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Confront r l Directions for Public Health, Health Care, and Research Institute of Medicine National Academy of Sciences NATIONAL ACADEMY PRESS Washington, D.C. 1986

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NATIONAL ACADEMY PRESS ~ 2101 Constitution Ave., NW ~ Washington, DC 20418 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 report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The National Academy of Sciences was established in 1863 by Act of Congress as a private, nonprofit, self-governing membership corporation for the furtherance of science and technology, required to advise the federal government upon request within its fields of competence. Under its corporate charter the Academy established the National Research Council in 1916 and the National Academy of Engineering in 1964. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Support for this project was provided by the National Research Council (NRC) Fund, a pool of private, discretionary, nonfederal funds that is used to support a program of Academy-initiated studies of national issues in which science and technology figure significantly. The NRC Fund consists of contributions from several sources: a consortium of private foundations, including the Carnegie Corporation of New York, the Charles E. Culpeper Foundation, the William and Flora Hewlett Foundation, the John D. and Catherine T. MacArthur Foundation, the Andrew W. Mellon Foundation, the Rockefeller Foundation, and the Alfred P. Sloan Foundation; the Academy Industry Program, which seeks annual contributions from companies that are concerned with the health of U.S. science and technology and with public policy issues with technological content; and the National Academy of Sciences and the National Academy of Engineering endowments. Library of Congress Catalog~ng-in-Publication Data Institute of Medicine (U.S.). Confronting AIDS. Report prepared by the Committee on a National Strategy for AIDS of the Institute of Medicine. Includes bibliographies and index. 1. AIDS (DiseaseWPrevention~overnment policy-United States. 2. AIDS (Disease - United States- Prevention. 3. AIDS (Disease0Research~overnment policy-United States. 4. AIDS (DiseaseWRe- search-United States. 5. AIDS (DiseaseWTreatment~overnment policy-United States. 6. AIDS (DiseaseWTreatment-United States. I. Institute of Medicine (U.S.). Committee on a National Strategy for AIDS. II. Title. [DNLM: 1. Acquired Immunodeficiency Syndrome. 2. Health Policy-United States. WD 308 I59cl ~. ~ . . ~ . . .AA RA644.A25I57 1986 362.1'9797'9200973 86-23779 ISBN 0-309-03699-2 Copyright @) 1986 by the National Academy of Sciences First Printing, October ~ 9~6 Second Printing, January ~ 907 Third Printing, March 1907 Fourth Printing, March 1987 Fifth Printing, June ~ 9~7 Sixth Printing, September ~ 987 Seventh Printing, December 19S7 Eighth Printing, June ~ 988 Ninth Printing, September ~ 9 BS Tenth Printings,, October 1989 No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purposes of official use by the U.S. government. Printed in the United States of America

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Committee on a National Strategy for AIDS STEERING COMMITTEE DAVID BALTIMORE (Cochair), Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge SHELDON M. WOLFF (Cochair), Tufts University School of Medicine and New England Medical Center Hospital, Boston JOHN J. BURNS, Roche Institute of Molecular Biology, Nutley, New Jersey LEON EISENBERG, Harvard Medical School, Boston BERNARD N. FIELDS, Harvard Medical School, Boston HARVEY V. FINEBERG, Harvard School of Public Health, Boston FRANK LILLY, Albert Einstein College of Medicine, Bronx JUNE E. OSBORN, School of Public Health, University of Michigan, Ann Arbor MARGERY W. SHAW, University of Texas Health Science Center, Houston PAUL VOLBERDING, San Francisco General Hospital IRVING WEISSMAN, Stanford University School of Medicine HEALTH CARE AND PUBLIC HEALTH PANEL SHELDON M. WOLFF (Chair), Tufts University School of Medicine and New England Medical Center Hospital, Boston JAMES CHIN, California State Department of Health Services, Berkeley WILLIAM J. CURRAN, Harvard School of Public Health, Boston DAVID W. FRASER, Swarthmore College, Swarthmore, Pennsylvania JEFFREY E. HARRIS, Massachusetts Institute of Technology, Cambridge ARTHUR LIFSON, Equitable Life Assurance Society of the United States, New York City DOROTHY NELKIN, Cornell University, Ithaca, New York JUNE E. OSBORN, School of Public Health, University of Michigan, Ann Arbor SAMUEL W. PERRY, Cornell University Medical Center, New York City PAUL VOLBERDING, San Francisco General Hospital LeROY WALTERS, Kennedy Institute of Ethics, Georgetown University, Washington, D.C. RESEARCH PANEL DAVID BALTIMORE (Chair), Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge LEON EISENBERG, Harvard Medical School, Boston . . .

