       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).

