. 
• 
To permit drug regulatory agencies and GSK audits. 
II. 
Protocol Amendments and Administrative changes 
 
• 
No changes to the study protocol will be allowed unless discussed in detail with the 
GSK Biologicals' Clinical Development Manager/Medical Monitor and filed as an 
amendment/administrative change to this protocol. 
• 
Any amendment/administrative change to the protocol will be adhered to by the 
participating center(s) and will apply to all subjects. Written IRB/IEC approval of 
protocol amendments is required prior to implementation, except where permitted by 
all applicable regulatory requirements; administrative changes and amendments not 
submitted for approval are submitted to IRBs/IECs for information only. 
• 
Submission of protocol amendments to regulatory agencies will occur in accordance 
with local regulatory requirements. For some countries, submission to the local 
regulatory authority may not be required. When submission to the local regulatory 
authority is required, the timing of the submission relative to IEC/IRB submission or 
approval and whether or not the authority will provide their approval of or 

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favourable opinion on the amendment before it can be implemented will depend on 
local regulatory requirements. 
III. 
Sponsor’s Termination of Study 
 
GSK Biologicals reserves the right to temporarily suspend or prematurely discontinue 
this study either at a single site or at all sites at any time for reasons including, but not 
limited to, safety or ethical issues or severe non-compliance. Reasons for suspension or 
early termination will be documented in the study file at GSK Biologicals. 
 
If GSK Biologicals determines that suspension or early termination is needed, GSK 
Biologicals will discuss this with the Investigator (including the reasons for taking such 
action). When feasible, GSK Biologicals will provide advance notification to the 
investigator of the impending action prior to it taking effect. 
 
GSK Biologicals will promptly inform, via written communication, all investigators 
and/or institutions conducting the study, if the study is suspended or terminated for safety 
reasons, and will also inform the regulatory authorities of the suspension or termination 
of the study and the reason(s) for the action. If required by applicable regulations, the 
investigator must inform the IEC/IRB promptly and provide the reason for the suspension 
or termination. 
 
If the study is prematurely discontinued, all study data must be returned to GSK. In 
addition, arrangements will be made for all unused investigational product(s) in 
accordance with the applicable GSK procedures for the study. Financial compensation to 
investigators and/or institutions will be in accordance with the agreement established 
between the investigator and/or institutions and GSK. 
 
IV. 
Case Report Form Instructions / Remote Data Entry Instructions 
 
Remote Data Entry (RDE) will be used as the method for data collection, which means 
that subject information will be entered into a computer at the investigational site. The 
site will be capable of modifying the data to assure accuracy with source documentation. 
All new/updated information will be reviewed and verified by a GSK Biologicals' 
representative. This information will finally be stored in a central database maintained by 
GSK Biologicals. At the conclusion of the study, GSK Biologicals will archive the study 
data in accordance with internal procedures. In addition, the investigator will be provided 
with a CD-ROM of the final version of the data generated at the investigational site. 
 
Specific instructions for use of RDE will be included in the training material provided to 
the investigational site. 
 
V. 
Monitoring by GSK Biologicals 
 
To ensure compliance with the protocol, monitoring visits by a professional 
representative of the sponsor will be scheduled to take place early in the study, during the 
study at appropriate intervals and after the last subject has completed the study. It is 
anticipated that monitoring visits will occur at a frequency defined and communicated to 
the investigator before study start. 

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These visits are for the purpose of confirming that GSK Biologicals' sponsored studies 
are being conducted in accordance with the ethical principles that have their origins in the 
Declaration of Helsinki and that are consistent with Good Clinical practice (GCP) and the 
applicable regulatory requirement(s) (verifying continuing compliance with the protocol, 
amendment(s), reviewing the investigational product accountability records, verifying 
that the site staff and facilities continue to be adequate to conduct the study. Direct access 
to all study-related site and source data/ documents is mandatory for the purpose of 
monitoring review. The monitor will perform a eCRF review and a Source Document 
verification (verifying eCRF/ RDE entries by comparing them with the source 
data/documents that will be made available by the investigator for this purpose: any data 
item for which the eCRF will serve as the source must be identified, agreed and 
documented. Data to be recorded directly into the eCRF pages/RDE screens will be 
specified in writing preferably in the source documentation agreement form that is 
contained in both the monitor's and investigator's study file. For RDE, the monitor will 
mark completed and approved screens at each visit. The investigator must ensure 
provision of reasonable time, space and adequate qualified personnel for monitoring 
visits. Source data verification (SDV) must be conducted using a GSK standard SDV 
sampling strategy (as defined at the study start in the study specific monitoring 
guidelines) in which monitors will perform partial SDV for all subjects and full SDV for 
selected subjects. 
 
VI. 
Archiving of Data 
 
Following closure of the study, the investigator must maintain all site study records in a 
safe and secure location. The records must be maintained to allow easy and timely 
retrieval, when needed (e.g., audit or inspection), and, whenever feasible, to allow any 
subsequent review of data in conjunction with assessment of the facility, supporting 
systems, and staff. Where permitted by applicable laws/regulations or institutional 
policy, some or all of these records can be maintained in a validated format other than 
hard copy (e.g., microfiche, scanned, electronic for studies with an eCRF, for example); 
however, caution needs to be exercised before such action is taken. The investigator must 
assure that all reproductions are legible and are a true and accurate copy of the original, 
and meet accessibility and retrieval standards, including re-generating a hard copy, if 
required. Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions. 
 
GSK will inform the investigator/ institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. However, the investigator/ 
institution should seek the written approval of the sponsor before proceeding with the 
disposal of these records. The minimum retention time will meet the strictest standard 
applicable to that site for the study, as dictated by ICH GCP E6 Section 4.9, any 
institutional requirements or applicable laws or regulations, or GSK 
standards/procedures; otherwise, the minimum retention period will default to 15 years. 
 
The investigator/ institution must notify GSK of any changes in the archival 
arrangements, including, but not limited to, the following: archival at an off-site facility, 
transfer of ownership of the records in the event the investigator leaves the site. 

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VII. 
Audits 
 
For the purpose of compliance with Good Clinical Practice and Regulatory Agency 
Guidelines it may be necessary for GSK or a Drug Regulatory Agency to conduct a site 
audit. This may occur at any time from start to after conclusion of the study. 
 
When an investigator signs the protocol, he agrees to permit drug regulatory agencies and 
GSK audits, providing direct access to source data/ documents. Furthermore, if an 
investigator refuses an inspection, his data will not be accepted in support of a New Drug 
Registration and/or Application, Biologics Licensing Application. 
 
Having the highest quality data and studies are essential aspects of vaccine development. 
GSK has a Regulatory Compliance staff who audit investigational sites. Regulatory 
Compliance assesses the quality of data with regard to accuracy, adequacy and 
consistency. In addition, Regulatory Compliance assures that GSK Biologicals' 
sponsored studies are in accordance with GCP and that relevant regulations/guidelines are 
being followed. 
 
To accomplish these functions, Regulatory Compliance selects investigational sites to 
audit. These audits usually take 1 to 2 days. GSK's audits entail review of source 
documents supporting the adequacy and accuracy of eCRFs, review of documentation 
required to be maintained, and checks on vaccine accountability. GSK's audit therefore 
helps prepare an investigator for a possible regulatory agency inspection as well as 
assuring GSK Biologicals of the validity of the database across investigational sites. 
 