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RESEARCH PANEL (Continued) BERNARD N. FIELDS, Harvard Medical School, Boston JEROME E. GROOPMAN, Harvard Medical School, Boston MAURICE R. HILLEMAN, Merck Institute for Therapeutic Research, Merck Sharp & Dohme Research Labs, West Point, Pennsylvania RICHARD T. JOHNSON, Johns Hopkins University School of Medicine, Baltimore, Maryland ROBERT F. MURRAY, Jr., Howard University College of Medicine, Washington, D.C. ROLAND K. ROBINS, Molecular Research Institute and ICN Pharmaceuticals, Costa Mesa, California P. FREDERICK SPARLING, University of North Carolina School of Medicine, Chapel Hill CLADD E. STEVENS, New York Blood Center, New York City HOWARD M. TEMIN, University of Wisconsin School of Medicine, Madison IRVING WEISSMAN, Stanford University School of Medicine EPIDEMIOLOGY WORKING GROUP CHAIRMAN J. THOMAS GRAYSTON, University of Washington, Seattle STAFF ROY WIDDUS, Project Director and Director, Division of International Health DEBORAH COTTON, Deputy Project Director MARK FEINBERG, Staff Officer JEFF STRYKER, Staff Officer JUDE PAYNE, Research Assistant KAREN ZWEIG, Research Assistant GAIL SPEARS, Administrative Secretary STEVE OLSON, Project Editor DOROTHY SAWICKI, Book Editor, National Academy Press CAROL COFIELD, Secretary CAREY O'BRIEN, Secretary KATHLEEN ACHOR, Secretary CONSULTANTS PETER E. DANS, Johns Hopkins Medical Institutions, Baltimore, Maryland JESSE GREEN, New York University Medical Center, New York City 1V

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Preface In October 1985 the Institute of Medicine devoted its annual meeting to the subject of acquired immune deficiency syndrome (AIDS). The infor- mation presented at that meeting has been summarized in a nontechnical volume entitled Mobilizing Against AIDS: The Unfinished Story of a Virus (Harvard University Press, 1986), which surveys knowledge on AIDS and the issues raised by the disease. That annual meeting was not intended to develop recommendations about the best course of action for dealing with the problems it surveyed, but the Institute of Medicine realized that recommendations were needed and that, to develop them, national leadership was essential. As a result, in early 1986 the presidents of the National Academy of Sciences (NAS) and the Institute of Medicine (IOM), with the approval of the councils of these organizations, decided to initiate a special effort to assess the extent of the problems arising from AIDS and to propose an appropriate national response. The congressional charter establishing the National Academy of Sciences, under which it and the Institute of Medicine operate, specifies that they shall undertake studies of issues of vital importance to the nation. This report results from such self-initiated activity. The topics to be addressed in the study were specified as follows: The committee shall assess the current understanding of the virus that causes acquired immune deficiency syndrome (AIDS), its transmission, the natural history of infection and associated disease, the epidemiology of conditions associated with the virus, and the likely trends in these. v

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vi PREFACE The committee also shall review the nation's response to AIDS both in the public and private sector and the current planning in regard to: research necessary for prevention and treatment provision of care and its financing public health measures designed to control the disease. The committee shall evaluate methods whereby the ultimate goals of controlling and combating the disease may be achieved. Questions to be addressed should include, but are not necessarily limited to, the following: Are there neglected research opportunities or needs with regard to the biology and epidemiology of the virus, the animal models of infection and disease, or the prospects for vaccines or antiviral agents? What are the impediments to the most expeditious pursuit of these opportu- nities and needs, and how can they be overcome? Specifically, what mechanisms should be instituted to achieve promotion of productive research, timely utiliza- tion of new knowledge, optimal communication among persons engaged in research and development (and with health care and public health professionals), integration and coordination of the R&D effort, recruitment of appropriate investigators, and the optimal involvement of industry? Is the care of AIDS and AIDS-related complex (ARC) patients (and seropositive persons) properly coordinated? What are the best approaches to the provision of care and what are the local, regional, and national implications of these models for the health care system? How are the costs of care being met? Are there ways in which these costs could be met in a more rational and/or equitable fashion? What public health measures (including educational programs) are desirable in light of present knowledge and circumstances? By whom should these be promoted, implemented, coordinated, and revised? What are the legal and ethical issues raised by the questions posed above; in particular, in the formulation of public health policy, how is a balance best achieved between the interests of the public and those of the individual? How should the United States address the international ramifications of the problem of AIDS? What will be its magnitude; what is the appropriate role for the United States; and what are its responsibilities? The committee shall prepare a report outlining a strategy (or strategies) whereby these concerns can be addressed. The report shall contain recommen- dations for its implementation directed to the Executive Branch, the Congress, the research community, those who treat patients, state and local governments, corporate leadership, and the public. The report shall include a description of the basis for the committee's conclusions. To prepare this report, a committee with an impressive breadth of credentials was established. To cover the broad range of issues raised in combating AIDS, two panels were constituted, one addressing issues in research, the other addressing issues in health care and public health. To

