Clinical Use of Antiviral Drugs

419 Pages·1988·14.47 MB·English

by  B. E. Juel-Jensen (auth.)

CLINICAL USE OF ANTIVIRAL DRUGS
Yechiel Becker, Series Editor
Julia Hadar, Managing Editor
DEVELOPMENTS IN VETERINARY VIROLOGY
Payne, L.N. (ed.) Marek's Disease (1985)
Burny, A. and Mammerickx, M. (eds.) Enzootic Bovine Leukosis and
Bovine Leukemia Virus (1987)
Becker, Y. (ed.) African Swine Fever (1987)
DeBoer, G.F. (ed.) Avian Leukosis (1987)
Liess, B. (ed.) Classical Swine Fever and Related Viral Infections (1987)
Darai, G. (ed.) Virus Diseases in Laboratory and Captive Animals
(1988)
DEVELOPMENTS IN MOLECULAR VIROLOGY
Becker, Y. (ed.) Herpesvirus DNA (1981)
Becker, Y. (ed.) Replication of Viral and Cellular Genomes (1983)
Becker, Y. (ed.) Antiviral Drugs and Interferon: The Molecular Basis
of Their Activity (1983)
Kohn, A. and Fuchs, P. (eds.) Mechanisms of Viral Pathogenesis from
Gene to Pathogen (1983)
Becker, Y. (ed.) Recombinant DNA Research and Viruses, Cloning and
Expression of Viral Genes (1985)
Feitelson, M. Molecular Components of Hepatitis B Virus (1985)
Becker, Y. (ed.) Viral Messenger RNA: Transcription, Processing,
Splicing and Molecular Structure (1985)
Doerfler, W. (ed.) Adenovirus DNA: The Viral Genome and Its
Expression (1986)
Aloni, Y. (ed.) Molecular Aspects of Papovaviruses (1987)
DEVELOPMENTS IN MEDICAL VIROLOGY
Levine, P .H. (ed.) Epstein-Barr Virus and Associated Diseases (1985)
Becker, Y. (ed.) Virus Infections and Diabetes Mellitus (1987)
DeClercq, E. (ed.) Clinical Use of Antiviral Drugs (1988)
CLINICAL USE OF ANTIVIRAL DRUGS
Edited by
Professor Dr. Erik De Clercq
Rega Institute for Medical Research
Katholieke Universiteit Leuven
~.
"
Martinus Nijboff Publishing
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Library of Congress Cataloging-in-Publication Data
Clinical use of antiviral drugs I edited by Erik De Clercq.
p. cm. - (Developments in medical virology)
Includes bibliographies and index.
ISBN-\3: 978-1-4612-8966-1 e-ISBN-13: 978-14613-1715-9
DOl: 10.10071978-1-4613-1715-9
1. Antiviral agents. 2. Virus diseases-Chemotherapy. I. De
Clercq, Erik. II. Series.
[DNLM: 1. Antiviral Agents-therapeutic use. 2. Virus Diseases
drug therapy. QV 268.S C641)
RM411.CS7 1988
616.9'2S061-dcI9
DNLM/DLC 87-314OS
for Library of Congress CIP
Copyright © 1988 by Martinus Nijhoff Publishing, Boston
Softcover reprint of the hardcover 1s t edition 1988
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise,
without the prior written permission of the publisher, Martinus Nijhoff Publishing, 101 Philip Drive,
Assinippi Park, Norwell, Massachusetts 02061.
