AIDS Epidemiology - A Quantitative Approach - R. Brookmeyer, M. Gail (Oxford, 1994) WW

371 Pages·1994·19.5 MB·English

AIDS Epidemiology: A Quantitative Approach

Monographs in Epidemiology and Biostatistics
edited by Jennifer L. Kelsey, Michael G. Marmot, Paul D. Stolley, Martin P. Vessey

1
THE EPIDEMIOLOGY
OF DEMENTIA
James A. Mortimer and Leonard M.
Schuman 1981

2
CASE-CONTROL STUDIES
Design, Conduct, Analysis
James J. Schlesselman 1982

3
EPIDEMIOLOGY
OF MUSCULOSKELETAL
DISORDERS
Jennifer L. Kelsey 1982

4
URBANIZATION
AND CANCER MORTALITY
The United States Experience,
1950—1975
Michael R. Greenberg 1983
5
AN INTRODUCTION
TO EPIDEMIOLOGIC
METHODS
Harold A. Kahn 1983

6
THE LEUKEMIAS
Epidemiologic Aspects
Martha S. Linet 1984

7
SCREENING IN CHRONIC
DISEASE
Alan S. Morrison 1985
8
CLINICAL TRIALS
Design, Conduct, and Analysis
Curtis L. Meinert 1986
9
VACCINATING AGAINST
BRAIN DYSFUNCTION
SYNDROME
The Campaign Against Rubella
and Measles
Ernest M. Gruenberg 1986

10 METHODS IN
OBSERVATIONAL
EPIDEMIOLOGY
Jennifer L. Kelsey, W. Douglas
Thompson, Alfred S. Evans
1986

11 CLINICAL
EPIDEMIOLOGY:
THE STUDY OF
THE OUTCOME OF ILLNESS
Noel S. Weiss 1986

12 STATISTICAL METHODS
IN EPIDEMIOLOGY
Harold A. Kahn and Christopher T.
Sempos 1989
13 RESEARCH METHODS
IN OCCUPATIONAL
EPIDEMIOLOGY
Harvey Checkoway, Neil E. Pearce,
Douglas J. Crawford-Brown 1989
14 CONCEPTION TO BIRTH
Epidemiology of Prenatal Development
Jennie Kline, Zena Stein, Mervyn
Susser 1989
15
NUTRITIONAL
EPIDEMIOLOGY
Walter Willett 1990
16 STATISTICAL MODELS
FOR LONGITUDINAL
STUDIES OF HEALTH
James H. Dwyer, Manning Feinleib,
Peter Lippert, Hans Hoffmeister
1991
17
STATISTICAL ANALYSIS
OF EPIDEMIOLOGIC DATA
Steve Selvin 1991
18 THE DRUG ETIOLOGY
OF AGRANULOCYTOSIS
AND APLASTIC ANEMIA
David W. Kaufman, Judith P. Kelly,
Micha Levy, Samuel Shapiro 1991
19 SCREENING IN CHRONIC
DISEASE, Second edition
Alan S. Morrison 1992
20 EPIDEMIOLOGY
AND CONTROL OF NEURAL
TUBE DEFECTS
J. Mark Elwood, Julian Little,
J. Harold Elwood 1992
21
PRINCIPLES OF
EXPOSURE MEASUREMENT
IN EPIDEMIOLOGY
Bruce K. Armstrong, Emily White,
Rodolfo Saracci 1992
22 AIDS EPIDEMIOLOGY:
A QUANTITATIVE
APPROACH
Ron Brookmeyer and Mitchell H.
Gail 1994

AIDS Epidemiology:
A Quantitative Approach

Ron Brookmeyer
Department of Biostatistics
School of Hygiene and Public Health
Johns Hopkins University

Mitchell H. Gail
Epidemiology and Biostatistics Program
National Cancer Institute

New York Oxford
OXFORD UNIVERSITY PRESS
1994

Oxford University Press

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Copyright © 1994 by Oxford University Press, Inc.

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All rights reserved. No part of this publication may be reproduced,
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Library of Congress Cataloging-in-Publication Data
Brookmeyer, Ron.
AIDS epidemiology : a quantitative approach / Ron Brookmeyer
and Mitchell H. Gail.
p. cm. Includes bibliographical references and index.
ISBN 0-19-507641-9
1. AIDS (Disease)—Epidemiology. 2. Biometry.
3. Epidemiology—Statistical methods. I. Gail, Mitchell H. II. Title.
[DNLM:
1. Acquired Immunodeficiency Syndrome—epidemiology.
2. Epidemiologic Methods. WD 308 B872a 1993]
RA644.A25B75 1994
614.5'993—dc20
DNLM/DLC
for Library of Congress
92-48337

9 8 7 6 5 4 3 2 1

Printed in the United States of America
on acid-free paper

To Robin and Claire (R. B.)

To my wonderful parents (M. G.)

