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.
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.
Gerna
Giuseppe
G
Servizio di Virologia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy. g.gerna@smatteo.pv.it.
Sarasini
Antonella
A
Lilleri
Daniele
D
Percivalle
Elena
E
Torsellini
Maria
M
Baldanti
Fausto
F
Revello
M Grazia
MG
D000956:Antigens, Viral / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral; D042783:Endothelial Cells / Q000821:virology; D015774:Ganciclovir / Q000627:therapeutic use*; D006801:Humans; D009504:Neutrophils; D016377:Organ Transplantation; D010750:Phosphoproteins / Q000097:blood*; D014763:Viral Matrix Proteins / Q000097:blood*
D000956:Antigens, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D015774:Ganciclovir