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PREFACE vii integrate the activities of the panels, a steering group was formed, consisting of four members from each panel and four at-large members. Collectively, the panels and the steering committee comprised individuals with expertise in molecular biology, virology, immunology, epidemiol- ogy, neurology, psychiatry, infectious diseases, general medicine, health care, public health, economics, law, ethics, and other disciplines. They represented research experience in academia, several branches of the federal government, and industry, with substantial experience in manag- ing research and development projects in all three of these areas. In addition, the panels and the steering committee included individuals with experience in developing and implementing public health programs at the national, state, and local levels, as well as those closely involved in the care of patients. The councils of the National Academy of Sciences and the Institute of Medicine requested that a report be produced by the committee within six months of its initial meeting, reflecting the urgency with which they felt the problem should be addressed. In response, the committee undertook an intensive schedule of activities. Each panel held four meetings, which were attended by many of the at-large members of the steering commit- tee. Also, two working groups were formed, one consisting of approxi- mately 30 individuals who studied both the short- and long-term epidemi- ology of the disease, and the other a somewhat smaller group that met on two occasions to discuss issues in the financing of health care for AIDS patients. The committee held two public meetings, one in San Francisco and one in New York City, where many individuals concerned with various problems raised by AIDS expressed their views. In addition to the public meetings, the committee invited a large number of individuals from the scientific, health care, and public health communities to contribute their thoughts. Many excellent papers were prepared at the committee's request and will be available upon request to the Institute of Medicine (see Appendix H). Many individuals involved in AIDS-related activities were also kind enough to submit prepublication data, greatly aiding the committee's awareness of ongoing research. Committee and staff members participated in a workshop held by the Public Health Service at Coolfont, Berkeley Springs, West Virginia, June 4-6, 1986, to produce a plan for the prevention of AIDS and the control of the AIDS virus. A number of committee members and a representative of the staff also attended the Second International Conference on AIDS in Paris, June 22-25, 1986, where much new information was presented. In July 1986 the steering committee held its final meeting in Woods Hole, Massachusetts, to integrate the contributions from the panels and the working groups.

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viii PREFACE TERMINOLOGY AIDS poses a number of problems related to terminology. First, the etiologic agent of AIDS has been given several different names, including lymphadenopathy-associated virus (LAV), human T-cell lymphotropic virus type III (HTLV-III), and AIDS-associated retrovirus (ARV). The committee followed the usual practice of NAS/IOM committees in using the name recommended by the appropriate international body charged with giving advice on nomenclature. In this case, the appropriate body is the International Committee on the Taxonomy of Viruses, a subcommit- tee of which has proposed that the virus be called human immunodefi- ciency virus (HIV). This designation for the virus is used throughout this report. Terminology related to AIDS and other conditions related to HIV infection may also be confusing. The term AIDS itself was coined as a surveillance definition for epidemiologic purposes. It does not include the full spectrum of conditions now known to be associated with lIIV infection. Reference to the "AIDS epidemic" has become ubiquitous in discus- sions and publications on this topic. It must be understood, however, that the epidemic in its full extent includes not only individuals with AIDS but other infected individuals who have less severe manifestations of the disease or who are asymptomatic. (In some sense, the epidemic can even be said to encompass reactions such as fear of the disease and of the virus among the general public.) Indeed, because infection of humans with HIV is a relatively new phenomenon, the full spectrum of signs and symptoms that the virus may cause is yet to be known. Furthermore, the manifes- tations of HIV infections and immunodeficiency reflect, at least in part, the environmental pathogens to which individuals are exposed. Thus, these manifestations may appear to vary in different population groups in different parts of the world, but they still resect the basic, underlying HIV infection. In general, the evolution of terminology related to HIV- associated conditions should be regarded as natural and desirable as our knowledge of the pathogen and its consequences increases. There are other problems of terminology related to AIDS. Certain groups-for example, male homosexuals and intravenous drug users- have been designated as being at high risk of contracting the disease. However, the designation "at high risk" encompasses more people than is necessary, because not all members of these groups are at high risk of being infected with HIV. A more appropriate designation might be "persons who engage in high-risk behaviors," and references in this report to "high-risk groups" should be so interpreted. Furthermore, references to high-risk groups may lead persons outside of these groups to believe mistakenly that they are not susceptible to HIV infection even if