The Inspector will be especially interested in the following items: 
 
• 
Log of visits from the sponsor's representatives 
• 
Study personnel 
• 
Study file 
• 
Safety reporting 
• 
IRB/IEC and regulatory authorityapprovals 
• 
Facilities 
• 
monitoring 
• 
Vaccine accountability 
• 
Approved study protocol and amendments and Investigator's Brochure 
• 
Informed consent of the subjects (written consent or witnessed oral if applicable) 
• 
Medical records and other source documents supportive of eCRF data 
• 
Reports to the IRB/IEC and the sponsor 
• 
Record retention. 
GSK Biologicals will gladly help investigators prepare for an inspection. 

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VIII. 
Ownership, Confidentiality and Publication 
 
Ownership: 
All information provided by GSK and all data and information generated by the site as 
part of the study (other than a subject's medical records) are the sole property of GSK. 
 
All rights, title, and interests in any inventions, know-how or other intellectual or 
industrial property rights which are conceived or reduced to practice by site staff during 
the course of or as a result of the study are the sole property of GSK, and are hereby 
assigned to GSK. 
 
If a written contract for the conduct of the study which includes ownership provisions 
inconsistent with this statement is executed between GSK and the study site, that 
contract's ownership provisions shall apply rather than this statement. 
 
Confidentiality: 
Documented evidence that a potential investigator is aware and agrees to the confidential 
nature of the information related to the study must be obtained by means of a 
confidentiality agreement. 
 
All information provided by GSK and all data and information generated by the site as 
part of the study (other than a subject's medical records) will be kept confidential by the 
investigator and other site staff. This information and data will not be used by the 
investigator or other site personnel for any purpose other than conducting the study. 
These restrictions do not apply to: (1) information which becomes publicly available 
through no fault of the investigator or site staff; (2) information which it is necessary to 
disclose in confidence to an IEC or IRB solely for the evaluation of the study; (3) 
information which it is necessary to disclose in order to provide appropriate medical care 
to a study subject; or (4) study results which may be published as described in the next 
paragraph. If a written contract for the conduct of the study which includes 
confidentiality provisions inconsistent with this statement is executed, that contract's 
confidentiality provisions shall apply rather than this statement. 
 
Publication: 
For multicenter studies, the first publication or disclosure of study results shall be a 
complete, joint multicenter publication or disclosure coordinated by GSK. Thereafter, 
any secondary publications will reference the original publication(s). 
 
Prior to submitting for publication, presentation, use for instructional purposes, or 
otherwise disclosing the study results generated by the site (collectively, a "Publication"), 
the investigator shall provide GSK with a copy of the proposed Publication and allow 
GSK a period to review the proposed Publication (at least 21 (twenty-one) days [or at 
least 15 (fifteen) working days for abstracts/posters/presentations]. Proposed Publications 
shall not include either GSK confidential information other than the study results or 
personal data on any subject, such as name or initials. 
 
At GSK's request, the submission or other disclosure of a proposed Publication will be 
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inventions, know-how or other intellectual or industrial property rights disclosed in the 
proposed Publication. 
 
If a written contract for the conduct of the study, which includes publication provisions 
inconsistent with this statement is executed, that contract's publication provisions shall 
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Appendix C Overview of the Recruitment Plan 
 
The investigator may use one of the following strategies for recruiting volunteers: 
 
• 
Advertising / posters inside Ghent University Hospital buildings 
• 
Group meetings 
• 
University and Hospital personnel and students 
• 
E-mails to the existing volunteers 
• 
Recruitment via the center's website http://www.cevac.be 
• 
If needed: advertisement (via an interview with an investigator) in the 
regional/Flemish written and spoken media. 
At the study center, subjects will be screened for admission criteria and the first 180 
subjects who meet all inclusion/exclusion criteria will be enrolled and allocated a 
randomization number according to the order in which they are enrolled. 
 
The enrollment period, i.e., the period between the study start and the last enrolled 
subject, is maximum 20 weeks. This will be followed by the study monitor. 
 
The recruitment plan must be discussed and defined with the Investigator by the Site 
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Appendix D Handling of Biological Samples Collected by the Investigator 
 
Instructions for Handling of Serum Samples 
 
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) will be collected and stored using exclusively those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis. The investigator must ensure that his/her 
personnel and the laboratory(ies) under his/her supervision comply with this requirement. 
However, when GSK Biologicals does not provide material for collecting and storing 
clinical samples, then appropriate materials from the investigator's site are to be used. 
 
1. Collection 
The whole blood (by capillary or venous route) should be collected observing appropriate 
aseptic conditions. It is recommended that Vacutainertubes WITH integrated serum 
separator (e.g. Becton-Dickinson VacutainerSST or CorvacSherwood Medical) be 
used to minimize the risk of haemolysis and to avoid blood cell contamination of the 
serum when transferring to standard serum tubes. 
 
2. Serum separation 
These guidelines aim to ensure high quality serum by minimizing the risk of haemolysis, 
blood cell contamination of the serum or serum adverse cell toxicity at testing. 
 
• 
For separation of serum using Vacutainer® tubes, the instructions provided by the 
manufacturer should be followed. Often the manufacturer's instruction states that the 
relative centrifugal acceleration known also as "G" must be "between 1000 and 1300 
G" with tubes spinning for ten minutes. Error in calculation of centrifuge speed can 
occur when laboratory personnel confuse "G" acceleration with "RPM" (revolutions 
per minute). The speed of centrifugation must be calculated using the "G" rate 
provided in the manufacturer's instructions and the radius of the centrifuge head. 
After measuring the radius of the centrifuge machine, a speed/acceleration 
nomograph must be employed to determine the centrifuge speed in "RPM". 
• 
Following separation, the serum should be aseptically transferred to the appropriate 
standard tubes using a sterile disposable pipette. The serum should be transferred as 
gently as possible to avoid blood cell contamination. 
• 
The tube should not be overfilled (max. 314 of the total volume) to allow room for 
expansion upon freezing. 
• 
The tube should be identified by the appropriate label provided by GSK Biologicals 
(see point 3). 
3. Labelling 
• 
The standard labels provided by GSK Biologicals should be used to label each serum 
sample. 
• 
If necessary, any hand-written additions to the labels should be made using indelible 
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• 
The label should be attached to the tube as follows (see diagram): 
 first attach the paper part of the label to the tube 
 then wrap the label around the tube so that the transparent, plastic part of the 
label overlaps with the label text and bar code and shields them. 
This will ensure optimal label attachment. 
 
