HIV VACCINE. Punnee Pitisuttithum Donald P. Francis Jose Esparza Prasert Thongcharoen. Editors RESEARCH AND DEVELOPMENT IN THAILAND

Transcription

1 HIV VACCINE RESEARCH AND DEVELOPMENT IN THAILAND Punnee Pitisuttithum Donald P. Francis Jose Esparza Prasert Thongcharoen Editors

2

3 HIV Vaccine Research & Development in Thailand First published January, 2006; quantity 2,000 Copies Owner: Faculty of Tropical Medicine, Mahidol University 420/6 Rajchavithi Road, Bangkok 10400, Thailand Tel , Fax Designed by Commercial Publishing Amarin Printing and Publishing Public Co.,th Editor in Chief Arunee Burusratanapant, Chief Photoghapher Ekapong Sriprasert Photoghapher kong Pahuruk, Teerayuth Jansook, Art Director Saroach Kuphachaka Graplic Designer Suthep Veateekul, Manapan Boonprasert, Pimonrat Patanapeechai, Thanawan Comsawad, Secretary-Traffic Benjamas Pensasitorn, Account Co-ordinator Nalin Nateewathana 65/16 Chaiyaphruk Rd., Taling-Chan, Bangkok 10170, Thailand. Tel Ext.4174 Fax Printed by Business Amarin Printing and Publishing Public Co.,th 65/16 Chaiyaphruk Rd., Taling-Chan, Bangkok 10170, Thailand. Tel Fax Homepage HIV Vaccine Research & Development in Thailand ISBN First printing. Copyright 2006 by Faculty of Tropical Medicine, Mahidol University. All rights reserved. This book may be reproduced in its entirely or incomplete articles for free distribution with written permission from Faculty of Tropical Medicine, Mahidol University. The full text of this book will be available on CD in the future. Copies of this book or CD can be ordered from: Clinical Infectious Diseases Research Unit, Faculty of Tropical Medicine, Mahidol University 420/6 Rajchavithi Road, Bangkok 10400, Thailand. Tel: , Fax: This book is funded by a Research Grant from the Faculty of Tropical Medicine, Mahidol University

4

5 ç T his book is dedicated to all participants, staffs and communities around the world that are contributing to the global effort to develop a safe and effective HIV vaccine.é

6 Foreword The first case of HIV/AIDS was diagnosed in Thailand in By the late 1980s, Thailand was in the throes of an HIV epidemic. HIV/AIDS was an emerging threat to our country and our people, one that no conventional defense measures had prepared our society for. I assumed leadership of Thailand in 1991 at a time when HIV was rampant throughout the country. It was predicted that over the next 20 years, up to 10 per cent of Thais would die from AIDS. We recognized at that time that only government and political leadership at the highest level could make the crucial difference in fighting HIV/AIDS on a national scale. A broad-based programme of prevention, treatment and care was launched involving all sectors of Thai society, including civil society, the private sector and people living with HIV/AIDS. Thailand became the first developing country in the Asia-Pacific region to recognize the severity of AIDS, place the issue high on the national agenda and pioneer a national HIV/AIDS programme with significant national resources. As a result, Thailand was able to successfully reverse a serious HIV/AIDS epidemic in the 1990s. Thailandûs past success may in part have contributed to the current mood of complacency. Current prevention efforts do not fully address the new realities of a shifting epidemic, which has manifested new patterns of spread through mainstream sexual relations, and among young people and men who have sex with men. Unless we renew our commitment to fighting HIV/AIDS, the epidemic may rebound. New strategies and systems are now urgently needed. One significant area of work has been the pursuit of a vaccine to prevent HIV infection, which is the subject of this book. It is my hope that this book can contribute to global efforts to develop a safe and effective HIV vaccine to protect all societies from this deadly disease. Thailandûs people have been deeply affected by HIV and want to see an end to the epidemic. Experts in Thailand have joined forces with colleagues from other countries to advance work in the field of HIV vaccines. And the people of Thailand have also joined these efforts through volunteering for vaccine studies. This book represents over a decade of intensive work by hundreds of people. By sharing their varied experiences, the authors of this book are contributing to a notable cause, namely to develop an effective vaccine xi

7 to combat HIV/AIDS. The process of learning is one that takes into account past lessons and builds on them to ensure a better future for all, This book is intended to provide inspiration and knowledge to those working in the field to promote further advancement to address the HIV/AIDS epidemic. It is my hope we will one day see an end to this formidable epidemic. Anand Panyarachun Former Prime Minister of Thailand (March 2,1991-October 1,1992) xii

8 Foreword In the field of vaccines, coalitions matter. Dr. Bill Foege, for many the dean of Public health, believes that, çleadership in health no longer goes with title. It goes to the person who can assemble a coalition.é This book is about the scientists, health care workers, patients, community leaders, and advocates who united to advance the field of HIV vaccine development in Thailand. They took risks professional and individual and so we owe them gratitude and respect. All of us who read this book will learn from their efforts, and in the process gather renewed energy to overcome the many obstacles that lay ahead. Thailand, its scientists and its people, have played such an important role in advancing HIV vaccine development and evaluation. Few vaccines will be as important for world health as an HIV vaccine the only long-term hope for bringing the global AIDS pandemic to an end. Though the path to discovery will not be easy, and disappointments will out number successes, we are confident that by working together we will find a safe, effective, and affordable vaccine against HIV. Helene D. Gayle M.D, M.P.H Director, HIV, TB & Reproductive Health, Bill and Melinda Gates Foundation. Co-Chair, Coordinating Committee of the Global HIV Vaccine Enterprise President, International AIDS Society xiii

9 Foreword A university is an institute for higher learning. Teaching and research are its two core functions. They both contribute to the universal pool of knowledge that then becomes patrimony of humankind. But this work should also benefit and contribute to the advancement of the community and society where the university exists. As important as these goals are, it is sometimes hard to measure, in a palpable sense, the outcomes of such lofty functions. Other times it is easy to measure. This book is a case in point where university researchers have united with vaccine developers, other government institutions and community volunteers to produce real, practical outcomes. In the end, these efforts, and more like them, will hopefully produce a vaccine that will eliminate the misery and harm caused by HIV/AIDS. For the past 12 years Mahidol University has joined hand in hand with other institutions within Thailand, especially Chulalongkorn University, Chiang Mai University the Royal Thai Army,and Ministry of Public Health, as well as with many international collaborators, to advance the HIV vaccine research forward and that effort is detailed in this book. An important lesson, related to the essence of what a university should be, is that the experiences obtained in different areas of research, sooner or latter would find applications in apparently unrelated areas of emerging interest. The previous work of our dedicated faculty members in the areas of experimental vaccines against dengue, diarrheal diseases, and malaria, just to mention a few, provided valuable experiences that facilitated the rapid development and implementation of a strong and high quality HIV vaccine program in Thailand. And I am also confident that the experiences described in this book will not only inspire and stimulate new generations of scientists working on HIV/AIDS research, but also those working or planning to work in other important areas of scientific and public health interest for Thailand and its neighboring countries. As the generations of new researchers emerge from the training of these outstanding stalwarts, we can be assured of a continuing legacy of outstanding vaccine research. xiiii

10 Thailand, with its strong higher learning institutions and its committed government organizations, will continue to be a world leader in vaccine research and development. It is doing what it should do. And it will continue to do it well. Prof.Pornchai Matangkasombut President of Mahidol University xiiiii

11 Contributors Michael W. Benenson, M.D., M.P.H, Field Operation, Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) U.S. component, Bangkok, Thailand COL Deborah Birx, M.D. Director, US Military HIV Research Program, Rockville, Maryland, USA Jotika Boon-Long, Ph.D. Mycology Section, Division of Clinical Pathology, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand LTC Arthur E. Brown, M.D., M.P.H. Product Manager, The U.S. Army Medical Material Development Activity (USAMMDA), Maryland, USA Vichai Chokevivat, M.D., M.P.H. Director-General of Department of Development of Thai Traditional Medicine and Alternative Medicine, Ministry of Public Health, Nonthaburi, Thailand Kachit Choopanya, M.D., M.P.H., M.P.H & T.M. Principal Investigator, Bangkok Tenofovir Study Group (BTSG), Bangkok Metropolitan Administration (BMA), Bangkok, Thailand MG Cheodchai Chuenchitra, Ph.D. Former Head of Department of Pathology, Armed Forces Research Institute of Medical Sciences (AFRIMS) Thai component, Bangkok, Thailand COL Thippawan Chuenchitra, Ph.D. Head of Department of Microbiology, Armed Forces Research Institute of Medical Sciences (AFRIMS) Thai component, Bangkok, Thailand COL Chirapa Eamsila, M.S. Medical Research Scientist, Armed Forces Research Institute of Medical Sciences (AFRIMS) Thai component, Bangkok, Thailand

12 Jose Esparza, M.D., Ph.D. Senior Advisor on HIV Vaccine, Bill & Melinda Gates Foundation, Seattle, Washington, USA CONTRIBUTORS Donald P. Francis, M.D, D.Sc. Executive Director, Global Solutions for Infectious Diseases, Brisbane, California, USA Helene D. Gayle, M.D., M.P.H Director, HIV, TB & Reproductive Health, Bill & Melinda Gates Foundation; Co-chair, Coordinating Committee of The Global HIV Vaccine Enterprise and President, International AIDS Society Mitsuo Honda, M.D., Ph.D. Head, Vaccine Research and Development Group, AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan Chirasak Khamboonruang, M.D., Ph.D. Consultant, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand LTC Jerome H. Kim, M.D., Ph.D. Chief of Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand Dwip Kitayaporn, M.D., Dr.P.H. Professor, Bumrungrad International Hospital, Bangkok, Thailand Prayura Kunasol, M.D. Consultant, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand Timothy D. Mastro, M.D., F.A.C.P., D.T.M. & H. Acting Director, Global AIDS Program, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, USA Bruce R. Merrell, B.S. Site Manager, Henry M. Jackson Foundation, Seattle, Washington, USA Sricharoen Migasena, M.D., Ph.D., D.T.M. & H., F.R.C.P.T

13 Professor Emeritus, Former Director, Vaccine Trial Center, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Patricia A. Morgan, M.S., P.A. Clinical Research Associate Manager, Henry M. Jackson Foundation, Seattle, Washington, USA COL Sorachai Nitayaphan, M.D., Ph.D. Associate Director, Armed Forces Research Institute of Medical Sciences (AFRIMS) Thai component, Bangkok, Thailand Saladin Osmanov, M.D. Acting Coordinator WHO-UNAIDS HIV Vaccine Initiative, World Health Organization, Geneva, Switzerland Praphan Phanuphak, M.D., Ph.D. Professor, Director, The Thai Red Cross AIDS Research Center and the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Wiput Phoolcharoen, M.D., M.P.H. Former Director, Health System Research Institute, Ministry of Public Health, Nonthaburi, Thailand Punnee Pitisuttithum, M.B.B.S, D.T.M. & H., F.R.C.P.T Professor, Chief, Clinical Infectious Disease Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Duanthanorm Promkhatkaew, Ph.D. Principal Medical Scientist 9, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Supachai Rerks-Ngarm, M.D. Principal Investigator, The Prime Boost HIV Vaccine Phase III Trial. Medical Doctor 10 in Preventive Medicine, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand

14 Nina Russell MD, Senior Program Officer,Bill & Melinda Gates Foundation, Seattle, Washington, USA CONTRIBUTORS Pathom Sawanpanyalert, M.D., Dr.P.H. Director, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Pratap Singhasivanon, M.B.B.S., D.T.M.&H., M.P.H., Dr.P.H. (Epidemiology) Dean, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Mark S. de Souza, M.P.H., Ph.D. Laboratory Director, USAMC-Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand Vinai Suriyanon, M.D. Assistant Professor, The Research Institute for Health Sciences (RIHES), Chiang Mai University, Chiangmai, Thailand Ruengpung Sutthent, M.D., Ph.D. Professor, Head of Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Nusara Thaitawat, B.A., M.A. Director, Capitalize Communications and Community Engagement, The PrimeBoost HIV Vaccine Phase III Trial, Ministry of Public Health, Nonthaburi, Thailand Prasert Thongcharoen, M.D. Professor Emeritus, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Suphak Vanichseni, M.D., M.P.H. Clinic Coordinationship, Bangkok Tenofovir Study Group (BTSG), Bangkok Metropolitan Administration (BMA), Bangkok, Thailand

15 Paijit Warachit, M.D., Ph.D. Director-General of Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Chantapong Wasi, M.D. Associate Professor, Division of Virology, Department of Microbiology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand

16 Acknowledgment This book was made possible by the dedication and effort of many people, first and foremost to those who wrote the articles. The editors would like to give special thanks to Professor Pornchai Matangkasombut, President of Mahidol University, Associate Professor Pratap Singhasivanon, Dean of the Faculty of Tropical Medicine, Mahidol University and Dr. Vichai Chokevivat, Director, Department of Development of Thai Traditional Medicine and Alternative Medicine, Ministry of Public Health for their continued support. Appreciation is also due to Dr. Jeffrey Ray Johns, Director pharmaceutical Science Undergraduate English Program, Coordinator MSc. Health Product Management, the Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University for help in the preliminary editing of some of the Thai authors articles. Special thanks is due to Associate Professor Chayan Picheansoontorn, Head of the Department Pharmaceutical Botany and Pharmacognosy, Faculty of Pharmaceutical Sciences, Khon Kaen University for a great help with the editing process. Finally, we thank Associate Professor Varunee Desakorn, Dr.Aneley Getahuntekle, Sawanya Lekhachinnabut and Nunthiya Kosoldilokkul, Faculty of Tropical Medicine for their assistance in coordinating the publishing of this book. In preparing this volume, as with all of its projects, the Vaccine Trial Centre has relied extensively on the support and encouragement of the Faculty of Tropical Medicine, Mahidol University. We gratefully thank to our staffs and volunteers. Their unending support has contributed greatly to the knowledge of HIV vaccine science.

17 Contents xi xv Foreword Introduction Punnee Pitisuttithum, Donald P. Francis, José Esparza Prasert Thongcharoen Chapter 1 : Setting the stage 3 The Challenge of Developing an HIV Vaccine José Esparza, Nina Russell and Helene Gayle Chapter 2 : The AIDS Epidemic in Thailand 31 Molecular Epidemiology of HIV in Thailand Chantapong Wasi, Ruengpung Sutthent and Saladin Osmanov 53 The Thai Response to the HIV/AIDS Epidemic Wiput Phoolcharoen Chapter 3 : HIV Vaccine Research in Thailand: National Perspective 83 Overview of HIV Vaccine Research in Thailand Punnee Pitisuttithum 95 The Thai National Plan on HIV Vaccine Research and Development Supachai Rerks-Ngam, Chirasak Khamboonruang, Prayura Kunasol and Prasert Thongcharoen 103 National Ethical Review Board Framework Vichai Chokevivat Chapter 4 : Phase I/II HIV Vaccine Trials in Thailand 119 The First HIV Vaccine Trial in Thailand Praphan Phanuphak 131 The Vaccine Trial Center, Faculty of Tropical Medicine, Mahidol University Punnee Pitisuttithum, Sricharoen Migasena and Pratap Singhasivanon 153 The Armed Forces Research Institute of Medical Sciences (AFRIMS): Role in HIV Vaccine Development Partricia A. Morgan, Mark S. de Souza, Thippawan

18 CONTENTS Chuenchitra, Chirapa Eamsila, Bruce R. Merrell, Cheodchai Chuenchitra and Sorachai Nitayaphan 167 The Research Institute for Health Sciences (RIHES), Chiang Mai University, Thailand Vinai Suriyanon Chapter 5 : International Collaborative Efforts 181 Thai and US Military HIV Research Program Arthur E. Brown, Deborah Birx and Jerome H. Kim 195 The HIV Netherlands-Australia-Thailand Research Collaboration (HIV-NAT) Praphan Phanuphak 209 Collaboration between Thailand and Japan on Research and Development of an HIV Vaccine Paijit Warachit, Pathom Sawanpanyalert, Duanthanorm Promkhatkaew, Jotika Boon-Long and Mitsuo Honda Chapter 6 : Developing Cohorts for Phase III Trials of Candidate HIV Vaccines 221 Chiang Mai Community Cohort Chirasak Khamboonruang 241 The Bangkok Metropolitan Administration (BMA) Cohort of Injecting Drug Users (IDUs) Suphak Vanichseni, Dwip Kitayaporn and Timothy D. Mastro 251 Community Cohorts in Rayong and Chon Buri Michael W. Benenson Chapter 7 : Conducting Phase III Trials of Candidate HIV Vaccines 265 Challenges in Performing Phase III Trials of HIV Candidate Vaccines Donald P. Francis 275 Phase III Efficacy Trial of Bivalent B/E rgp120 HIV Vaccine (AIDSVAX B/E) in Bangkok Punnee Pitisuttithum, Suphak Vanichseni, Dwip Kitayaporn and Kachit Choopanya

19 293 The Rayong-Chonburi Community Phase III HIV Vaccine Trial Supachai Rerks-Ngam, Punnee Pitisuttithum, Dwip Kitayaporn, Chirasak Khamboonruang, Sorachai Nitayaphan, Arthur E. Brown, Deborah Birx, Jerome H. Kim and Prayura Kunasol 307 Data Management for HIV Vaccine Efficacy Trials-Infrastructure Strengthening for Clinical Research in Thailand Dwip Kitayaporn 315 From çguinea Pigsé to çguinea pigs:é Community Awareness and Response to AIDS Vaccine Research and Development in Thailand Nusara Thaitawat Chapter 8 : Epilogue 329 Projection on HIV Vaccine Research in Thailand in the Next Decade Praphan Phanuphak 327 Lessons Learnt Punnee Pitisuttithum, Donald P. Francis, 344 Index Jose Esparza, Prasert Thongcharoen 350 Biographies of Editors

20 List of Abbreviations Abbreviations Term ACCESS The AIDS Access Foundation ACTG The AIDS Clinical Trial Group AE Adverse events AFAO The Australian Federation of AIDS Organization AFRIMS Armed Forces Research Institute of Medical Sciences AIDS Acquired Immunodeficiency Syndromes ASO AIDS Service Organization ATC Anonymous HIV Testing Clinic BVEG The Bangkok Vaccine Evaluation Group CAB Community Advisory Boards CAR The Center for AIDS Rights CAP College of American Pathologist CBO Community-Base Organization CDC 1. Centers for Disease Control and Prevention, U.S.A. 2. Department of Communicable Disease Control, MOPH, Thailand CHAVI Center for HIV/AIDS Vaccine Immunology, U.S National Institutes of Health CIR Center for Immunization Research CRC 1. Clinical Research Coordination 2. Community Relation Club CRF Case Report Form CSIRO The Commonwealth Scientific and Industrial Research Organization CSW(s) Commercial Sex Worker(s) DAIDS Division of AIDS, Nation Institute of Health, U.S.A. DM Data manager DMC Data Management Center DMSC Department of Medical Sciences, MOPH,Thailand DOT Directly Observed Therapy-short course DSMB Data Safety Monitoring Board EC Ethics Committees GCP Good Clinical Practice GCLP Good Clinical Laboratory Practice GLP Good Laboratory Practice GMP Good Manufacturing Practice

21 GPA Global Programme on AIDS HIV Human Immunodeficiency Virus HIV-NAT The HIV Netherlands-Australia-Thailand Research Collaboration HIVNET HIV Network for Prevention Trials HMJF Henry M. Jackson Foundation HVDDT The HIV Vaccine Design and Development Team IATEC International AIDS Therapy Evaluation Center IBC Institutional Biosafety Committee ICH International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. IDU(s) Injecting or injection drug user(s) IND Investigation New Drug IRB Institutional Review Boards JCRC Joint Clinical Research Center LPA Lymphoproliferation assay MHLW Ministry of Health, Labour and Welfare, Japan MOPH Ministry of Public Health, Thailand MSM Men who have sex with men MVA Modified Vaccina Ankara Nab Neutralizing antibody NAC National AIDS Committee NCHER The National Center in HIV Epidemiology and Clinical Research NESDB The National Economic and Social Development Board NGO Non-govermental Organization NHRBC National HIV Repository and Bioinformatic Center, Thailand NIH National Institute of Health, U.S.A. NIID The National Institute of Infectious Disease, Japan PAVE Preparation for AIDS Vaccine Evaluation Pfu Plaque forming units PI Principal Investigator PIE Participation Impact Events PND Principal Neutralizing Determinant PWHA People with HIV infection and AIDS QA Quality Assurance QC Quality Control R&D Research and Development RIHES The Research Institute for Health Sciences RIHES HVTU The Research Institute for Health Sciences-HIV Vaccine Trial Unit

22 LIST OF ABBREVIATIONS ROD RTAMC RTG SAE SOP(s) SHIV SIV STA STD TAVEG TBCA TRC-ARC TUC UBI UNAIDS USAMC VRC VSI WHO WRAIR A record of discussion Royal Thai Army Medical Component Royal Thai Government Serious adverse event Standard operating procedure(s) Simian-human immunodeficiency virus Simian immunodeficiency virus The Science and Technology Agency of Japan Sexually Transmitted Disease Thai AIDS Vaccine Evaluation Group Thai Business Coalition on AIDS Thai Red Cross AIDS research Center Thailand MOPH-US CDC Collaboration United Biomedical, Inc. The Joint United Nations Program on AIDS The US Army Medical Component 1. Vaccine Research Center, U.S National Institutes of Health 2. Volunteer Relation Club, The Vaccine Trial Centre Vaccine Senior Investigator The World Health Organization The Walter Reed Army Institute of Research

23 Introduction Human Immunodeficiency virus, type 1 (HIV-1) poses many challenges to modern societies that attempt to deal with its onslaught. Vaccine development is certainly one of these challenges. Seldom if ever in the history of the world have the worldsû people been confronted with tens of thousands of people being infected every day with a virus that has a nearly 100% fatality rate. Despite some progress having been made in both preventing HIV infection through behavioral change programs and in treating infections with anti-retroviral and anti-opportunistic drugs, a safe and effective vaccine to prevent all infections is the only tool that has the potential of stopping the onslaught of HIV. Our newly acquired knowledge and technical tools give us immense potential powers to combat infectious diseases. With todayûs immense knowledge of virology and immunology, and our recently developed technical powers to develop viral vaccines, a vaccine for HIV should be possible. No doubt, the challenges that HIV poses are large, but with a concerted effort, we are optimistic that a vaccine is possible. But the path to an HIV vaccine will be a long and expensive one. Perhaps the greatest challenge along this path will be social. Will we as citizens of the world be able to pull together the teams of experts capable of developing an HIV vaccine and the resources required to support them? Such teams must have capabilities that include laboratory science, vaccine development and manufacture, vaccine clinical testing, regulatory and ethical oversight and approval, and public health. Furthermore, will those who are entrusted with protecting the publicûs health be able to accept the challenge and generate the interest of all necessary parties required to take on this large task? The social value for an HIV vaccine is immense, but translating that social value into real-world financial investment for a vaccine is not straight forward. In spite of being a small country, since 1992 Thailand has put a tremendous effort in controlling its HIV epidemic using a variety of preventive and therapeutic interventions, including a strong commitment to HIV vaccine research and development. Thailand was the first country that adopted a National AIDS Vaccine Plan in place and has moved forward in this area continuously and persistently during the past decade. xv

24 INTRODUCTION This book summarizes more than ten years of collective experience in the planning and implementation of HIV vaccine research in Thailand. A selected group of authors from Thailand and from abroad, contributed with chapters that tell a compelling story that needs to be shared with others. After describing the global challenge of developing an HIV vaccine, chapter 2 of the book provides background information on the epidemiology and virology of the AIDS epidemic in Thailand, which provide the justification and scientific bases for the vaccine work conducted in the country. Subsequent chapters in chapter 3 provide an overview of HIV vaccine research in Thailand, and describe the development of the National AIDS Vaccine Plan and the process for scientific and ethical review of protocols for clinical trials of candidate HIV vaccines. In analyzing the reasons for success of the HIV vaccine program in Thailand, it becomes clear that a collaboration between equals, involving several research groups in Thailand and different international collaborators, was key and that experience is described in chapter 4 of the book. The first HIV vaccine trial in Thailand was initiated in 1993, and several chapters in chapter 5 of the book describe the experiences of different groups in Thailand in the conduct of phase I/II clinical trials of HIV candidate vaccines. chapter 6 describes the development of cohorts in preparation for phase III trials of HIV vaccines, and chapter 7 of the book discusses the two phase III trials conducted or ongoing in Thailand, including important issues related to data management and community participation. These chapters describe, not the theory of how HIV vaccines are developed and evaluated, but they tell a real story of successes and failures. Such real-world experience is essential in order to advance this complex field. Without it no vaccine will ever be developed. Yet, undertaking this work in Thailand has not been trivial, and it will continue to require commitments and risk taking at all levels from central government to village volunteers. But success will only be achieved if the Thai commitment is mirrored at a global level, with other countries and organizations following the example of Thailand. xvi

25 For this book, many busy people have taken the time to document Thailandûs HIV vaccine efforts so that others can hopefully benefit from the Thai experience. May all who use it benefit and may it help, in some small way, to eventually develop a safe and effective HIV vaccine for the world. Punnee Pitisuttithum Donald P. Francis Jose Esparza Prasert Thongcharoen CHAPTER 1 xvii

26