Table Of ContentAIDS Testing
Gerald Schochetman
J. Richard George
Editors
AIDS Testing
Methodology and
Management Issues
Foreword by Walter R. Dowdle
With 38 Illustrations
Springer-Verlag
New York Berlin Heidelberg London Paris
Tokyo Hong Kong Barcelona Budapest
Gerald Schochetman, Ph.D. J. Richard George, Ph.D.
Chief, Chief,
Laboratory Investigations Branch Developmental Technology Section
Division of HlV/ AIDS Laboratory Investigations Branch
National Center for Infectious Diseases Division of HIV/ AIDS
Centers for Disease Control National Center for Infectious Diseases
Atlanta, GA 30333 Centers for Disease Control
USA Atlanta, GA 30333
USA
The photograph of microtiter plates used in the cover design was provided by Dr. Gillian
Turgeon, Cornell University.
Library of Congress Cataloging-in-Publication Data
AIDS testing: methodology and management issues 1 Gerald Schochetman,
J. Richard George, editors.
p. cm.
Includes bibliographical references and index.
ISBN-13: 978-1-4684-0516-3 e-ISBN-13: 978-1-4684-0514-9
DOl: 10.1007/978-1-4684-0514-9
1. AIDS (Disease)-Diagnosis. I. Schochetman, Gerald.
II. George, 1. Richard.
[DNLM: 1. Aquired Immunodeficiency Syndrome-diagnosis.
2. Acquired Immunodeficiency Syndrome-prevention & control. 3. HIV
Infections-diagnosis. 4. HIV Infections-prevention & control.
WD 308 A288468]
RC607.A26A359 1991
616.97'92075-dc20
DNLM/DLC 91-4852
for Library of Congress
Printed on acid-free paper.
© 1992 Springer-Verlag New York, Inc.
Softcover reprint of the hardcover 1st edition 1992
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ISBN-13: 978-1-4684-0467-8
Foreword
The human immunodeficiency virus (HIV) infection and aquired immuno
deficiency syndrome (AIDS) continue to present a major challenge to
health care professionals and society throughout much of the world. In
the United States in 1989, HIV/AIDS became the second leading cause of
death among men 25 to 44 years of age and ranked eighth among causes
of death in women 25 to 44 years of age. On the basis of current trends,
HIV I AIDS is expected to rank fifth among the causes of death in women
in this age group in 1991.
Testing for the AIDS virus has become a cornerstone for surveillance
and prevention programs and for provision of appropriate medical care
for those who are infected. Current HIV tests are highly accurate. They
rank among the best diagnostic tests in use today. The controversy sur
rounding the tests now stems not from a lack of confidence in their
reliability but from the perceived social consequences of an individual
being identified as infected with the AIDS virus. With better understand
ing by the public of HIV infectionl AIDS and a greater acceptance of
those who are infected, this attitude can be hoped to change.
The public and private health care sectors have an obligation to
those who are infected by HIV and those who are at risk of infection.
For health care providers who must understand and apply testing for
detection, counseling, and care of HIV-infected persons, this book
provides a comprehensive overview of the spectrum of issues relating
to HIV testing. Available tests are discussed in terms of information
that they provide and the application of that information for the ben
efit of the patient. Other chapters provide guidance for clinical lab
oratorians on the design and safe implementation of quality HIV testing
procedures.
This book describes in clear terms all the complex elements of testing,
including (i) those who should be offered the tests, (ii) medical and
ethical considerations, (iii) the scientific principles of the tests, and (iv)
application of the tests to determine immune functions and progress of
virus infection.
v
vi Foreword
Testing for HIV is an integral component of disease control, even more
so as potential vaccines and new therapies are developed. Remarkable
progress has been made in the area of HIV testing. Most recent is the
application of the polymerase chain reaction (peR) to detect HIV infec
tion and to trace transmission and evolution of the virus. New tests and
new procedures undoubtedly will be developed as more is learned about
HIV infection and the opportunities for intervention expand, but this
book should remain a valuable reference source for years to come.