CONTENTS
1
Clinical Use of Antiviral Drugs
B.E. Juel-Jensen 1
2
Idoxuridine or How It All Began
W.H. Prusoff 15
3
The Treatment of Herpetic Eye Infections with Trifluridine and
Other Antivirals
H.E. Kaufman 25
4
Treatment (Bromovinyldeoxyuridine) of Herpetic Eye Infections
P.C. Maudgal and E. De Clercq 39
5
Diagnosis and Treatment of Herpes Simplex Encephalitis
R.J. Whitley 49
6
Treatment of Herpes Simplex Labialis
S.L. Spruance 67
7
Treatment of Herpes Genitalis
S.L. Sacks 87
8
Treatment of Herpes Simplex Virus Infections in
Immunosuppressed Patients
R. Saral and P. Lietman 115
9
Antiviral Therapy of Varicella-Zoster Virus Infections
J. Englund and H.H. Balfour, Jr. 127
10
Treatment (Bromovinyldeoxyuridine) of Varicella-Zoster
Virus Infections
S. Shigeta and E. De Clercq 145
11
Therapy and Prevention of Cytomegalovirus Infections
P.R. Skolnik and M.S. Hirsch 159
12
The Prophylaxis of Herpes Group Infections in Patients with
Haematological Malignancy
H.G. Prentice and I.M. Hann 195
vi
13
Resistance of Herpes Viruses to Nucleoside Analogues-
Mechanisms and Clinical Importance
C. Crumpacker 207
14
Clinical Use of Foscarnet (Phosphonoformate)
B. Oberg, S. Behrnetz, B. Eriksson, H. Jozwiak, A. Larsson,
J.O. Lernestedt and V. Lindso Aberg 223
15
Prophylaxis and Treatment of Rhinovirus Infections
D.A.J. Tyrell and W. Al-Nakib 241
16
Rimantadine and Amantadine in the Prophylaxis and Therapy
of Influenza A
R. Dolin 277
17
Ribavirin Aerosol Treatment of Influenza, Respiratory Syncytial
and Parainfluenza Virus Infections of Man
V. Knight and B.E. Gilbert 289
18
Antiviral Therapy of Highly Pathogenic Viral Diseases
J.B. McCormick and S.P. Fisher-Hoch 305
19
Perspectives in the Use of Antiviral Agents for Prevention and
Treatment of Respiratory Virus Infections
S.J. Sperber and F.G. Hayden 317
20
Perspectives for the Treatment of Gastrointestinal Tract Virus
Infections
L.A. Babiuk, M.1. Sabara and P. Frenchick 341
21
Principles of Antiretroviral Therapy for AIDS and
Related Diseases
J. Balzarini and S. Broder 361
22
Promises to Keep: Clinical Use of Antiviral Drugs
G.J. Galasso 387
Index 405
CONTRIBUTING AUTHORS
1. DR. B.E. JUEL-JENSEN 5. DR. R.J. WHITLEY
Nuffield Department of Clinical Department of Pediatrics and
Medicine Microbiology
Radcliffe Infirmary Room 609 COLD
University of Oxford School of Medicine
Oxford OX2 6HE, United Kingdom The University of Alabama
Birmingham, Alabama 35294
2. DR. W.H. PRUSOFF U.S.A.
Department of Pharmacology
Sterling Hall of Medicine 6. DR. S.L. SPRUANCE
Yale University School of Medicine Division of Infectious Diseases
333 Cedar Street Department of Medicine
P.O. Box 3333 University of Utah School of
New Haven, Connecticut 06510 Medicine
U.S.A. Salt Lake City, Utah 84132
U.S.A.
3. DR. H.E. KAUFMAN The Centre International de Re-
Lions Eye Research Laboratories cherches Dermatologiques (CIRD)
LSU Eye Center Sophia Antipolis
Louisiana State University Medical 06565 Valbonne, France
Center School of Medicine
New Orleans, Louisiana 70112 7. DR. S.L. SACKS
U.S.A. Division of Infectious Diseases
Department of Medicine
4. DR. P .C. MAUDGAL Health Sciences Centre Hospital
Eye Research Laboratory The University of British Columbia
Ophthalmological Clinic 2211 Wesbrook Mall
Academic Hospital St. Rafael Vancouver, British Columbia
Katholieke Universiteit Leuven Canada V6T lW5
Kapucijnenvoer, 7
B-3000 Leuven, Belgium 8. DR. R. SARAL
Department of Ophthalmology Department of Oncology
Academic Hospital Free University The Johns Hopkins University
Postbus 7057 School of Medicine
1007 MB Amsterdam Baltimore, Maryland 21205, U.S.A.
The Netherlands
DR. P. LIETMAN
DR. E. DE CLERCQ Division of Clinical Pharmacology
Rega Institute for Medical Research The Johns Hopkins University
Katholieke Universiteit Leuven School of Medicine
Minderbroedersstraat 10 Baltimore, Maryland 21205, U.S.A.