 
Plastic, transparent part 
 
  
 
Paper, text part 
 
 
• 
Labels should not be attached to caps. 
4. Sorting and storage 
• 
Tubes should be placed in the GSK Biologicals' cardboard boxes in numerical order 
from left to right, starting from the lower left hand corner, beginning with the pre- 
vaccination samples series, then with the post-vaccination sample series. 
• 
The tubes of serum should be stored in a vertical position at approximately -20°C 
(alternatively at approximately -70°180°C is also acceptable) until shipment to GSK 
Biologicals. The storage temperature should be checked regularly and documented. 
Wherever possible, a backup facility for storage of serum samples should be 
available. 
• 
A standard Serum Listing Form, specifying the samples being shipped for individual 
subjects at each timepoint, should be prepared for each shipment. A copy of this list 
should be retained at the study site, while the original should be sealed in a plastic 
envelope and shipped with the serum samples. 
Study N°......... 
Subject N° ...... 
POST VACC. I 
STUDY MTH 1 
For GlaxoSmithKline 
Biologicals 
Bar code 

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R & D Department/Building 44 
Rue de l'Institut, 89 
B-1330 Rixensart 
+32-2-656 8949 or +32-2-656 6130 
or +32-2-656 8549 or +32-2-656 6108 
Fax: 
+32-2-656 6052 
rix.ugbiospecimen-reception@gskbio.com 
• 
Once shipment details are known, a standard Specimen Transfer Form must be 
completed and faxed to GSK Biologicals to the number provided below. A copy of 
the Specimen Transfer Form must be in the parcel.1 
GLAXOSMITHKLINE BIOLOGICALS 
 
Attention Biospecimen Reception 
Clinical Immunology 
 
Telephone: 
PPD 
PPD 
 
E-mail: PPD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PPD 
PPD 
- Belgium 

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Instructions for Handling Cells for Cell-Mediated Immunity Assay 
 
When materials are provided by GSK Biologicals, it is mandatory that all clinical 
samples be collected and stored using exclusively those materials in the appropriate 
manner. The use of other materials could result in the exclusion of the subject from 
analysis. The investigator must ensure that his/her personnel and the laboratory(ies) under 
his/her supervision comply with this requirement. 
 
1. Collection of whole blood 
 
Collect blood by venipuncture in Terumo tubes with heparin (or equivalent) and record 
time of collection. The tubes should be kept at room temperature and shipped to a 
designated clinical site for separation of peripheral blood mononuclear cells (PBMCs). 
The shipment must be timed to ensure that PBMC separation will be performed within 24 
hours. Use well closed styrofoam boxes of 5 cm thickness for blood samples transport 
(see current version of GSK Biologicals SOP RD_HCI_001 for guidance). 
 
2. Separation and freezing of PBMCs 
 
PBMCs will be separated on a density gradient, aliquoted and frozen at --80°C for 24 
hours and further cryopreserved in liquid nitrogen until testing (see GSK Biologicals 
SOP: RD_HCI_007 for guidance). 
 
3. Labelling of cryotubes for PBMC samples 
 
• 
If labels are provided by GSK, it is mandatory to use them. 
• 
If necessary, any hand-written additions to the labels should be made using indelible 
ink. 
4. Sorting and storage of PBMC samples 
 
Samples should be stored in liquid nitrogen until shipment to GSK Biologicals, if needed. 
Wherever possible, a backup facility for storage of samples should be available. 
 
A standard Cryotube Listing Form (see current version of GSK Biologicals SOP 
RD_HCI_009 for guidance) specifying the samples being shipped for individual 
subjects at each timepoint, should be prepared for each shipment. A copy of this list 
should be retained at the study site, while the original should be sealed in a plastic 
envelope and shipped with the PBMC samples. 

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+32-2-656 8949 or +32-2-656 6130 
or +32-2-656 8549 or +32-2-656 6108 
rix.ugbiospecimen-reception@gskbio.com 
Fax: 
+32-2-656 6052 
Appendix E 
Shipment of Biological Samples 
 
Instructions for Shipment of Serum Samples 
 
Serum samples should be sent to GSK Biologicals at regular intervals. The frequency of 
shipment of samples should be decided upon by the Site Monitor, Central Study 
Coordinator and the investigator prior to the study start. 
 
Serum samples should always be sent by contract courier designated by the sponsor, 
unless otherwise requested by the sponsor. 
 
Serum samples must be placed with dry ice (maximum -20°C) in a container complying 
with International Air Transport Association (IATA)  requirements. The completed 
standard serum listing form should always accompany the shipment. 
 
The container must be clearly identified with the labels provided by GSK Biologicals 
specifying the shipment address and the storage temperature (-20°C). 
 
Details of the shipment, including: 
* 
number of samples 
* 
date of transfer 
should be sent by fax or by e-mail, two days before shipment, to: 
GLAXOSMITHKLINE BIOLOGICALS 
Attention Biospecimen Reception 
Clinical Immunology 
R & D Department/Building 44 
Rue de l'Institut, 89 
B-1330 Rixensart - Belgium 
Telephone: 
 
 
E-mail: 
PPD 
PPD 
PPD 
PPD 

CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
October 8, 2007 
c1d52d5169346976c392d219162efc7a 
107 
 
 
+32-2-656 8949 or +32-2-656 6130 
or +32-2-656 8549 or +32-2-656 6108 
PPD 
 
 
Instructions for Shipment of PBMC Samples 
 
Frozen PBMCs must be transported in liquid nitrogen in an appropriate dry shipper 
(ideally CP400 or equivalent containing up to 4 boxes of 100 cryovials). The dry shipper 
must be previously filled with liquid nitrogen as described on the lid of the shipper, as 
follows: 
 
1. Remove the unit from its shipping enclosure. 
 
2. Fill the refrigerator unit completely with liquid nitrogen (do not overfill). 
 
3. Let the unit stand undisturbed while the refrigerant is being absorbed, for 24 hours. 
 
4. Repeat refills three times. 
 
5. Pour out the remaining liquid standing in the central cavity of the refrigerator to 
prevent spillage during shipment. When completely filled, the CP400 should weigh 25 
kg. 
 
When the refrigerator is charged, transfer the material from the liquid nitrogen storage 
tank into the dry shipper as quickly as possible (see GSK Biologicals SOP: 
RD_HCI_009_E for guidance). 
 
Details of the shipment, including number of samples and date of transfer should be sent 
by fax, two days before shipment, to: 
 
GLAXOSMITHKLINE BIOLOGICALS 
Attention Biospecimen Reception 
Clinical Immunology 
R & D Department/Building 44 
Rue de l'Institut, 89 
B-1330 Rixensart - Belgium 
Telephone: 
 
 
 
                                                   E-mail:  
Fax: 
PPD 
PPD
PPD

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Amendment 2 
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Appendix F 
Laboratory Assays 
 
Serology: antibody responses 
 
Blood samples for antibody determination will be collected at indicated timepoints and 
serum will be separated and frozen at -- 20°C. 
 
Antibody level will be determined by evaluating antibody (IgG) responses to p17, p24, 
RT, Nef and F4co, using standard ELISA. The ELISA utilizes antibody and antigen 
interactions to test for the presence of specific antibodies in the serum sample. The 
antigens are chosen from the evaluated vaccine based on what is likely to be an 
immunogenic component. 
 
Partially purified antigen is pre-coated onto a 96-well plate. Serum samples are added to 
the plate followed by a secondary anti-human antibody conjugated with an enzyme. The 
addition of substrate provides a means of detecting the serum antibody that is specific for 
the antigens. Positive control, calibrators are run on each plate in order to assess the 
relative titre of each test sample. Negative controls are also run on each plate to ensure 
specificity. 
 
Cell-mediated immune responses 
Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood cells. 107 
PBMC/vial will be frozen for subsequent CMI analysis. PBMC will be re-suspended in 1 
mL of 90% cold fetal calf serum and 10% DMSO. Cells will then be frozen slowly to -- 
70°C (5°C) and transferred to liquid nitrogen for storage. 
 
Flow cytometry using Intracellular Cytokine Staining (ICS) provides information on the 
frequency of CD4+ and CD8+ T cells responding to the antigen. It provides 
simultaneously information on the frequency of CD4+ 1 CD8+ T-lymphocytes expressing 
molecules involved in immunity such as IFN-, IL-2, TNF-and/or CD40L. Other 
markers may be used for exploratory analysis and further definition of the quality of the 
induced immune response. 
 
