DOUBLE RESISTANCE TO GANCICLOVIR AND FOSCARNET OF 4 HUMAN CYTOMEGALOVIRUS STRAINS RECOVERED FROM AIDS PATIENTS

Four human cytomegalovirus (HCMV) isolates from four different AIDS pa tients treated with both ganciclovir and foscarnet and not responding clinically to antiviral treatment, were studied in order to verify the occurrence of double resista nce to both drugs, and to define whether single or multiple HCMV strains could be responsible for the double r esistance. Peripheral blood leukocytes (PBL), the relevant conventiona l viral isolates, and plaque-purified strains from all four patients w ere examined by antiviral drug susceptibility testing by an immediate- early antigen plaque reduction assay and by restriction fragment lengt h polymorphism (RFLP) analysis using polymerase chain reaction (PCR)-a mplified multiple genome regions and endonucleases. All four HCMV stra ins had a high level of resistance to both ganciclovir and foscarnet. A single HCMV strain was shown to be responsible for the dual resistan ce in each patient. HCMV strain identity and uniqueness were shown for each of the four patients in blood samples, viral isolates, and plaqu e-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 recovere d from blood of AIDS patients represents an emerging problem. Although it is known that multiple HCMV strains may cocirculate in the blood o f AIDS patients, single strains appear to be responsible for the dual resistance. Molecular mechanisms responsible for the double resistance the four reported strains are under study. (C) 1995 Wiley-Liss, Inc.