B-3000 Leuven, Belgium
vii
viii
9. DR. J. ENGLUND 13. DR. C. CRUMPACKER
Department of Pediatrics Division of Infectious Diseases
Laboratory Medicine and Pathology Beth Israel Hospital
University of Minnesota Medical Harvard Medical School
School 330 Brookline Avenue
Minneapolis, Minnesota 55455 Boston, Massachusetts 02215
U.S.A. U.S.A.
DR. H.H. BALFOUR, Jr. 14. DR.B.OBERG
Department of Pediatrics Department of Antiviral
Laboratory Medicine and Pathology Chemotherapy
University of Minnesota Medical Astra Alab AB
School S-15185 Sbdertiilje, Sweden
Minneapolis, Minnesota 55455
U.S.A. DR. S. BEHRNETZ
Department of Clinical Research
10. DR. S. SHIGETA Astra Alab AB
Department of Bacteriology S-15185 S6dertiilje, Sweden
Fukushima Medical College
Fukushima 960, Japan DR. B. ERIKSSON
Department of Clinical Research
DR. E. DE CLERCQ Astra Alab AB
Rega Institute for Medical Research S-15185 Sddertalje, Sweden
Katholieke Universiteit Leuven
Minderbroedersstraat 10 DR. H. JOZWIAK
B-3000 Leuven, Belgium Department of Clinical Research
Astra Alab AB
11. DR. P.R. SKOLNIK S-15185 Sodertiilje, Sweden
Infectious Disease Unit
Department of Medicine DR. J.O. LERNESTEDT
Massachusetts General Hospital Department of Clinical Research
Boston, Massachusetts 02114 Astra Alab AB
U.S.A. S-15185 Sodertiilje, Sweden
DR. M.S. HIRSCH DR. V. LINDSO ABERG
Infectious Disease Unit Department of Clinical Research
Department of Medicine Astra Alab AB
Massachusetts General Hospital S-15185 Sodertalje, Sweden
Boston, Massachusetts 02114
U.S.A. 15. DR. D.A.J. TYRRELL
MRC Common Cold Unit
12. DR. H.G. PRENTICE Harvard Hospital
Department of Haematology Coombe Road
The Royal Free Hospital Salisbury, Wilts SP2 8BW
Pond Street United Kingdom
Hampstead, London NW3 2QG
United Kingdom DR. W. AL-NAKIB
MRC Common Cold Unit
DR. I.M. HANN Harvard Hospital
Royal Hospital for Sick Children Coombe Road
Glasgow, United Kingdom Salisbury, Wilts SP2 8BW
United Kingdom
ix
16. DR. R. DOLIN 20. DR. L.A. BABIUK
Infectious Disease Unit Veterinary Infectious Disease
School of Medicine Organization
University of Rochester 124 Veterinary Road
601 Elmwood Avenue Saskatoon, Saskatchewan S7N
Rochester, New York 14642, U.S.A. OWO, Canada
17. DR. V. KNIGHT DR. M.1. SABARA
Department of Microbiology and Veterinary Infectious Disease
Immunology Organization
Baylor College of Medicine 124 Veterinary Road
Texas Medical Center Saskatoon, Saskatchewan S7N
One Baylor Plaza OWO, Canada
Houston, Texas 77030, U.S.A.