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PREFACE 1X they engage in high-risk activities. It may also lead individuals to consciously or unconsciously deny that they are at risk. For example, a man who has had infrequent homosexual contacts may regard himself as predominantly heterosexual and therefore not in danger of infection. This can lead to misconceptions about the desirability of taking action to avoid infection or about whether infection may have already occurred. Identifying the risk of infection as being associated with certain "high-risk behaviors" is also not without problems. This is particularly so in the area of sexual transmission, where a multiplicity of sexual partners, homosexual or heterosexual, has been associated with a high risk of becoming infected. Unfortunately, some may interpret this to mean that many partners are required for a person to become infected. In fact, it merely represents a statistical phenomenon whereby the chances of having intercourse with an infected person increase as the number of partners increases. The term "intravenous drug use" presents additional difficulties. In this report the term implies the intravenous administration of illicit drugs such as heroin for nonmedical purposes. Individuals who engage in this activity may or may not be addicted, and some may not regard their use of such drugs as abuse. Care has been taken throughout the report to be as precise as possible. However, the reader should bear in mind potential problems of this nature when drawing conclusions from material presented here. STRUCTURE OF THE REPORT After a summary chapter that presents the report's major findings and recommendations, Chapter 2 lays out the present understanding of the disease and the current status of the AIDS epidemic, providing the essential background information upon which the committee based its conclusions and recommendations (which appear throughout succeeding chapters as well as in the summary chapter). Chapter 3 then projects the epidemic into the future, suggesting its most likely course and discussing the uncertainties that any such projections entail. It also includes a brief discussion of the resources that could be brought to bear on the problems the epidemic has generated. Chapter 4 examines the measures available now e.g., education that could alter the course of the epidemic. Chapter 5 discusses the implications of the epidemic's projections for the provision and financing of health care related to HIV infection and AIDS in the United States. Chapter 6 identifies areas of research that will be critical in the long term for devising better means of prevention and treatment. Chapter 7 looks at international aspects of HIV infection and AIDS and at the United States' contribution to solving those problems.

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x PREFACE Given the complex nature of the problems and the time and resources available, the committee did not attempt to prepare a definitive mono- graph on AIDS or to make explicit recommendations on all of the problems related to the disease. Rather, it identified the most crucial problems and suggests, when necessary, mechanisms for addressing them. Some of these problems can be addressed by agencies that already exist; others may need new mechanisms or require the convening of disparate groups working together to solve them. During the preparation of the report, the committee was continually reminded that it was assessing a "moving target," because the problem of HIV infection was evolving as it was being studied. Consequently, this report represents the committee's evaluation as of August 1986. The pace of developments in this field has also contributed to one of the committee's major recommendations that the problem should be mon- itored on a continuing basis. Limited time precluded the committee's addressing certain important areas as fully as would have been desirable. The areas needing further consideration are identified in the report. As discussed in Chapter 1, the committee hopes that a mechanism will be put in place to take up the important issues in more detail. ACKNOWLEDGMENTS The committee wishes to thank the many persons who took time from their activities to assess the current status of their fields for purposes of this report (see Appendix J). In addition, all committee members gave unstintingly of their time to this endeavor. As cochairmen, we thank them for their devotion to this important work. Finally, we wish to acknowl- edge the excellent substantive and organizational assistance provided to the committee by the staff of the IOM-NAS headed by Roy Widdus. DAVID BALTIMORE Director, Whitehead Institute for Biomedical Research, and Professor of Biology, Massachusetts Institute of Technology SHELDON M. WOLFF Chairman, Department of Medicine, Tufts University School of Medicine, and Physician-in-Chief, New England Medical Center Hospital