PBMCs are stimulated in vitro with pools of peptides covering the sequences of p17, p24, 
RT or Nef antigens for 2 hours; then intracellular block is added (to inhibit cytokine 
secretion) for an additional overnight incubation. The cells will be stained for surface 
markers (e.g. CD4+ or CD8+ for T cells), than fixed and permeabilized, and subsequently 
stained with fluoresent antibodies to detect cytokines. The cells will then be analysed by 
flow cytometry. 

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Appendix G Vaccine supplies, packaging and accountability 
 
1. Vaccine and/or other supplies 
GSK Biologicals will supply the following study vaccines, sufficient number of vials and 
syringes to administer to all subjects as described in the present protocol. 
 
• 
F4co (p24-RT-Nef-p17) antigen in monodose vials 
• 
AS01B adjuvant in monodose vials 
• 
Water for injection in single-dose syringes 
At least an additional 5% of their respective amounts will be supplied for replacement in 
case of breakage, bad storage conditions or any other reason that would make the vaccine 
unusable (i.e. given by mistake to another subject). 
All monodose vials must be accounted for on the form provided. 
Labels for sample identification: 
The investigator will receive labels from GSK Biologicals to identify samples taken from 
each subject at each timepoint. Each label will contain the following information: study 
number, identification number for the subject (e.g. Subject number), sampling timepoint 
(e.g., post vacc 3), timing (e.g., study Month 7). 
 
Other supplies provided by GSK Biologicals: 
In addition to the vaccines, the study documentation and the sample labels, the 
investigator will receive the following supplies: 
 
• 
tubes with screw caps for serum samples, 
• 
racks and cardboard boxes for the tubes of serum. 
The investigator or pharmacist must sign a statement that he/she has received the clinical 
supplies for the study. 
 
It is NOT permitted to use any of the supplies provided by GSK Biologicals for purposes 
other than those specified in the protocol. 
 
2. Vaccine packaging 
The vaccines will be packed in labelled boxes. The box label will contain, as a minimum, 
the following information: study number, treatment number, lot number (or numbers, 
when double-blind), instructions for vaccine administration and any other relevant 
regulatory requirements. 
 
3. Vaccine shipment from GSK Biologicals Rixensart to local country medical 
department, dispatching center or investigational site from local country 
medical department to investigational site 
Upon reception of the shipment,its content, quality and maintenance of the cold chain 
must be checked. 

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Supplies receipt must then be returned to: 
 
Attention of Clinical Trials Supplies Unit 
GSK Biologicals Rixensart 
Fax : 
E-mail: 
In case of any temperature deviation, the official written approval for the use of vaccine 
must be obtained from GSK. 
 
4. Vaccine accountability 
At all times the figures on supplied, used and remaining vaccines should match. At the 
end of the study, it must be possible to reconcile delivery records with those of used and 
unused stocks. An explanation must be given of any discrepancies. 
 
After approval from GSK Biologicals and in accordance with GSK SOP WWD-1102, 
used and unused vaccine vials/syringes/containers should be destroyed at the study site 
using locally approved biosafety procedures and documentation unless otherwise 
described in the protocol. If no adequate biosafety procedures are available at the study 
site, the used and unused vaccine vials/syringes/containers are to be returned to an 
appropriate GSK Biologicals site for destruction, also in accordance with current GSK 
SOP WWD-1102. 
 
5. Transfers of clinical vaccines or products from country medical department or 
dispatch center to study sites or between sites 
Storage temperatures must be maintained during transport and deviations must be 
reported to GSK for guidance. All transfers of clinical vaccines or products must be 
documented using the Clinical Supply Transfer Form. 
 
All packaging and shipment procedures for transfer of clinical vaccines or products must 
follow procedures approved by the sponsor. 
 
Clinical vaccines or products should always be sent by contract courier designated by the 
sponsor, unless otherwise requested by the sponsor. 
PPD
PPD

CONFIDENTIAL 
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Amendment 2 
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Appendix H Detection of intercurrent HIV-1 infection 
 
At screening 
The presence of HIV Ab and Ag will be tested using the Abbott AxSYM HIV Ag1Ab 
ELISA test.  The AxSYM assay allows detection of Abs to HIV-1 group "M" gp41, HIV- 
2 gp36 and HIV group "O" gp41, and detection of the HIV p24 Ag. 
If the result is negative, the subject can be enrolled 
If the result is positive, the ELISA test will be repeated and a Western Blot performed 
using the Innogenetics Line Immunoblot Assay (INNO-LIA). This assay is a blot-assay 
for HIV antibody detection using recombinant proteins and synthetic peptides as 
antigens. The following antigens are applied on the strips: sgp120, gp41, p31, p24, p17, 
sgp105 and gp36 and allow detection of HIV-1, HIV-2 and HIV-1 group "O" infections. . 
 
 
 
At all the other visits 
The same procedure as described for the screening will be followed. 
Subjects with positive or equivalent test results will be referred to the Infectious Diseases 
Clinic. 

CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
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Clara van der Zee 
Appendix  I 
Amendments and Administrative Changes to the Protocol 
 
GlaxoSmithKline  Biologicals 
Clinical Research & Development 
Protocol Amendment Approval 
eTrack study number 
108706 
eTrack abbreviated title 
PRO HIV-005 
EudraCT number 
2006-003796-12 
Protocol Title 
Dose-ranging study to evaluate the safety and 
immunogenicity of GSK Biologicals' HIV vaccine 
732461, adjuvanted or not, when administered as a 2-dose 
schedule to healthy adult HIV seronegative volunteers, 
aged 18 to 40 years. 
Amendment number: 
1 
Amendment date: 
September 24, 2007 
Co-ordinating author: 
PPD 
(Scientific writer, Clinical Operations) 
Rationale/background for changes: 
• 
The third vaccination will be cancelled. A preclinical toxicology study using a 
prime boost combination of F4co / AS01B and a DNA vaccine (GW825780X) 
concluded that potentially treatment-related effects can not be excluded and 
further toxicology studies are required to fully understand the data. The results of 
the new toxicology will only become available in early 2008.  As the primary 
study endpoint of HIV-005 has already been met and subjects will be over a year 
post vaccination by the time the toxicology data is available, it has been decided 
to cancel the third vaccine dose. 
• 
Visit 5 FU has been cancelled as the subjects were attending for safety follow up 
one week post vaccination. As no third vaccination is to take place it was decided 
that it is preferable to subjects not to attend this visit. 
• 
CMI and serology bloods will not be taken at visit 6 although haematology / 
biochemistry and virology bloods will be taken. 
• 
The interim analysis post visit 6 will not be carried out as there is no CMI or 
serology analyses at visit 6. 
• 
The study visit at Month 7 will be postponed to Month 9. 
• 
A new Central Study Coordinator has been appointed. 
Amended text has been included in bold italics in the following section(s): 
Detailed Title: Dose-ranging study to evaluate the safety and immunogenicity of GSK 
Biologicals' HIV vaccine 732461, adjuvanted or not, when administered as a 3 2-dose 

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+32.2.656. 80.44 
 
 
108706 (PRO HIV-005) 
CONFIDENTIAL 
Amendment 2 
, 
 
 
 
 or
 
+32.477.404.713 
+32.474.534.S6S 
PPD 
PPD 
CONFIDENTIAL  
108706 (PRO HIV-005) 
Amendment 2 
schedule to healthy adult HIV seronegative volunteers, aged 18 to 40 years. 
 
