Mutations Conferring Ganciclovir Resistance in a Cohort of Patients with Acquired Immunodeficiency Syndrome and Cytomegalovirus Retinitis

• Published in: The Journal of infectious diseases 2001-01, Vol.183 (2), p.333-337
• Main Authors: Jabs, Douglas A., Martin, Barbara K., Forman, Michael S., Dunn, J. P., Davis, Janet L., Weinberg, David V., Biron, Karen K., Baldanti, Fausto
• Format: Article
• Language: English
• Subjects: Adult; Aged; AIDS; AIDS-Related Opportunistic Infections - virology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antivirals; Biological and medical sciences; Blood; Blood - virology; Cohort Studies; Concise Communications; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus - isolation & purification; Cytomegalovirus retinitis; Cytomegalovirus Retinitis - virology; DNA-Directed DNA Polymerase - genetics; Drug Resistance, Microbial - genetics; Female; Ganciclovir - pharmacology; Genetic mutation; Genotype; Human cytomegalovirus; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Laboratory schools; Male; Medical sciences; Middle Aged; Mutation; Pharmacology. Drug treatments; Phenotype; Phosphotransferases (Alcohol Group Acceptor) - genetics; Prospective Studies; Retinitis; Urine; Urine - virology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Proteins; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/317931

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 IC50 >6.0 µm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC50 >8.0 µM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC50 >8.0 µM 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 (IC50, >30 µM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.