TY - JOUR
T1 - Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease
AU - Chou, Sunwen
AU - Marousek, Gail
AU - Guentzel, Susan
AU - Follansbee, Stephen E.
AU - Poscher, Margaret E.
AU - Lalezari, Jacob P.
AU - Miner, Richard C.
AU - Drew, W. Lawrence
N1 - Funding Information:
Received 26 February 1997; revised 24 April 1997. Financial support: Department of Veterans Affairs research funds; NIH (AI-39938). Reprints or correspondence: Dr. Sunwen Chou, VA Medical Center 111F, 3710 SW US Veterans Hospital Rd., Portland OR 97201.
PY - 1997
Y1 - 1997
N2 - In a human immunodeficiency virus-infected subject cytomegalovirus (CMV) isolated 9 months after the patient began oral ganciclovir prophylaxis was resistant to ganciclovir and cidofovir and contained mutations in both UL97 and Pol coding regions. At 1 year, retinitis developed, which progressed despite intravenous ganciclovir followed by foscarnet and then cidofovir. A subsequent buffy coat virus isolate was resistant to all three drugs and contained new mutations in UL97 and Pol. By individually transferring the observed mutations to laboratory strain AD169, it was shown that a mutation at codon 603 of UL97 conferred resistance to ganciclovir, a mutation at codon 412 of Pol conferred resistance to both ganciclovir and cidofovir, and a mutation at codon 802 of Pol conferred resistance to ganciclovir and foscarnet. This case illustrates the development of multidrug resistance during prolonged exposure to antiviral therapy for CMV and cross-resistance arising from point mutations in the CMV Pol gene.
AB - In a human immunodeficiency virus-infected subject cytomegalovirus (CMV) isolated 9 months after the patient began oral ganciclovir prophylaxis was resistant to ganciclovir and cidofovir and contained mutations in both UL97 and Pol coding regions. At 1 year, retinitis developed, which progressed despite intravenous ganciclovir followed by foscarnet and then cidofovir. A subsequent buffy coat virus isolate was resistant to all three drugs and contained new mutations in UL97 and Pol. By individually transferring the observed mutations to laboratory strain AD169, it was shown that a mutation at codon 603 of UL97 conferred resistance to ganciclovir, a mutation at codon 412 of Pol conferred resistance to both ganciclovir and cidofovir, and a mutation at codon 802 of Pol conferred resistance to ganciclovir and foscarnet. This case illustrates the development of multidrug resistance during prolonged exposure to antiviral therapy for CMV and cross-resistance arising from point mutations in the CMV Pol gene.
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U2 - 10.1086/517302
DO - 10.1086/517302
M3 - Article
C2 - 9291334
AN - SCOPUS:0030788134
SN - 0022-1899
VL - 176
SP - 786
EP - 789
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -