Scaling Up Treatment for the Global AIDS Pandemic
CHALLENGES AND OPPORTUNITIES
James Curran, Haile Debas, Monisha Arya,
Patrick Kelley, Stacey Knobler, and Leslie Pray, Editors
THE NATIONAL ACADEMIES PRESS
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract No. NO1-OD-4-2319 between the National Academy of Sciences and the U.S. Department of Health and Human Services, and contract 32467 between the National Academy of Sciences and the Bill and Melinda Gates Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
Library of Congress Cataloging-in-Publication Data
Institute of Medicine (U.S.). Committee on Examining the Probable Consequences of Alternative Patterns of Widespread Antiretroviral Drug Use in Resource-Constrained Settings.
Scaling up treatment for the global AIDS pandemic : challenges and opportunities / Committee on Examining the Probable Consequences of Alternative Patterns of Widespread Antiretroviral Drug Use in Resource-Constrained Settings, Board on Global Health ; James Curran . . . [et al.], editors.
p. ; cm.
Includes bibliographical references.
ISBN 0-309-09264-7 (pbk.)
1. AIDS (Disease) 2. AIDS (Disease)—Developing countries. 3. Antiretroviral agents—Developing countries.
[DNLM: 1. HIV Infections—drug therapy. 2. Antiretroviral Therapy, Highly Active. 3. Disease Outbreaks—prevention & control. 4. Health Planning—organization & administration. WC 503.2 I59s 2004] I. Curran, James W. II. Title.
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Copyright 2005 by the National Academy of Sciences. All rights reserved.
Cover: Detail of “Women’s Faces” by Lilian Nabulime, wood and metal, 2002. Lilian Nabulime is a respected Ugandan artist whose works focus on HIV and AIDS awareness and African women. Photograph by Alexander Calder, Curator, The Art Room, San Francisco, CA.
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COMMITTEE ON EXAMINING THE PROBABLE CONSEQUENCES OF ALTERNATIVE PATTERNS OF WIDESPREAD ANTIRETROVIRAL DRUG USE IN RESOURCE-CONSTRAINED SETTINGS
JAMES CURRAN (Cochair),
Rollins School of Public Health, Emory University, Atlanta, Georgia
HAILE DEBAS (Cochair),
University of California, San Francisco, Global Health Sciences, San Francisco, California
Department of Medicine, Bioethics Centre, University of Cape Town, South Africa
University of California, Los Angeles, School of Medicine, Los Angeles, California
J. BROOKS JACKSON,
Johns Hopkins University School of Medicine, Baltimore, Maryland
Partnership for Health ReformPlus Project, Abt Associates, Inc., Bethesda, Maryland
Joint Clinical Research Center, Uganda, East Africa
University of Cape Town, South Africa
University of California, San Francisco
Medical Research Council of South Africa
AIDS Research Institute, University of California, San Diego
Harvard Medical School, Division of AIDS, Boston, Massachusetts
PATRICK KELLEY, Board Director
STACEY KNOBLER, Senior Program Officer
MONISHA ARYA, Christine Mirzyan Science and Technology Policy Intern
ALLISON BERGER, Program Assistant
LESLIE PRAY, Science Writer
BOARD ON GLOBAL HEALTH
DEAN T. JAMISON (Chair),
University of California, Los Angeles
JAIME SEPÚLVEDA AMOR,
Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México
World Health Organization, Geneva, Switzerland
DONALD M. BERWICK
(IOM Council Liaison), Harvard Medical School, and
President and CEO,
Institute of Healthcare Improvement
JO IVEY BUFFORD,
Robert F. Wagner Graduate School of Public Service, New York University, New York, New York
DAVID R. CHALLONER
(IOM Foreign Secretary), University of Florida, Gainesville
Harvard School of Public Health, Boston, Massachusetts
Department of Infectious Diseases and the Center for Global Health, University of Virginia School of Medicine, Charlottesville, Virginia
Nuclear Threat Initiative, Washington, DC
Boston University School of Public Health, Boston, Massachusetts
Emory University, Atlanta, Georgia
ADEL A. F. MAHMOUD,
Merck Vaccines, Whitehouse Station, New Jersey
School of Public Health, Yale University, New Haven, Connecticut
MAMPHELA A. RAMPHELE,
The World Bank, Cape Town, South Africa
MARK L. ROSENBERG,
The Task Force for Child Survival and Development, Emory University, Atlanta, Georgia
U.S. Government Vaccine Stockpile Program, Potomac, Maryland
IOM Board on Global Health Staff
PATRICK KELLEY, Director
DIANNE STARE, Research and Administrative Assistant
GARY WALKER, Finance Officer
HARRIET BANDA, Senior Project Assistant
ALLISON BERGER, Project Assistant
TIMOTHY BRENNAN, Science and Technology Policy Intern
STACEY KNOBLER, Senior Program Officer
KATHERINE OBERHOLTZER, Research Assistant
LAURA SIVITZ, Research Associate
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Roy M. Anderson, Imperial College, London
Stefano Bertozzi, National Institute of Public Health, Cuernavaca, México
Charles C. J. Carpenter, The Miriam Hospital, Brown University, Providence, Rhode Island
James Hakim, University of Zimbabwe, Harare, Zimbabwe
King K. Holmes, University of Washington, Seattle, Washington
Joseph-Matthew Mfutso-Bengo, University of Malawi, Chichin, Malawi
Philip C. Onyebujoh, World Health Organization, Geneva, Switzerland
George Rutherford, University of California, San Francisco
Catherine M. Wilfert, Elizabeth Glaser Pediatric AIDS Foundation, Duke University, Professor Emeritus, Durham, North Carolina
Gina Wingood, Emory University, Atlanta, Georgia
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Helen Smits, Fulbright Lecturer, Eduardo Mondlane University, Maputo, Mozambique; and Bernard Lo, University of California, San Francisco. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
Today humanity is faced with monumental decisions on how best to apply wealth and scientific know-how to fight the global AIDS crisis, a crisis that each day kills more than 5,000 people in the developing world.
The pandemic of HIV infection that has emerged over the last 25 years has progressed to the point where more than 40 million people are infected with a virus that is universally fatal without treatment. The vast majority of these infected individuals live in some of the poorest countries of the world. About 6 million of them are now in need of antiretroviral therapy, and over the next decade, most of the remaining persons currently infected will progress to that point as well. Perhaps most sobering is that, beyond the current burden, the incidence of HIV infection continues to surge, with about 5 million new cases per year.
Clearly, resources now being mobilized to address this crisis will have to increase steadily and be sustained for decades to come. Attention to both HIV prevention and care is urgently needed. In our rush to be humane, however, we run the risk of sowing the seeds of failure if we do not base programs on solid, evidence-based principles of medical science and public health practice. Such failures would be devastating to all those in need of treatment now and into the future. In addition, by challenging the scientific credibility and feasibility of the whole enterprise, program failure would pose a threat to the willingness of donors to sustain the heroic global response upon which they have embarked. We must, therefore, proceed with caution, while at the same time tolerating no unnecessary delay in
heeding the clear moral imperative to halt the devastation caused by this terrible disease.
Typically, individuals infected with HIV are in the prime of their lives, shouldering significant responsibilities for their families and their societies. In addition, thousands of infants are born each year to infected mothers and are at risk to develop HIV infection or to become orphans as their parents die, or both. The high incidence of AIDS in some countries, moreover, is threatening their social, political, economic, and military institutions, thus posing a threat to regional and global security. In African countries with the highest HIV prevalence rates in excess of 20 percent, key societal institutions are at widespread risk of collapse. The potential consequences of this disintegration for local and international peace, prosperity, and freedom are great. Although the world community today has the resources and much of the scientific know-how to begin to stem this devastation, the earliest global responses have been slow in coming and not always well informed by current science and lessons learned from earlier efforts. Furthermore, members of the international community who are leaders in the fight against AIDS in the developing world need to coordinate and harmonize their efforts.
The most-developed countries in the world have benefited from life-extending highly active antiretroviral treatment regimens for about 8 years. Tens of thousands of afflicted persons have seen their fatal infections converted into chronic conditions such that with high-quality care, they may enjoy many more years of healthy and productive life. Costly lessons have been learned in providing this care, however, lessons that must inform newly established treatment programs in resource-constrained countries so as to ensure that they operate with maximal effectiveness and efficiency.
Antiretroviral therapy is a highly demanding form of treatment even in sophisticated medical environments with the best of resources. Complex multidrug regimens must be followed with scrupulous attention to adherence to prevent treatment failure and slow the emergence of drug resistance. Fixed-dose combinations offer significant promise for improving adherence by simplifying these regimens; at the same time, however, this form of compounding presents clinical and pharmacologic quality assurance issues that should not be underappreciated. The specter of drug resistance and treatment failure, a common consequence of imperfect adherence, looms particularly large in resource-poor settings, where the considerably greater expense of second-line regimens may limit their availability. Monitoring for the emergence of resistance and toxicity is also hampered in resourceconstrained countries by limited access to laboratories with the relevant capacity. To meet these challenges, well-designed logistic, clinical, and patient support systems are critical.
With the mobilization of billions of dollars to initiate antiretroviral
therapy in resource-constrained settings through such mechanisms as the Global Fund to Fight AIDS, Tuberculosis, and Malaria and the U.S. Emergency Plan, the greatest obstacle to significantly prolonging millions of lives may be less lack of access to potent antiretroviral drugs than a looming shortage of qualified persons to deliver and monitor care in a manner that will produce the long-term outcomes sought. Many of the health care systems charged with caring for those infected are seriously understaffed to do so, and the talent required to meet the projected need is just not present locally in adequate amounts. A range of mechanisms, both traditional and innovative, will have to be employed to insert the many types of needed expertise.
While we must move ahead boldly, making use of the best current knowledge, there is much to be learned in the process. Systematic learning while doing will be critical to the ultimate success of these historic initiatives to scale up antiretroviral therapy. Such learning must be accomplished through rigorous monitoring and evaluation of the diversity of programs employed from country to country and in countless villages, towns, and cities. Targeted evaluations and a rigorous program of operational and applied clinical and behavioral research to answer specific questions must be thoughtfully designed, well coordinated, and funded from the beginning with ample dedicated resources.
The legacy of the United States and its international partners, and indeed of the entire global community, in the early 21st century will depend on how we respond to the challenges of the day with the resources at our disposal. While the terrorist threat may appear to dominate, the extent of our capacity to act with a humanitarian regard for those societies being devastated by AIDS may ultimately define the history of our time. We have recognized the inexorable march of HIV for over 20 years and have until recently placed relatively little emphasis on our capacity to deal with its worst manifestations—the decimation being experienced by some the poorest nations of the world. Today, at last, the international medical community has at its disposal the political backing, the know-how, and the resources to begin to meet the challenge of HIV prevention and care in the developing world. We must not abandon those we start on therapy, nor can we ignore the pleas of the millions more who will subsequently make a claim on our humanity. We must act now, and we must act well.
James Curran, M.D., M.P.H.
Haile Debas, M.D.
The committee was aided in its deliberations by the testimony and advice of many knowledgeable and experienced individuals, and the efforts of dedicated committee members and staff. Consultants to the committee contributed ideas and report materials. The committee thanks consultants Owen Smith, Abt Associates, Inc.; and Angela Wasunna, The Hastings Center, for their submission of commissioned papers that appear in the appendixes of this report.
The committee acknowledges with appreciation the testimony of many individuals committed to addressing the needs of individuals and communities affected by HIV/AIDS around the world. These individuals are: Diane Bennett, World Health Organization; Stefano Bertozzi, National Institute of Public Health, Cuernavaca, Mexico; Yasmin Chandani, John Snow, Inc.; Rachel Cohen, Campaign for Access to Essential Medicines, Médecins sans Frontières; Steven Deeks, University of California, San Francisco; Victor DeGruttola, Harvard School of Public Health; Paul DeLay, UNAIDS; Sam Dooley, Centers for Disease Control and Prevention; Wafaa El-Sadr, Columbia University and Harlem Hospital; Daniel Fitzgerald, Cornell University Medical College; Eric Goosby, Pangea Global AIDS Foundation; John Idoko, Jos University Teaching Hospital, Jos Nigeria; Brooks Jackson, Johns Hopkins University School of Medicine; Jim Kim, World Health Organization; Mark Kline, Baylor College of Medicine/Texas Children’s Hospital; Ronaldo Lima, International AIDS Vaccine Initiative; Emi MacLean, Médecins sans Frontières; Lynn Margherio, The Clinton Foundation HIV/ AIDS Initiative; Rashad Massoud, Quality and Performance Institute, University Research Co., LLC; Anthony Mbewu, Medical Research Council of South Africa; John McNeil, National Minority AIDS Education and Training Center, Howard University; Lynne Mofenson, National Institute of Child Health and Human Development, National Institutes of Health; Carla Makhlouf Obermeyer, World Health Organization; Joseph O’Neil, Office of Global AIDS, U.S. Department of State; Mead Over, The World Bank;
Thomas Quinn, Johns Hopkins University School of Medicine; Robert Redfield, University of Maryland, Baltimore; Mauro Schechter, Universidade Federal do Rio de Janeiro, Brazil; Bernhard Schwartlander, The Global Fund to Fight AIDS, Tuberculosis, and Malaria; and Angela Wasunna, The Hastings Center. The agenda for the information-gathering workshop in which these individuals participated appears in Appendix A of the report.
Finally, and in particular, the committee would like to express its deep appreciation of the Institute of Medicine (IOM) staff who facilitated its work. We especially thank Monisha Arya, Patrick Kelley, Stacey Knobler, and Leslie Pray for translating and transforming the discussions and deliberations of the committee into final prose. The committee is grateful to Karl Galle, Katherine Oberholtzer, and Dianne Stare, for their efforts in addressing the information and research verification needs of the study and preparing the final manuscript for publication. Special thanks to Allison Berger and Amy Giamis for their extra efforts and repeated attention to the logistical support of the study. Others within the IOM and the National Academies who were instrumental in seeing the project to completion were Harriet Banda, Jennifer Bitticks, Tim Brennan, Rachel Cohen, Janice Mehler, Jennifer Otten, Bronwyn Schrecker, Laura Sivitz, and Sally Stanfield. Thanks are also expressed to editorial consultants Rona Briere and Alisa Decatur.
This report was made possible by the generous support of the Fogarty International Center (FIC), the Office of AIDS Research at the National Institutes of Health (OAR), and the Bill and Melinda Gates Foundation (GF). Additional support for funding international travel of workshop speakers was provided by the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNAIDS; and the Centers for Disease Control and Prevention Global AIDS Program. The committee is appreciative of their support and of the commitment and productive efforts of Jerry Keusch and Sharon Hrynkow (FIC); Jack Whitescarver (OAR); and Helene Gayle (GF).
Approximately 40 million people worldwide are infected with HIV, and 6 million suffering from AIDS need antiretroviral therapy (ART) now. Yet only about 400,000 people in resource-poor nations have access to treatment, despite the fact that these countries often have the highest infection rates of HIV. The largely unchecked pace of the infection and its impact on the social, political, and economic dimensions of individuals and communities continue to undermine the development of entire countries and regions of the world.
Therefore, what must be emphasized is the need for the global community to act now. Growing recognition of this human and societal catastrophe, combined with the increased understanding and availability of technical tools necessary to halt its devastating progress, have mobilized political will and financial resources worldwide to bring treatment options within the reach of those most in need.
Equally important to scaling-up the global response to HIV/AIDS will be the need to act well. The availability of inexpensive drugs alone will not ensure the successful prolongation of millions of lives. Experience with ART in wealthy nations has led many experts to heed concerns over the suboptimal introduction of these drugs. Considerable attention to strategies that promote the highest levels of patient adherence to drug regimens will be needed to avoid treatment failure and the more rapid development of drug-resistant strains of the virus.
Key to implementing these adherence strategies, as well as to delivering effective ART, will be tens of thousands of health care and management
personnel with the experience and training to treat millions of people with a disease that requires a complicated and long-term regimen. A workforce of this magnitude does not currently exist in most resource-poor nations, and its mobilization could have negative collateral effects on existing health programs through diversion of scarce resources. Significant shortages in trained personnel must be addressed immediately and energetically through innovative governmental and private-sector programs. Such efforts to address carefully defined weaknesses should seek to bring health care and other professionals from resource-rich nations into developing countries, while supporting robust efforts to train and educate a national workforce that will continue to expand sustainable HIV/AIDS treatment and prevention initiatives well into the future.
Promoting a culture of learning by doing will be an essential component of the success of ART scale-up. As a first priority, ongoing monitoring and evaluation of the many aspects of ART programs should be viewed as being as fundamental to scale-up as the antiretroviral drugs themselves.
In moving forward rapidly to stem the tragic progress of HIV/AIDS, it must be recognized that there is still much to be revealed about the most effective ways to operate large-scale ART. Existing guidelines and treatment regimens will need to be improved and adapted to meet the highly variable needs of populations with significantly different cultural, economic, epidemiological, and technical profiles.
It bears emphasizing that the global problem of HIV/AIDS will be present for decades despite prevention and treatment interventions. With a projected 5 million additional people infected by HIV each year, the numbers needing treatment will continue to increase. Once ART has been initiated, we must not abandon the millions started on therapy or ignore the pleas of the tens of millions more who will soon need these medicines. Even short-term interruptions in support could be clinically disastrous and ethically unconscionable by allowing successfully suppressed HIV infections to emerge in drug-resistant forms against which no affordable interventions would be successful. Thus, ART must not be seen simply as a short-term goal or the end point of a 5-year plan. Scale-up of HIV/AIDS treatment and prevention is an urgently needed public health endeavor of unprecedented scale. Its noble intentions must be matched by an equally unprecedented commitment to sustained action against one of the worst plagues in human history.