DR. P. FRENCHICK
DR. B.E. GILBERT Veterinary Infectious Disease
Department of Microbiology and Organization
Immunology 124 Veterinary Road
Baylor College of Medicine Saskatoon, Saskatchewan S7N
Texas Medical Center OWO, Canada
One Baylor Plaza
Houston, Texas 77030, U.S.A. 21. DR. J. BALZARINI
Rega Institute for Medical Research
18. DR. J.B. McCORMICK Katholieke Universiteit Leuven
Special Pathogens Branch Minderbroedersstraat 10
Division of Viral Diseases B-3ooo Leuven, Belgium
Center for Infectious Diseases
Centers for Disease Control DR. S. BRODER
Atlanta, Georgia 30333, U.S.A. Clinical Oncology Program
National Cancer Institute
DR. S.P. FISHER-HOCH National Institutes of Health
Special Pathogens Branch Bethesda, Maryland 20892, U.S.A.
Division of Viral Diseases
Center for Infectious Diseases 22. DR. G.J. GALASSO
Centers for Disease Control Office of the Director
Atlanta, Georgia 30333, U.S.A. National Institutes of Health
Bethesda, Maryland 20892, U.S.A.
19. DR. S.J. SPERBER
Departments of Internal Medicine
and Pathology
University of Virginia School of
Medicine
Charlottesville, Virginia 22908
U.S.A.
DR. F.G. HAYDEN
Departments of Internal Medicine
and Pathology
University of Virginia School of
Medicine
Charlottesville, Virginia 22908
U.S.A.
PREFACE
Antiviral chemotherapy has come of age, and, after an initial slow pro
gress, the development of new antiviral agents has proceeded at a more rapid
pace and the perspectives for their clinical use have increased considerably.
Now, 25 years after the first antiviral assay (idoxuridine) was introduced in
the clinic, it is fitting to commemorate the beginning of the antivirals' era.
In its introductory chapter B.E. Juel-Jensen touches on what may be con
sidered as five of the most fundamental requirements of an antiviral drug :
efficacy, relative non-toxicity, easy solubility, ready availability and rea
sonable cost. Surely, the antiviral drugs that have so far been used in the
clinic could still be improved upon as one or more of these five essential
demands are concerned.
How is all began is narrated by W.H. Prusoff. The first antiviral drugs
to be used in humans were methisazone and idoxuridine, the former, which is
now of archival interest, in the prevention of smallpox, the latter, which was
approved for clinical use in the United States in 1962, for the topical
treatment of herpetic keratitis.
In terms of potency, also because of solubility reasons, idoxuridine has
been superseded by trifluridine in the topical treatment of herpes simplex
epithelial keratitis. H.E. Kaufman did not find trifluridine or acyclovir ef
fective in the treatment of deep stromal keratitis or iritis and he reckons
that other antiviral drugs (i.e. bromovinyldeoxyuridine) would not be effec
tive either.
However, P.C. Maudgal and E. De Clercq found that stromal keratitis reac
ted favorably to topical treatment with bromovinyldeoxyuridine, and so did pa
tients with dendritic and geographic corneal ulcers. Even those patients whose
keratitis did not respond to treatment with either idoxuridine, trifluridine,
vidarabine or acyclovir healed promptly when treatment was switched to bromo
vinyldeoxyuridine. Preliminary findings indicate that combined oral and topi
cal bromovinyldeoxyuridine treatment is also efficacious against ophthalmic
herpes zoster.
Herpes simplex encephalitis has, because of its severity (mortality in
excess of 70 %), since the 1960's been considered as an important target di
sease for antivirals. Acyclovir is currently the drug of choice for the treat
ment of biopsy-proven herpes simplex encephalitis, but, as pointed out by R.J.
Whitley, therapeutic benefit depends on the age of the patient, the level of
consciousness (Glasgow coma score) and the onset of treatment relative to the
onset of the disease. Further improvements in therapeutic regimens as well as
non-invasive diagnostic procedures are highly desirable.
The development and evaluation of an effective chemotherapy for recurrent
herpes simplex labialis in otherwise normal, non-immunocompromised subject has
proven to be an arduous task, and S.L. Spruance explains why the treatment of
herpes labialis has remained elusive. Clinical benefit may be achieved, how
ever, by improved means of drug delivery and treatment initiated in the ear
liest lesion stages.
xi