Title: A Phase I-II partially-blinded, randomized, dose- ranging study (10-30-90 g) to 
compare the safety and immunogenicity of GSK Biologicals' candidate HIV vaccine 
F4co (p24-RT-Nef-p17), adjuvanted or not with AS01B, administered intramuscularly 
according to a vaccination schedule of 0, 1, 6 months to healthy adult HIV seronegative 
volunteers, aged 18 to 40 years. 
 
Sponsor information: 
3. 
Study Monitor 
GlaxoSmithKline Biologicals 
Phone: 
Fax: 
 
 
, Central Study Coordinator 
4. 
Study Contact for Reporting of a Serious Adverse Event 
Central Study Coordinator 
GlaxoSmithKline Biologicals 
Phone:  
Fax:
 
GSK Biologicals Clinical Safety Physician 
GlaxoSmithKline Biologicals 
Phone:
Fax: 
Mobile phone /or 717 day availability: 
Back-up mobile phone contact: 
 
Synopsis: 
Secondary Objectives 
• 
To evaluate the CD4+ T-cell immune response to the candidate vaccine F4co 
(p24-RT-Nef-p17) with or without AS01B at three different doses (10-30-90 g) 
after two and three vaccinations. 
• 
To evaluate the serological response to the candidate vaccine F4co (p24-RT-Nef- 
p17) with or without AS01B at three different doses (10-30-90 g) after two and 
three vaccinations. 
Study Design 
• 
Vaccination schedule: 3 2 vaccinations administered intramuscularly according to 
a 0, 1, 6 month schedule. 
Primary endpoints 
• 
Haematological and biochemical levels at months 0, 1, 2, 6, 7 9, 12 and at Day 44 
(two weeks after the second vaccination) in all subjects. 
Secondary endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). 
PPD 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

October 8, 2007 
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108706 (PRO HIV-005) 
CONFIDENTIAL 
Amendment 2 
Screening 
Screening 
visit 
Day -56 to -1 
Blood sample 
 
 
CONFIDENTIAL  
108706 (PRO HIV-005) 
Amendment 2 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing at least 2 
cytokines including IL-2 equal or above the cut-off at Months 0, 2, 6, 7, 12 and at 
Day 44 (two weeks after the second vaccination). 
• 
Antibody titers to p17, p24, Nef, RT and F4co as measured by ELISA at Months 0, 
2, 6, 7, 12 and at Day 44 (two weeks after the second vaccination). 
Exploratory endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 12 
and at Day 44 (two weeks after the second vaccination). 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing at least 2 
cytokines (IL-2 and/or TNF-and/or IFN-and/or CD40-L) equal or above the 
cut-off at Months 0, 2, 6, 7, 12 and at Day 44 (two weeks after the second 
vaccination). 
 
Section 2.2 Secondary objectives 
• 
To evaluate the CD4+ T-cell immune response to the candidate vaccine F4co 
(p24-RT-Nef-p17) with or without AS01B at three different doses (10-30-90 g) 
after two and three vaccinations. 
• 
To evaluate the serological response to the candidate vaccine F4co (p24-RT-Nef- 
p17) with or without AS01B at three different doses (10-30-90 g) after two and 
three vaccinations. 
 
Section 3. Study design overview 
Figure 1 Overall study design overview 
F4 (10 µg) + AS01B (N = 50) 
F4 (10 µg) + WFI (N = 10) 
F4 (30 µg) + AS01B (N = 50) 
F4 (30 µg) + WFI (N = 10) 
F4 (90 µg) + AS01B (N = 50) 
F4 (90 µg) + WFI (N = 10) 
 
 
 
 
 
 
Study conclusion 
 
 
Visit 1 
Day 0 
Randomization 
Vaccination 
Blood 
sample 
 
Vis 
Da 
Vaccn 
Blo 
sa 
 
Visit 3 
Day 44 
Blood 
sample 
 
Visit 4 
Day 60 
Blood 
sample 
 
Vis 
Day 
 Vacci 
Blo 
sa 
 
Follow-up 
visit 1 
Day 7* 
 
* For the 12 first vaccinated subjects only at each of the 3 vaccine doses (10, 30 and 90 µg) 
 
 
Figure 2 Staggered design overview 
it 2 
y 30 
i ation 
d 
ple 
Follow-up 
visit 2 
Day 37* 
it 5 
180 
nation 
d 
mple 
Visit 6 
Visit 7 
Day 210 
Day 360 
Day 270 
Blood 
Blood 
sample 
sample 
 Follow-up 
 visit 5   
 Day 187* 

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CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
 
 
 
The same approach will be repeated with each of the three vaccine doses (10, 30 and 
90 g) and for each of the three two vaccinations (see Section 5.6.3). 
Exactly the same methodological approach will be replicated for the third vaccination 
in each dose group (see Section 5.6.3). 
• 
ThreeTwo-vaccination course given at 0, and 1 and 6 months. All vaccinations 
will be administered by the intramuscular route in the deltoid of the non-dominant 
arm. 
• 
Recording of serious adverse events (SAEs) in a prospective manner throughout 
the study period, i.e., the period beginning with the first vaccination and ending 6 
11 months after the third second vaccination. 
• 
Three Two separate analyses will be performed on cleaned data: 
A second analysis will be performed when all data (immunogenicity and 
reactogenicity) up to and including 1 month post-vaccination III are available. 
A third second analysis on the immunogenicity persistence data and SAEs data 
will be performed at the completion of the study (Month 12). 
Section 5.2.1.3 Diary Cards 
Table 2 
Overview of diary cards 

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CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
 
 
 
Type of diary 
card 
Subjects 
Distribution 
Return 
Day 0 - Day 6 
12 first subjects of each dose group 
12 first subjects of each dose group 
12 first subjects of each dose group 
Visit 1 (Day 0) 
Visit 2 (Day 30) 
Visit 5 (Day 180) 
Follow-up Visit 1 (Day 7) 
Follow-up Visit 2 (Day 37) 
Follow-up Visit 5 (Day 187) 
Day 7 - Day 29 
12 first subjects of each dose group 
12 first subjects of each dose group 
12 first subjects of each dose group 
Follow-up Visit 1 (Day 7) 
Follow-up Visit 2 (Day 37) 
Follow-up Visit 5 (Day 187) 
Visit 2 (Day 30) 
Visit 4 (Day 60) 
Visit 6 (Day 210) 
Day 0 - Day 29 
48 other subjects of each dose group 
48 other subjects of each dose group 
48 other subjects of each dose group 
Visit 1 (Day 0) 
Visit 2 (Day 30) 
Visit 5 (Day 180) 
Visit 2 (Day 30) 
Visit 4 (Day 60) 
Visit 6 (Day 210) 
Section 5.1.2.4 Laboratory parameters 
Effects on the haematological and biochemical parameters will be monitored at the 
Screening Visit, Visit 1 (Day 0), Visit 2 (Day 30), Visit 3 (Day 44), Visit 4 (Day 60), 
Visit 5 (Day 180), Visit 6 (Day 210 270) and Visit 7 (Day 360). 
Section 5.2.2 Detection of intercurrent HIV infection 
• 
Laboratory assessment of potential intercurrent HIV-1 infection 
HIV Ag /Ab ELISA testing will be routinely performed at screening, vaccine dose 
1, 1 month post-vaccination III Month 9 and Month 12. 
Section 5.4 Outline of study procedures 
Table 3 List of study procedures 
Visit 
Screenin 
g 
1 
Follo 
w-up 
visit 
11 
2 Follo 
w-up 
visit 
21 
3 
4 
5 
Follow- 
up visit 
51 
6 
7 
Timing (Months) 
Timing (Days) 
Screenin 
g 
-56 to - 
1 
0 
0 
7 
1 
30 
37 
44 
2 
60 
6 
180 
187 
7 9 
210 
270 
12 
360 
Sampling time point 
PRE 
(M0) 
P l 
(M1 
) 
P ll 
(M1. 
5) 
P ll 
(M2) 
P ll 
(M6) 
P lll 
Pll  
(M7) 
(M9) 
P lll Pll 
(M12) 
Vaccination 
l 
ll 
lll 
Examination and Procedure: 
Signed Consent Form 
• 
Signed Addendum to Consent 
Form 
• 
Randomization 
• 
Physical examination and vital 
signs 
• 
• 
• 
• 
• 
Demographic data 
• 
General medical history 
• 
Prevention Counselling 
(pregnancy and HIV) 
• 
• 
• 
• 
Inclusion/exclusion  criteria 
• 
○ 