Walter R. Dowdle
Deputy Director
Centers for Disease Control
Contents
Foreword by Walter R. Dowdle v
Contributors IX
l. Testing for AIDS and Other Human Retroviruses:
An Overview 1
Gerald Schochetman
2. Testing for Retroviral Infections: Medical Indications and
Ethical Considerations 6
John Ward
3. Biology of Human Immunodeficiency Viruses 18
Gerald Schochetman
4. Immunologic Aspects of Human Immunodeficiency Virus
Infection 30
Alison C. Mawle and J. Steven McDougal
5. Serologic Tests for the Detection of Human Immunodeficiency
Virus Infection 48
J. Richard George and Gerald Schochetman
6. Quality Control for Serologic Testing 79
J. Richard George
7. Direct Detection of Human Immunodeficiency Virus Infection
Using the Polymerase Chain Reaction 90
Gerald Schochetman and John J. Sninsky
8. Human Immunodeficiency Virus Culture 111
Mark A. Rayfield
9. Use of Flow Cytometry to Monitor Human Immunodeficiency
Virus Disease 123
Alan L. Landay and Betsy M. Ohlsson-Wilhelm
vii
viii Contents
10. Prognostic Indicators for Progression of Human
Immunodeficiency Virus Disease 143
C. Robert Horsburgh
11. Human Immunodeficiency Virus Infection in Children 152
Martha Rogers and Gerald Schochetman
12. Other Human Retrovirus Infections: HTLV-I and HTLV-II 168
Michael D. Lairmore and Renu Lal
13. Biosafety: Principles and Practices in the Human
Immunodeficincy Virus Laboratory 189
M. E. Kennedy
14. Management of Occupational Exposure to the Human
Immunodeficiency Virus 197
Kenneth G. Castro and Jacquelyn A. Polder
Glossary 205
Subject Index 213
Contributors
Kenneth G. Castro, M.D., Epidemiology Branch, Division of HIVI
AIDS, National Center for Infectious Diseases, Centers for Disease
Control, Atlanta, GA 30333
J. Richard George, Ph.D., Chief, Developmental Technology Section,
Laboratory Investigations Branch, Division of HIV/AIDS, National
Center for Infectious Diseases, Centers for Disease Control, Atlanta,
GA 30333
C. Robert Horsburgh, Jr. M.D., Epidemiology Branch, Division of
HIV I AIDS, National Center for Infectious Diseases, Centers for Disease
Control, Atlanta, GA 30333
M.E. Kennedy, Chief, Office of Biosafety, Laboratory Center for
Disease Control, Health and Welfare Canada, Tunney's Pasture,
Ottawa, Ontario, Canada, KIA OL2
Michael D. Lairmore, D.V.M., Ph.D., Department of Veterinary
Pathobiology, The Ohio State University, Columbus, OH 43210
Renu Lal, Ph.D., Retrovirus Diseases Branch, Division of Viral and
Rickettsial Diseases, National Center for Infectious Diseases, Centers for
Disease Control, Atlanta, GA 30333
Alan L. Landay, Ph.D., Director, Immunology Laboratory, Office of
Consolidated Laboratory Services, Rush-Presbyterian-St. Luke's Medical
Center, Chicago, IL 60612
Alison C. Mawle, Ph.D., Division of HIV/AIDS, National Center for
Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333
ix
x Contributors
J. Steven McDougal, M.D., Chief, Immunology Branch, Division of
HIV I AIDS, National Center for Infectious Diseases, Centers for Disease
Control, Atlanta, GA 30333
Betsy M. Ohlsson-Wilhelm, Ph.D., Departments of Medicine and
Microbiology and Immunology, The Pennsylvania State University,
College of Medicine, Hershey, P A 17033
Jacquelyn A. Polder, B.S.N., M.P.H., AIDS Activity, Hospital
Infections Program, National Center for Infectious Diseases, Centers for
Disease Control, Atlanta, GA 30333
Mark A. Rayfield, Ph.D., Chief, Cell Biology Section, Laboratory
Investigations Branch, Division of HIV/AIDS, National Center for
Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333
Martha F. Rogers, M.D., Chief, Epidemiology Branch, Division of
HIV/AIDS, National Center for Infectious Diseases, Centers for Disease
Control, Atlanta, GA 30333
Gerald Schochetman, Ph.D., Chief, Laboratory Investigations Branch,
Division of HIV/AIDS, National Center for Infectious Diseases, Centers
for Disease Control, Atlanta, GA 30333
John J. Sninsky, Ph.D., PCR Division, Cetus Corp., Emoryville, CA
94608
John W. Ward, M.D., Chief, Reporting and Analysis Section,
Surveillance Branch, Division of HIV/AIDS, National Center for
Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333
1
Testing for AIDS and Human
Retroviruses: An Overview
GERALD SCHOCHETMAN
Since the first cases of acquired imunodeficiency syndrome (AIDS) were
described in 1981, the global impact of this new epidemic has been
dramatic. By December 1990, more than 150 countries had reported
over 307,000 cases to the World Health Organization (WHO), and
over 8 million persons worldwide were estimated to be infected with
the human immunodeficiency virus type 1 (HIV-1), the etiologic agent
of AIDS. There are estimated to be at least 1 million HI V-infected
persons in the United States alone. Most of these infected persons are
expected to develop AIDS. HIV infection throughout the world has
continued to be limited to four major modes of transmission: (i) sexual
intercourse (vaginal or anal); (ii) transfusion of HIV-contaminated
blood or blood products; (iii) sharing of contaminated injection equip
ment (mainly involved in illegal intravenous drug use); and (iv) trans
mission from an infected woman to her fetus or infant (perinatal
transmission) .
HIV-1 was discovered in 1983-1984 and subsequently characterized
and shown to belong to a group of viruses known as the lentiviruses,
which are a subgroup of the retrovirus family of viruses. It was observed
early in the AIDs epidemic that the T4-helper lymphocyte showed a
dramatic decline in infected patients. It was subsequently shown that the
T4 cells were the principal target of HIV- 1 and that their loss was caused
by their preferential infection and destruction by the virus. The preferen
tial infection of T4 cells by HIV-1 resulted from the presence of the CD4
protein on the surface of these cells. It was later discovered that mono
cytes and macrophages, which also express the CD4 protein, could also
be infected and become functionally compromised.
Because HIV- 1 can integrate its genetic information into the chromo
somes of the infected cells, it can remain for the life of the infected cell.
The virus can remain in the cell in a quiescent or latent state, or it can
become activated through mechanisms as yet unclear, leading to produc
tion and spread of the virus. The viral genetic information (in the form of
DNA) can replicate with the host's cellular DNA, yielding HIV-infected