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Contents ABSTRACT CONFRONTING AIDS: SUMMARY AND RECOMMENDATIONS Status of the Epidemic, 5 Infection and Transmission, 6; Clinical Manifestations of the Disease, 7; Statistical Dimensions of the Epidemic, 7 The Future Course of the Epidemic, ~ Opportunities for Altering the Course of the Epidemic, 9 Public Education, 9; Public Health Measures, 13; Funding for Education and Other Public Health Measures, 16; Discrimination and AIDS, 19 Care of Persons Infected with HIV, 19 Health Care Costs Resulting from HIV Infection, 21; The Financing of Health Care for HIV-Related Conditions, 22 Future Research Needs, 23 Basic Research, 23; The Natural History of HIV Infection, 23; Epidemiologic Approaches, 24; Animal Models, 25; Antiviral Agents, 25; Vaccines, 26; Social Science Research Needs, 27; Funding for Research on AIDS and HIV, 28 X1

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xii CONTENTS International Aspects of AIDS and H]:V Infection, 28 Rationale for U.S. International Involvement, 29; Risks of Infection Outside the United States, 29; International Research Opportunities, 30 Guidance for the Nation's Efforts, 31 What Is Needed?, 32; Establishment of the Commission, 32 Major Recommendations, 33 2 UNDERSTANDING OF THE DISEASE AND DIMENSIONS OF THE EPIDEMIC....... The Causative Agent of AIDS, 38 Features of Retroviruses, 40; Related Viruses, 41 Pathogenesis of AIDS, 42 Natural History of the Disease, 44 Clinical Manifestations of HIV Infection, 46 Opportunistic Infections, 46; Kaposi's Sarcoma, 47; Other Malignancies, 48; Neurologic Complications Associated with HIV Infection, 49; Pediatric AIDS, 49 Modes of Transmission of HIV, 50 Sexual Transmission, 51; Parenteral Transmission, 52; Maternal-Infant Transmission, 56 Population Groups at Increased Risk of HIV Infection, 57 Homosexual Men, 57; Intravenous Drug Users, 59; Hemophiliacs, 60; Recipients of Blood Transfusions, 60; Heterosexual Contacts of HIV-Infected Persons, 61; Infants and Children, 61; Health Care Workers, 62 Epidemiologic Studies and Findings, 63 Surveillance, 63; National Disease Reporting, 63; Epidemiologic Research, 65; Findings of Epidemiologic Studies, 69 HIV Infection and AIDS Outside the United States, 73 African Countries, 74; Other Countries, 76 References, 77 3 THE FUTURE COURSE OF THE EPIDEMIC AND AVAILABLE NATIONAL RESOURCES ........ Projections by the Public Health Service, 85 Problems in Making Projections, 86 . 37 85

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CONTENTS xiii The Epidemic Within and Beyond High-Risk Groups, 89 The Proportion of Seropositive Individuals Who Will Develop AIDS, 91 Long-Term Prospects, 91 National Resources for Dealing with AIDS and HIV, 92 Impediments to Involvement, 92; Mechanisms for Coordinating Activities, 93 References, 94 4 OPPORTUNITIES FOR FILTERING THE COURSE OF THE EPIDEMIC ........................... Public Education, 96 What Should Be the Content of Public Education?, 97; What Are the Aims of Public Education?, 100; Who Needs Education?, 100; Who Should Do the Educating?, 103; Assessing Educational Interventions, 104; A Special Case Changing Behavior Among IV Drug Users, 105; Recommendations, 110 Public Health Measures, ~12 Tests for Infection with HIV, 113; Blood Banking, 115; Surveillance, 117; Reporting Schemes, 118; Contact Tracing and Notification, 119; Mandatory Screening, 120; Voluntary Testing, 122; Compulsory Measures, 126; Recommendations, 129 Funding for Education and Other Public Health Measures, 130 Recommendation, 133 Discrimination and AIDS, 133 Recommendations, 135 References, 135 CARE OF PERSONS INFECTED WITH HIV Roles of Health Care Providers, :139 Recommendations, 140 Health Care Settings for AIDS Patients, 141 Hospital Care, 141; Outpatient Care, 142; Community-Based AIDS Care, 143; Recommendations, 145 Needs of Specific Patient Populations, 146 . 95 . 139