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Amendment 2 
 
 
Elimination criteria 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
Contraindications 
• 
• 
 •- 
Behavioural risk assessment 
[questionnaire to be filled in by 
the subject and high or low risk 
to be recorded on CRF] 
• 
• 
• 
Pre-vaccination body 
temperature 
• 
• 
 •- 
Distribution of diary card 
○ 
○1 
○ 
○1 
 ○- 
 ○ 1 
Return of diary card 
○1 
○ 
○1 
○ 
 ○ 1 
 ○- 
Transcription of solicited 
symptoms recorded by the 
subjects (Day 0 to Day 6) 
•1 
• 
•1 
• 
 •1 
 •- 
Recording of non-serious 
unsolicited adverse events 
occurring within one month 
post-vaccination by Investigator 
(Day 0 to Day 29) 
•1 
• 
•1 
• 
 •1 
 •- 
Reporting of serious adverse 
events 
• 
• 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
• 
Record any concomitant 
medications 
• 
•1 
• 
•1 
• 
• 
•4 
 •1 
•4 
•4 
Study conclusion 
• 
 •- 
• 

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Blood Sample (ml): 
11 
101 
6.5 
96.5 96.5 
56.5 
61 
11 
69 
Virology(4.5 ml) 
Hep B/C markers: anti HBC Ab, 
HBsAg, 
Anti HCV Ab 
• 
HIV Ag/Abt 
• 
• 
• 
• 
Panel of HlV tests (8 ml)* 
• 
Biochemistry/Haematology 
(6.5 ml) 
• 
• 
• 
• 
• 
• 
• 
• 
Serology (10 ml) 
Anti-p17,-24,-RT,-Nef,  -F4co 
antibodies (ELISA) 
• 
• 
• 
• 
 •  
• 
Cellular-mediated  immunity 
(40 or 80 ml)** 
p17-,24-,RT-,Nef-  Specific 
effector 
T-cells (ICS) 
• 
• 
• 
• 
 •  
• 
Urine Sample: 
Pregnancy test (HCG), if 
applicable 
• 
• 
• 
 •- 
Note: The double-line border following Month 2 and Month 7 indicates the 2 overall interim analyses that will be 
performed on all serology and immunogenicity data obtained up to PII (M2) and PIII (M7). 
•: Is used to indicate a study procedure which requires documentation in the individual eCRF; O is used to indicate a 
study procedure that does not require documentation in the individual eCRF; •1: In the 12 first vaccinated subjects of 
each dose group only; •: Only those SAEs that are considered related to study procedures need to be recorded (see 
Section 8.4); •: To be recorded only if the subject is not a screening failure. . ••4 Recording of concomitant 
medications till 30 days after vaccination. Please refer to Section6.9 for description of 
concomitant/contraindicated medication to be recorded 
t Abbott AxSYM HIV Ag/Ab ELISA assay, which allows detection of Absto HIV-1 group "M" gp41, HIV-2 gp36 and HIV 
group"O" gp41, and detection of the HIV p24 Ag. 
* At the final study visit or following a subject's withdrawal from the study. 
** 80 mL of blood are needed for cellular-mediated immunity when cross-reactivity is determined pre-vaccination (Day 
0), PII (M 1.5) (Day 44) and PII (M2) (Day 60). Otherwise, 40 mL of blood are enough for classical cellular-mediated 
immunity assessment at the other time points. 
Table 4 Intervals between study visits 
lnterval 
length of interval (Days) 
1 (Screening Visit 1) 
2 (Visit 1 Follow-up Visit 1)* 
3 (Visit 1 Visit 2) 
4 (Visit 2 Follow-up Visit 2)* 
5 (Visit 2 Visit 3) 
6 (Visit 2 Visit 4) 
7 (Visit 1 Visit 5) 
8(Visit 5 Follow-up Visit 5)* 
9 (Visit 5 1Visit 6) 
10 (Visit 5 Visit 7) 
1 to 56 (8 weeks) 
7- 8* 
30 - 34 
7 - 8* 
14 2 
30 - 34 
180 14 
7 - 8* 
30 - 34 270 21 
180 14 
* For the 12 first vaccinated subjects only 
Section 5.5.8 Study Visit 5: Third vaccination (Day 180 - Month 6) 
Prior to Vaccination 

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108706 (PRO HIV-005) 
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CONFIDENTIAL  
108706 (PRO HIV-005) 
Amendment 2 
• 
Signed addendum to informed consent form prior to study continuation. 
• 
History-directed physical examination and vital signs. 
 • 
Pre-vaccination assessment of body temperature 
• 
Counselling on avoidance of HIV infection and pregnancy. 
• 
Check of elimination criteria. 
• 
Check of contraindications to vaccination. 
• 
Behavioural risk assessment questionnaire (hard copy) to be filled in by the subject. 
• 
Reporting of any serious adverse events which might have occurred since 
vaccination. The subjects will be instructed to contact the investigator 
immediately should they manifest any signs or symptoms they perceive as 
serious. 
• 
Recording of any contraindicated concomitant medication/treatment/vaccination 
taken since the last visit (see Section 6.9). 
 • 
A urine pregnancy test for females of reproductive potential will be performed. 
• 
Collection of blood (56.5 mL) for biochemistry, haematology, serology and 
cellular-mediated immunity. 
• 
Evaluations and blood draws must be performed prior to vaccination, but it is not 
necessary to have results (except for pregnancy test) prior to the administration of 
the vaccine. 
Vaccination 
 • 
Vaccination: intramuscular administration in the deltoid muscle of the non- 
dominant arm. The vaccinees will be observed closely for at least 30 minutes, with 
appropriate medical treatment readily available in case of a rare anaphylactic 
reaction following the administration of vaccines. 
 • 
Reporting of serious adverse events. The subjects will be instructed to contact the 
investigator immediately should they manifest any signs or symptoms they 
perceive as serious. 
• 
Diary cards will be provided for the subjects to record temperature and any local 
(at the injection site) or general adverse events occurring on the day of vaccination 
and the 6 following days. 
• 
The first 12 vaccinated subjects will be instructed to return their completed Day 0 
to Day 6 diary cards on Day 187 to the investigator. All the other subjects will be 
instructed to return their Day 0 to Day 29 diary cards on Day 210 to the 
investigator. 
 
