Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.
Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with acquired immunodeficiency syndrome. In a prospective study of 210 patients with CMV retinitis, 26 were identified as having either a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC(50) >6.0 microm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC(50) >8.0 microM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC(50) >8.0 microM appeared to be better at identifying genotypic resistance. UL97 mutations identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High-level ganciclovir resistance (IC(50), >30 microM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.
Jabs
D A
DA
Departments of Ophthalmology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. djabs@jhmi.edu
Martin
B K
BK
Forman
M S
MS
Dunn
J P
JP
Davis
J L
JL
Weinberg
D V
DV
Biron
K K
KK
Baldanti
F
F
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D001769:Blood / Q000821:virology; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017726:Cytomegalovirus Retinitis / Q000821:virology*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011446:Prospective Studies; D014556:Urine / Q000821:virology; D014764:Viral Proteins
D000998:Antiviral Agents; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase; D015774:Ganciclovir