Introduction
 
In December 2004, 35.9-44.3 million individuals were currently living with HIV/AIDS. In the same year, 2.8-3.5 million had reportedly died with a further 4.3-6.4 million new infections (UNAIDS). HIV penetrates marginalized population groups such as women who sell sex, IVDUs and homosexual men. Most are likely to exacerbate viral spread and are furthest from available support.
 

 
Scope
 
In depth overview and case record of the main approaches to HIV vaccine research and development
 
Discussion of key challenges within HIV virology and current understanding of human immunology that have limited current progress
 
In depth analysis of clinical, societal and political factors and how they affect HIV vaccine profile and its subsequent adoption
 
Comment on quantitative potential in each population target group across major Western markets
 
Highlights
 
Despite the success of antiretroviral (HAART) therapy in reducing AIDS related mortality in the developed world, it is becoming clear that to achieve the same impact in poorer countries an additional healthcare intervention such as vaccination will be necessary.
 

 
Early monomeric recombinant subunit strategies, whilst optimistic have helped garner research momentum and public awareness as well as providing useful lessons for later generation approaches using live recombinant vectors.
 

 
Shifting expectations of vaccination, the identification of appropriate trial populations and ethical considerations must be addressed throughout the research, testing and eventual launch process to ensure optimal uptake.
 

 
Reasons to Purchase
 
Understand the strengths and weaknesses associated with differing HIV vaccination strategies
 
Understand critical factors affecting feasibility and logistics of conducted human clinical trials for HIV vaccines
 
Assess relative importance of HIV vaccine profile components and how they affect future adoption
 

TABLE OF CONTENTS
 
CHAPTER 1 EXECUTIVE SUMMARY 3
 
Scope of the analysis 3
 
Datamonitor insight into the HIV vaccines market 4
 
Despite the success of antiretroviral (HAART) therapy in reducing HIV/AIDS related mortality in the developed world; it is becoming clear that a similar impact is not achievable in the developing world where disease burden is highest. The historical success of vaccination as a tool to provide healthcare benefit ‘en masse’ therefore continues to spur the development of a safe and effective HIV vaccine 4
 
Early monomeric recombinant subunit strategies, whilst optimistic have helped garner research momentum, raise public awareness and provide useful lessons for later generation candidates. Whilst approaches such as DNA, live vector and pseudovirion vaccines are providing some hope, there is now a shift towards combinations to best target separate immune responses and different HIV subtypes 7
 
With each increasing compromise to the concept of an ‘ideal HIV vaccine’ it is clear that additional non-clinical challenges present themselves. With attributes such as ‘partial efficacy’ and ‘limited protection’ being espoused as more realistic goals, deciding who would most benefit from a suboptimal vaccine requires strong judgment and skillful implementation; 11
 
The success of HIV vaccines is dependent on cost, target population and governmental support for immunization. This uncertainty, combined with economic and political considerations, is limiting commercial investment in future research. Clarity and support from supra-national organizations and governments on these issues, especially tiered pricing, must be provided. 13
 