Section 5.5.9. Follow-up Visit 5 (Day 187; in the first 12 vaccinated subjects only) 
 • 
Check elimination criteria 
 • 
The subjects will return their completed (Day 0 to Day 6) diary cards to the 
investigator, who will transcribe them into the eCRF. 
 • 
Reporting of any unsolicited adverse events which might have occurred since 
vaccination. 
 • 
Reporting of any serious adverse events which might have occurred since 
vaccination. 
 • 
Recording of any concomitant medication/treatment/vaccination taken since the 
last visit (see Section 6.9). 
 • 
Subjects will be distributed Day 7 to Day 29 diary cards and will be instructed to 

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CONFIDENTIAL 
108706 (PRO HIV-005) 
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return them completed on Day 210 to the investigator. 
Section 5.5.10 Study Visit 6 (Day 210 270 - Month 7 9) 
 • 
The subjects will return their completed diary cards (Day 7 to Day 29 diary cards 
for the 12 first vaccinated subjects and Day 0 to Day 29 diary cards for all the other 
subjects) to the investigator, who will transcribe them into the eCRF. 
 • 
The investigator will record any non-serious unsolicited adverse events which 
might have occurred within one month (Day 0 to Day 29) post-vaccination. 
• 
Reporting of serious adverse events which might have occurred since the last visit. 
• 
Recording of any contraindicated concomitant medication/treatment/vaccination 
taken since the last visit (see Section 6.9). 
• 
Collection of blood (61 11 mL) for virology, biochemistry, and haematology, 
serology and cellular-mediated immunity. 
 • 
Study conclusion (for interim analysis). 
Section 5.6.1 Staggered design 
Exactly the same methodological approach will be replicated for the third vaccination in 
each dose group. 
Section 5.6.2 Review of safety data 
Vaccinations are scheduled on Days 0, and 30 and 180 and additional safety 
evaluations 7 days after each vaccination. The following events must occur within the 
specified timeframe to ensure proceeding to the next vaccination and to the next dose as 
per schedule. 
Section 5.6.3 Holding rules 
These holding or stopping rules will be applied to each of the three vaccine doses (10, 
30 and 90 g) and to each of the three two vaccinations. 
Section 5.7.3 Immunological read-outs 
Table 6 Immunological read-outs (timings, markers, numbers of subjects and 
laboratory) 
Blood sampling timepoint 
Marker 
No. 
subjects 
laboratory 
Timing 
Timepoint Visit 
Pre 
Day 0 
1 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post II 
Day 44 
3 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 
Post II 
Day 60 
4 
Anti-p17, -p24, -RT, -Nef, -F4co 
180 
CEVAC, 
antibodies (ELISA) 
Belgium 
p17-,p24-,RT-, Nef-Specific effector T 
180 
*CEVAC, 
cells (ICS) 
Belgium 

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CONFIDENTIAL 
108706 (PRO HIV-005) 
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Post II 
Day 180 
5 
Anti-p17, -p24, -RT, -Nef, -F4co 
antibodies (ELISA) 
p17-,p24-,RT-, Nef-Specific effector T 
cells (ICS) 
180 
180 
CEVAC, 
Belgium 
*CEVAC, 
Belgium 
Post III 
Day 210 
6 
Anti-p17, -p24, -RT, -Nef, -F4co 
antibodies (ELISA) 
p17-,p24-,RT-, Nef-Specific effector T  
cells (ICS) 
180 
180 
CEVAC, 
Belgium 
*CEVAC, 
Belgium 
Post III 
Post ll 
Day 360 
7 
Anti-p17, -p24, -RT, -Nef, -F4co 
antibodies (ELISA) 
p17-,p24-,RT-, Nef-Specific effector T 
cells (ICS) 
180 
180 
CEVAC, 
Belgium 
*CEVAC, 
Belgium 
* Or GSK Biologicals 
Section 8.4 Time period, frequency, and method of dectecting adverse events and 
serious adverse events. 
The standard time period for collecting and recording SAEs will begin at the first receipt 
of vaccine and will end 6 11 months following injection of the last dose of vaccine for 
each subject. See Section 8.7 for instructions for reporting and recording SAEs. 
Section 8.7.2 Completion and transmission of serious adverse events reports to 
GSK 
Study Contact for Reporting SAEs 
, Central Study Coordinator, Clinical R & D 
GlaxoSmithKline Biologicals 
Tel: 
 
Fax: 
 
E-mail address: 
 
 
Back-up Study Contact for Reporting SAEs 
GSK Biologicals Clinical Safety Physician 
Tel: 
 
Fax: 
 or 
 
Mobile phones for 717 day availability: 
 
Back-up mobile phone contact: 
 
 
24/24 hour and 7/7 day availability 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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108706 (PRO HIV-005) 
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Amendment 2 
 
 
 
Section 10.1 Primary endpoints 
CONFIDENTIAL  
108706 (PRO HIV-005) 
Amendment 2 
• 
Haematological and biochemical levels at months 0, 1, 2, 6, 7 9, 12 and at Day 44 
(two weeks after the second vaccination) in all subjects. 
Section 10.2 Secondary endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 
12 and at Day 44 (two weeks after the second vaccination). 
• 
Frequency of p17, p24, Nef and RT-specific CD4+ T cells expressing at least 2 
cytokines including IL-2 equal or above the cut-off at Months 0, 2, 6, 7, 12 and at 
Day 44 (two weeks after the second vaccination). 
• 
Antibody titers to p17, p24, Nef, RT and F4co as measured by ELISA at Months 
0, 2, 6, 7, 12 and at Day 44 (two weeks after the second vaccination). 
 
Section 10.3 Exploratory endpoints 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing IL-2 and/or 
TNF-and/or IFN-and/or CD40-L, as determined by ICS at Months 0, 2, 6, 7, 
12 and at Day 44 (two weeks after the second vaccination). 
• 
Frequency of p17, p24, Nef and RT-specific CD8+ T cells expressing at least 2 
cytokines (IL-2 and/or TNF-and/or IFN-and/or CD40-L) equal or above the 
cut-off at Months 0, 2, 6, 7, 12 and at Day 44 (two weeks after the second 
vaccination). 
 
Section 10.7.2 Analysis of immunogenicity 
For cell-mediated immune response, the following parameters will be tabulated by 
vaccine groups at months 0, 2, 6, 7, 12 and at day 44 (two weeks after the second 
vaccination): 
For CD4+ T-cells expressing IL-2 and another cytokine response, the following 
parameters will be tabulated by vaccine groups at months 0, 2, 6, 7, 12 and at day 44 
(two weeks after the second vaccination) 
For CD8+ T-cells expressing at least 2 cytokines, percentage of responders to each 
antigen (p17, p24, Nef, RT) will be tabulated by vaccine groups at months 0, 2, 6, 7, 12 
and at day 44 (two weeks after the second vaccination). 
For humoral immune response, the following parameters will be tabulated by vaccine 
groups for each antigen (p17, p24, Nef, RT and F4co) at months 0, 2, 6, 7, 12 and at 
day 44 (two weeks after the second vaccination) 
 
Section 10.8 Planned interim analyses 
Nine Six interim analyses are planned for safety evaluation (see Section 5.6). 
These analyses will be performed at the end of the 7-day follow-up period (Days 7, 
and 37 and 187) after each vaccine injection in a subset of 12 subjects and for each 
vaccine dose (10, 30 and 90 g). 
Final analyses will be performed by groups on cleaned data and in three two steps. 
 • 
A second analysis will be performed when all data up to and including month 7 
(immogenicity and safety) will be available. 
A third second analysis will be performed and a clinical report will be written at the 
completion of the study 