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XiV CONTENTS Psychiatric and Psychosocial Support, 148 Needs of Patients with AIDS, 148; Needs of Patients with ARC, 149; Needs of Patients with Subclinical HIV Infections, 150; Needs of Seronegative Persons, 151; Recommendations, 152 Ethical Aspects of Providing Care, 153 Costs of Health Care for HIV-Related Conditions, 155 Direct Costs of Care for AIDS Patients, 156; Costs of Care for ARC Patients and Seropositive Individuals, 158; Indirect Costs of HIV-Related Conditions, 159; Cost Implications of Projected AIDS Cases, 159; Projected Hospitalization Facilities, 160; Conclusions and Recommendations, 161 Financing of Health Care for HIV-Related Conditions, 162 Sources of Financing, 162; Improving the Coverage of Health Care Costs, 165; Emerging Issues, 166; Policy Issues, 171; Conclusions and Recommendations, 172 References, 173 6 FUTURE RESEARCH NEEDS ................. The Structure and Replication of HIV, 178 Retroviral Structure, 178; Retroviral Replication, 179; Definition of the Structural and Functional Constituents of HIV, 181; Determination of the Structure of the HIV Virion, 182; Interrupting Infection by HIV, 183; Conclusions and Recommendations, 187 Natural History of HIV Infection, I89 Transmission of HIV, 189; The Immune System Response to HIV Infection, 191; The Immunologic Consequences of HIV Infection, 193; Recommendations, 198 Epidemiologic Approaches to Understanding the Transmission and Natural History of HIV Infection, 199 Recommendations on Surveillance, 199; Recommendations on Natural History of HIV Infection, 200; Recommendations on Transmission of HIV, 202; Recommendations on the Need for Improved Serologic and Virologic Tests, 203 . 177

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CONTENTS xv Animal Models, 204 HIV Infection of Chimpanzees, 205; HIV-Related Viruses in Old World Primates, 205; Lentiviruses of Ungulates, 206; Conclusions and Recommendations, 207 Antiviral Agents, 209 Drug Evaluation in Vitro, 212; Drug Evaluation in Humans, 212; Current Antiviral Agents Under Clinical Study, 213; New Antiviral Agents Against AIDS, 218; Conclusions and Recommendations, 219 Vaccines, 221 Animal Retrovirus Vaccines, 222; Vaccines Against HIV, 225; Models of Vaccine Delivery, 226; Approaches to HIV Vaccine Development and Evaluation, 228; Conclusions and Recommendations, 229 Social Science Research Needs, 230 Breaking the Chain of Transmission, 231; Reducing Public Fear and Its Effects, 234; Organizing Health and Social Services, 237; Conclusions and Recommendations, 238 Funding for Research Related to AIDS and HIV, 238 Current Levels of and Mechanisms for Funding, 239; Current NIH Funding Mechanisms, 241; Distribution of Funds Among Agencies and to Specific Research Areas, 244; Assessing Desirable Levels of Research Support, 244; Recommendations, 248 References, 249 7 INTERNATIONAL ASPECTS OF AIDS AND HIV INFECTION ............................ Projections of the Disease Outside the United States, 261 International Organizations, 263 Rationale for U.S. :international Involvement, 264 Foreign Policy Considerations, 264; Health Improvement Assistance, 265; International Spread of Diseases, 266; Opportunities for Mutually Beneficial Research, 266; Agencies and Organizations with International Responsibilities or Operations, 267; Importation, 268 Infection Risks Outside the United States, 268 Sexual Exposure, 268; Exposure Through Blood . 261

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XV} CONTENTS Transfusion, 269; IV Drug Use, 270; Use of Unsterile Needles and Implements, 270; Lack of Evidence for Transmission by Insect Vectors and Casual Contact, 271; Conclusions, 271 International Research Opportunities, 272 The U.S. Contribution to International Efforts, 274 Conclusions and Recommendations, 276 References, 277 APPENDIXES A. Clinical Manifestations of HIV Infection . . . . . . . . . . . . 281 B. Serologic and Virologic Testing 304 C. Risk of HIV Transmission from Blood Transfusion 309 D. U.S. Public and Private Sector Resources for Fighting AIDS E. The Centers for Disease Control's Surveillance Definition of AIDS .................... F. CDC Classification System for HIV Infections G. PHS Plan for Prevention and Control of AIDS 314 316 ........ 320 and the AIDS Virus 326 H. List of Background Papers 334 I. List of Presentations at Public Meetings 336 I. Acknowledgments 339 K. Biographical Notes on Committee Members 343 GLOSSARY INDEX 353 361

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Confronting A.

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