In Vitro Model for the Study of the Dissociation of Increasing Antigenemia and Decreasing DNAemia and Viremia during Treatment of Human Cytomegalovirus Infection with Ganciclovir in Transplant Recipients

Research output: Contribution to journalArticle

Abstract

The paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case.

Original languageEnglish
Pages (from-to)1639-1647
Number of pages9
JournalJournal of Infectious Diseases
Volume188
Issue number11
DOIs
Publication statusPublished - Dec 1 2003

Fingerprint

Ganciclovir
Viremia
Cytomegalovirus Infections
Pharmaceutical Preparations
Foscarnet
Cytomegalovirus
Antiviral Agents
Neutrophils
Therapeutics
Endothelial Cells
In Vitro Techniques
Transplant Recipients

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

@article{e554dac67cfe42b58be079f80756aab1,
title = "In Vitro Model for the Study of the Dissociation of Increasing Antigenemia and Decreasing DNAemia and Viremia during Treatment of Human Cytomegalovirus Infection with Ganciclovir in Transplant Recipients",
abstract = "The paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90{\%}-99{\%} of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case.",
author = "Giuseppe Gerna and Antonella Sarasini and Daniele Lilleri and Elena Percivalle and Maria Torsellini and Fausto Baldanti and Revello, {M. Grazia}",
year = "2003",
month = "12",
day = "1",
doi = "10.1086/379376",
language = "English",
volume = "188",
pages = "1639--1647",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - In Vitro Model for the Study of the Dissociation of Increasing Antigenemia and Decreasing DNAemia and Viremia during Treatment of Human Cytomegalovirus Infection with Ganciclovir in Transplant Recipients

AU - Gerna, Giuseppe

AU - Sarasini, Antonella

AU - Lilleri, Daniele

AU - Percivalle, Elena

AU - Torsellini, Maria

AU - Baldanti, Fausto

AU - Revello, M. Grazia

PY - 2003/12/1

Y1 - 2003/12/1

N2 - The paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case.

AB - The paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case.

UR - http://www.scopus.com/inward/record.url?scp=0346256762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346256762&partnerID=8YFLogxK

U2 - 10.1086/379376

DO - 10.1086/379376

M3 - Article

C2 - 14639533

AN - SCOPUS:0346256762

VL - 188

SP - 1639

EP - 1647

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 11

ER -