October 8, 2007 
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Clara van der Zee 
CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
 
 
 
GlaxoSmithKline  Biologicals 
Clinical Research & Development 
Protocol Amendment Approval 
eTrack study number 
108706 
eTrack abbreviated title 
PRO HIV-005 
EudraCT number 
2006-003796-12 
Protocol Title 
Dose-ranging study to evaluate the safety and 
immunogenicity of GSK Biologicals' HIV vaccine 
732461, adjuvanted or not, when administered as a 2-dose 
schedule to healthy adult HIV seronegative volunteers, 
aged 18 to 40 years. 
Amendment number: 
2 
Amendment date: 
October 08, 2007 
Co-ordinating author: 
PPD 
(Scientific writer, Clinical Operations) 
Rationale/background for changes: 
• 
The Addendum to the Consent Form has to been signed at Visit 6 on Day 270. 
Amended text has been included in bold italics in the following section(s): 
In Table 3 List of study procedures, row 7: 
Visit 
Screening 1 Follow- 
up visit 
11 
2 Follow- 
up visit 
21 
3 
4 
5 Follow- 
up visit 
51 
6 
7 
Timing (Months) 
Timing (Days) 
Screening 
-56 to -1 
0 
0 
7 
1 
30 
37 
44 
2 
60 
6 
180 
187 
7 9 
210 
270 
12 
360 
Sampling time point 
PRE 
(M0) 
P l 
(M1) 
P ll 
(M1.5) 
P ll 
(M2) 
P ll 
(M6) 
P lll 
P ll 
(M7) 
(M9) 
P lll 
P ll (M12) 
Vaccination 
l 
ll 
lll 
Examination and 
Procedure: 
Signed Consent Form 
• 
Signed Addendum to 
Consent Form (Amended 
October 08, 2007) 
 •- 
• 
Randomization 
• 
Physical examination and 
vital signs 
• 
• 
• 
• 
• 
Demographic data 
• 
General medical history 
• 
Prevention Counselling 
(pregnancy and HIV) 
• 
• 
• 
• 

October 8, 2007 
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CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
Inclusion/exclusion  criteria 
• 
○ 
Elimination criteria 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
Contraindications 
• 
• 
 •- 
Behavioural risk assessment 
[questionnaire to be filled in 
by the subject and high or 
low risk to be recorded on 
CRF] 
• 
• 
• 
Pre-vaccination body 
temperature 
• 
• 
 •- 
Distribution of diary card 
○ 
○1 
○ 
○1 
 ○- 
 ○ 1 
Return of diary card 
○1 
○ 
○1 
○ 
 ○ 1 
 ○- 
Transcription of solicited 
symptoms recorded by the 
subjects (Day 0 to Day 6) 
•1 
• 
•1 
• 
 •1 
 •- 
Recording of non-serious 
unsolicited adverse events 
occurring within one month 
post-vaccination by 
Investigator (Day 0 to Day 
29) 
•1 
• 
•1 
• 
 •1 
 •- 
Reporting of serious 
adverse events 
• 
• 
•1 
• 
•1 
• 
• 
• 
 •1 
• 
• 
Record any concomitant 
medications 
• 
•1 
• 
•1 
• 
• 
•4 
 •1 
•4 
•4 
Study conclusion 
• 
 •- 
• 
Blood Sample (ml): 
11 
101 
6.5 
96.5 96.5 56.5 
61 
11 
69 
Virology(4.5 ml) 
Hep B/C markers: anti HBC 
Ab, HBsAg, 
Anti HCV Ab 
• 
HIV Ag/Abt 
• 
• 
• 
• 
Panel of HlV tests (8 ml)* 
• 
Biochemistry/Haematology 
(6.5 ml) 
• 
• 
• 
• 
• 
• 
• 
• 
Serology (10 ml) 
Anti-p17,-24,-RT,-Nef,  -F4co 
antibodies (ELISA) 
• 
• 
• 
• 
 •- 
• 
Cellular-mediated 
immunity 
(40 or 80 ml)** 
p17-,24-,RT-,Nef-  Specific 
effector 
T-cells (ICS) 
• 
• 
• 
• 
 •- 
• 
Urine Sample: 
Pregnancy test (HCG), if 
applicable 
• 
• 
• 
 •- 

October 8, 2007 
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CONFIDENTIAL 
108706 (PRO HIV-005) 
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Note: The double-line border following Month 2 and Month 7 indicates the 2 overall interim analyses that will be 
performed on all serology and immunogenicity data obtained up to PII (M2) and PIII (M7). 
•: Is used to indicate a study procedure which requires documentation in the individual eCRF; O is used to indicate a 
study procedure that does not require documentation in the individual eCRF; •1: In the 12 first vaccinated subjects of 
each dose group only; •: Only those SAEs that are considered related to study procedures need to be recorded (see 
Section 8.4); •: To be recorded only if the subject is not a screening failure. •4 Recording of concomitant 
medications till 30 days after vaccination. Please refer to Section 6.9 for description of 
concomitant/contraindicated medication to be recorded. 
t Abbott AxSYM HIV Ag/Ab ELISA assay, which allows detection of Absto HIV-1 group "M" gp41, HIV-2 gp36 and HIV 
group "O" gp41, and detection of the HIV p24 Ag. 
* At the final study visit or following a subject's withdrawal from the study. 
** 80 mL of blood are needed for cellular-mediated immunity when cross-reactivity is determined pre-vaccination (Day 
0), PII (M 1.5) (Day 44) and PII (M2) (Day 60). Otherwise, 40 mL of blood are enough for classical cellular-mediated 
immunity assessment at the other time points. 
 
In section 5.5.8: 
• 
Signed addendum  to  informed  consent form prior to study continuation. 
In section 5.5.10: 
• Signed addendum to informed consent form prior to study continuation. 

October 8, 2007 
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CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
 
 
 
GlaxoSmithKline  Biologicals 
Clinical Research & Development 
Protocol Amendment Approval 
eTrack study number 
108706 
eTrack abbreviated title 
PRO HIV-005 
EudraCT number 
2006-003796-12 
Protocol Title 
Dose-ranging study to evaluate the safety and 
immunogenicity of GSK Biologicals’ HIV vaccine 
732461, adjuvanted or not, when administered as a 2-dose 
schedule to healthy adult HIV seronegative volunteers, 
aged 18 to 40 years. 
Amendment number: 
Amendment 2 
Amendment date: 
October 08, 2007 
Approved by: 
Lead Clinical Development Manager 
 
Lisa Mc Nally, MD 
dd-mm-yyyy 
 
For internal use only 
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October 8, 2007 
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CONFIDENTIAL 
108706 (PRO HIV-005) 
Amendment 2 
 
 
 
 
 
GlaxoSmithKline  Biologicals 
Clinical Research & Development 
Protocol Amendment Approval 
eTrack study number 
108706 
eTrack abbreviated title 
PRO HIV-005 
EudraCT number 
2006-003796-12 
Protocol Title 
Dose-ranging study to evaluate the safety and 
immunogenicity of GSK Biologicals’ HIV vaccine 
732461, adjuvanted or not, when administered as a 2-dose 
schedule to healthy adult HIV seronegative volunteers, 
aged 18 to 40 years. 
Amendment number: 
Amendment 2 
Amendment date: 
October 08, 2007 
Agreed by: 
Investigator: 
Prof. Dr. Geert Leroux-Roels 
Investigator signature: 
Date: 
 
For internal use only 
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