Summary 16
 
CHAPTER 2 HIV VACCINES: AN INTRODUCTION 24
 
Background 24
 
The HIV virus: genetic variability creates a complex target 25
 
Superinfection 26
 
Which immune response to target? 27
 
Will HIV vaccination be effective? 27
 
A predictive animal model? 28
 
Non-clinical issues also exert an influence 31
 
Current approaches to HIV vaccines 31
 
Recombinant subunit vaccines 32
 
Protein vaccines 33
 
Peptide-based vaccines 36
 
Pseudovirion/virus-like particle vaccines 38
 
Prime-boost vaccines 38
 
Live vector vaccines 39
 
Pox viruses 40
 
Adenovirus 41
 
Rabies and other viruses 41
 
Live attenuated vaccines 42
 
DNA-based vaccines 43
 
Inactivated/whole killed HIV vaccines 44
 
Summary of approaches currently being investigated 46
 
Key stakeholders 47
 
The International AIDS Vaccine Initiative (IAVI) 47
 
National Institute of Allergy and Infectious Diseases (NIAID) 48
 
European Vaccine Effort against HIV/AIDS 49
 
HIV Vaccine Trials Network (HVTN) 50
 
South African AIDS Vaccine Initiative (SAAVI) 50
 
The Global HIV Vaccine Enterprise 51
 
CHAPTER 3 DEVELOPMENT AND PROGRESS 53
 
Timeline of the development of HIV vaccines 53
 
The need for global cooperation 54
 
The pipeline – an overview 55
 
AIDSVAX 59
 
AIDSVAX B/B 60
 
AIDSVAX B/E 61
 
ALVAC 63
 
vCP125 63
 
vCP205 64
 
vCP300 66
 
vCP1433 66
 
vCP1521 67
 
St. Jude Children’s Research Hospital 69
 
PolyEnv1 69
 
EnvPro 70
 
Current status 70
 
Merck & Co. 71
 
MRKAd5 HIV-1 gag 71
 
MRKAd5 HIV-1 trivalent 73
 
HIV-1 gag DNA vaccine 74
 
Future prospects 75
 
Partial efficacy 75
 
Protection for all? 77
 
Protection against infection or disease? 78
 
Social impact of a partially effective vaccine 79
 
CHAPTER 4 KEY CHALLENGES AND ISSUES 81
 
Ethical considerations 81
 
Which subtype to target? 82
 
Protection of the individual throughout the trial 83
 
Social, psychological and emotional harm 83
 
Treatment and care for those who become infected in the trial 84
 
Risk behavior – should it be prevented? 85
 
Societal considerations 86
 
Clinical trial considerations 87
 
Trial population – HIV-infected or negative? 88
 
Trial location – developed or developing world? 89
 
Trial size and duration 91
 
Attitudes to vaccination 93
 
Target population 94
 
Moral issues 98
 
Mandatory or voluntary? 99
 
Payment 102
 
Economic and financial considerations 104
 
Current investment in HIV vaccine development 107
 
Public versus private investment 107
 
One single goal but many different approaches 109
 
Political considerations 113
 
Legal barriers 115
 
Regulatory issues 116
 
Tiered prices 116
 
Intellectual property 118
 
CHAPTER 5 COMMERCIAL IMPLICATIONS OF SUCCESS 120
 
An ideal HIV vaccine? 120
 
Pricing and reimbursement considerations 122
 
Implications for antiretroviral therapy 125
 
Epidemiological overview 127
 
CHAPTER 6 OPINION LEADER TRANSCRIPTS 131
 
US opinion leader 131
 
Section 1 – Vaccine technologies 131
 
Section 2 – The current pipeline 137
 
Section 3 –Obstacles to the development of an HIV vaccine 138
 
Section 4 –An ideal HIV vaccine 140
 
Section 5 – Trial considerations 141
 
Section 6 – Target population and immunization schedule 142
 
Section 7 – Compliance and patient attitudes 143
 
Section 8 – Therapeutic vaccines 144
 
French opinion leader 146
 
Section 1 – Vaccine technologies 146
 
Section 2 – The current pipeline 149
 
Section 3 –Obstacles to the development of an HIV vaccine 151
 
Section 4 –An ideal HIV vaccine 153
 
Section 5 – Trial considerations 154
 
Section 6 – Target population and immunization schedule 155
 
Section 7 – Compliance and patient attitudes 157
 
Section 8 – Therapeutic vaccines 157
 
German opinion leader 159
 
Section 1 – Vaccine technologies 159
 
Section 2 – The current pipeline 162
 
Section 3 –Obstacles to the development of an HIV vaccine 164
 
Section 4 –An ideal HIV vaccine 166
 
Section 5 – Trial considerations 167
 
Section 6 – Target population and immunization schedule 168
 
Section 7 – Compliance and patient attitudes 169
 
Section 8 – Therapeutic vaccines 170
 
APPENDIX A ADDITIONAL DATA 172
 
APPENDIX B GLOSSARY AND ASSUMPTIONS 179
 
Glossary 179
 
Assumptions 180
 
APPENDIX C BIBLIOGRAPHY 181
 
Journal & news articles 181
 
Other articles and publications 190
 
Other sources 192
 
Websites 192
 
Disclaimer 194