TY - JOUR
T1 - Double resistance to ganciclovir and foscarnet of four human cytomegalovirus strains recovered from AIDS patients
AU - Sarasini, A.
AU - Baldanti, F.
AU - Furione, M.
AU - Percivalle, E.
AU - Brerra, R.
AU - Barbi, M.
AU - Gerna, G.
PY - 1995
Y1 - 1995
N2 - Four human cytomegalovirus (HCMV) isolates from four different AIDS patients treated with both gancic[ovir 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.
AB - Four human cytomegalovirus (HCMV) isolates from four different AIDS patients treated with both gancic[ovir 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.
KW - AIDS
KW - Drug resistance
KW - Foscarnet
KW - Ganciclovir
KW - HCMV
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U2 - 10.1002/jmv.1890470309
DO - 10.1002/jmv.1890470309
M3 - Article
C2 - 8551275
AN - SCOPUS:0028820260
VL - 47
SP - 237
EP - 244
JO - Journal of Medical Virology
JF - Journal of Medical Virology
SN - 0146-6615
IS - 3
ER -