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1996-03-04
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Document 0670
DOCN M9640670
TI Double resistance to ganciclovir and foscarnet of four human
cytomegalovirus strains recovered from AIDS patients.
DT 9604
AU Sarasini A; Baldanti F; Furione M; Percivalle E; Brerra R; Barbi M;
Gerna G; Viral Diagnostic Service, University of Pavia, Istituto di;
Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo,; Italy.
SO J Med Virol. 1995 Nov;47(3):237-44. Unique Identifier : AIDSLINE
MED/96129551
AB Four human cytomegalovirus (HCMV) isolates from four different AIDS
patients treated with both ganciclovir and foscarnet and not responding
clinically to antiviral treatment, were studied in order to verify the
occurrence of double resistance to both drugs, and to define whether
single or multiple HCMV strains could be responsible for the double
resistance. Peripheral blood leukocytes (PBL), the relevant conventional
viral isolates, and plaque-purified strains from all four patients were
examined by antiviral drug susceptibility testing by an immediate-early
antigen plaque reduction assay and by restriction fragment length
polymorphism (RFLP) analysis using polymerase chain reaction
(PCR)-amplified multiple genome regions and endonucleases. All four HCMV
strains had a high level of resistance to both ganciclovir and
foscarnet. A single HCMV strain was shown to be responsible for the dual
resistance in each patient. HCMV strain identity and uniqueness were
shown for each of the four patients in blood samples, viral isolates,
and plaque-purified strains. In addition, in two patients the same
single HCMV strain shifted progressively from drug sensitivity to
ganciclovir and then to ganciclovir-foscarnet resistance. These findings
document that resistance to both ganciclovir and foscarnet of HCMV
strains recovered from blood of AIDS patients represents an emerging
problem. Although it is known that multiple HCMV strains may cocirculate
in the blood of AIDS patients, single strains appear to be responsible
for the dual resistance. Molecular mechanisms responsible for the double
resistance of the four reported strains are under study.
DE Adult Antiviral Agents/*PHARMACOLOGY AIDS-Related Opportunistic
Infections/*VIROLOGY Case Report Cell Line Cytomegalovirus/*DRUG
EFFECTS/ISOLATION & PURIF Cytomegalovirus
Infections/COMPLICATIONS/*VIROLOGY Drug Resistance, Microbial Drug
Resistance, Multiple Female Foscarnet/*PHARMACOLOGY
Ganciclovir/*PHARMACOLOGY Human Male Plaque Assay Reverse
Transcriptase Inhibitors/*PHARMACOLOGY Support, Non-U.S. Gov't Time
Factors JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).