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Preface

The purpose of this book is to review the contribution of statistical
science to our understanding of the acquired immunodeficiency syn-
drome (AIDS) and to summarize and interpret the major epidemiolog-
ical findings. Statistical ideas and approaches have contributed to an
understanding of factors that promote transmission of the human
immunodeficiency virus (HIV) and of strategies for preventing trans-
mission, to an accurate description of the natural history of disease
associated with HIV infection, including the "incubation" distribution
of the time from infection to the onset of AIDS, to the design and
analysis of therapeutic clinical trials and impending vaccine trials, and
to an assessment of the scope and likely course of the HIV epidemic and
of the incidence of AIDS. In some cases, non-standard statistical ideas
are absolutely crucial to avoid misleading interpretations of data,
because standard methods of analysis for chronic disease are not always
suitable for studying a rapidly growing epidemic and because non-
standard "samples of opportunity" can lead to severely biased results
unless the mode of sampling is taken into account.
Two examples illustrate these phenomena. If we plot the crude
numbers of incident AIDS cases reported to the Centers for Disease
Control (CDC) against calendar time, the most recent counts will be
misleadingly small because delays in reporting will reduce recent
counts. To avoid misleading interpretations of AIDS incidence data,
we must adjust for reporting delays. As a second example, the earliest
estimates of the incubation distribution of AIDS were obtained by
studying the incubation times of persons who developed AIDS as the
result of a contaminated blood transfusion. Because the available
cases in such a sample necessarily had relatively short incubation
times, a naive analysis of such data would tend to seriously under-
estimate the usual time it takes to develop AIDS.

viii
Preface

In other contexts, statistical thinking has helped define problems and
assess the extent and sources of uncertainty associated with given
conclusions. For example, the quality and type of information available
from a cohort of individuals whose dates of infection are unknown
("prevalent" cohorts) differ from that of a cohort whose dates of
seroconversion are known ("incident" cohorts). As another example,
estimates of the numbers of persons infected with HIV-1 in the United
States are obtained either from seroprevalence surveys in selected
populations or by "back-calculation" using AIDS incidence data and
information on the incubation distribution. Each of these methods is
subject to large random and systematic sources of error, yet the two
approaches are based on complementary types of information. In
making estimates of the numbers infected, it is essential to consider a
variety of sources of information and to report realistic assessments of
uncertainty.
It is our hope that this book will introduce epidemiologists to
statistical ideas that are helpful in analyzing and interpreting
epidemiologic and clinical data on AIDS. Likewise 'we hope to
introduce statisticians to some of the unusual features of epidemiologic
and clinical information on AIDS so that they may appreciate the need
for specialized statistical methods in this area. Finally, we hope some
readers will be interested in the story of data interpretation and
discovery in a rapidly evolving scientific context.

Topics Covered

We review the discovery of risk factors and the associated methodologic
difficulties of interpreting cohort and case-control data in a rapidly
evolving epidemic (Chapter 2). The statistical features of special
studies on the uninfected sexual partners of infected persons (partner
studies) are also reviewed and discussed (Chapter 2). Chapter 3
describes the results of surveys to estimate trends in HIV seroincidence
and seroprevalence. We also discuss the difficulties of interpreting data
from non-representative samples and of assessing the extent to which
general surveys are biased because persons at high risk of HIV infection
refuse to participate. We describe the special statistical approaches
used to estimate the incubation distribution and review available
results in Chapter 4. Age at infection is the only well documented factor
that influences the incubation distribution, but many markers, especi-
ally CD4+ T lymphocyte levels, have been used to monitor the
progression of HIV illness following infection. Chapter 5 describes
statistical issues that arise in interpreting information on cofactors that

Preface
ix

might influence the incubation distribution and on markers. We discuss
the reliability of assays to detect HIV infection and the effectiveness of
screening for HIV to protect the blood supply in Chapter 6. Chapter 7
outlines surveillance methods used to monitor AIDS incidence, includ-
ing methods for delay correction and extrapolation procedures. Back-
calculation procedures for estimating the infection curve from AIDS
incidence data and for projecting AIDS incidence are presented in
Chapter 8. Transmission models are developed to help understand
factors that influence the infection curve and to help define and
evaluate possible prevention strategies (Chapter 9). Chapter 10 stresses
the need to integrate a variety of sources of information in order to
understand epidemic trends and applies those ideas to studying trends
in underdeveloped countries, to forecasting in small geographic areas,
and to projecting pediatric AIDS. Statistical issues in vaccine develop-
ment and experimental therapeutics are described in Chapter 11.
Readers particularly interested in the natural history of HIV
infection in individuals may wish to concentrate on Chapters 1, 2, 4, 5,
6 and 11. Those interested in monitoring and forecasting the epidemic
in populations may wish to emphasize Chapters 1, 3, 6, 7, 8, 9 and 10.
Although this book is self-contained, there are a number of excellent
general sources for background information. AIDS: Etiology, Diagnosis,
Treatment and Prevention (edited by DeVita, Hellman and Rosenberg,
1988) and AIDS Pathogenesis and Treatment (edited by Levy) provide a
comprehensive introduction to biological and medical issues, and The
Epidemiology of AIDS (edited by Kaslow and Francis, 1989) describes
the epidemiology of specific risk groups. The three books, Confronting
AIDS: Directions for Public Health, Health Care and Research (Institute of
Medicine, 1986), Confronting AIDS: Update 1988 (Institute of Medicine,
1988) and The Second Decade (edited by Miller, Turner and Moses,
1990) document progress in scientific understanding and an evolution
of thinking on social, legal and ethical problems associated with the
AIDS epidemic. Jewell (1990) reviews statistical issues and innovative
statistical methods used to cope with AIDS data. The February, 1988
issue of Science includes papers on AIDS epidemiology in the United
States (Curran, Jaffe, Hardy, et al., 1988), international perspectives
(Piot, Plummer, Mhalu, et al., 1988), economic impact (Bloom and
Carliner, 1988), prevention (Fineberg, 1988) and other aspects.

Baltimore, Md.
R. B.
Rockville, Md.
M. G.
January 1993