Genotypic analysis of cytomegalovirus retinitis poorly responsive to intravenous ganciclovir but responsive to the ganciclovir implant☆☆☆
Accepted 1 May 2002.
Abstract
Purpose
To determine whether cytomegalovirus (CMV) retinitis that responded poorly to intravenous ganciclovir therapy but responded to the ganciclovir implant was caused by virus with resistance mutations in the viral UL97 and UL54 genes.
Design
Retrospective chart review and laboratory-based experimental study.
Methods
Regions of the CMV UL97 and UL54 were amplified from the vitreous and analyzed for resistant mutations by a combination of DNA sequencing and restriction digestion. Vitreous from patients with AIDS and retinal infections other than CMV retinitis served as negative controls.
Results
We amplified all target regions of UL97 DNA and most target regions of UL54 DNA from eight eyes with CMV retinitis. In one eye we found a ganciclovir resistance mutation at base 1781 of the UL97 gene, predicting an alanine to valine mutation at codon 594. In a second eye we found a ganciclovir resistance mutation at base 2960 of the UL54 gene, predicting an alanine to glycine mutation at codon 987. In two additional eyes, both from patients with bilateral retinitis, we found UL54 mutations that are likely to confer resistance to ganciclovir but have not been previously described. In both of these patients the UL54 genotype differed between the two diseased eyes.
Conclusions
Failure to control CMV retinitis with intravenous ganciclovir does not necessarily imply infection with a virus having a known mutation that confers drug resistance. The ganciclovir implant can be an effective therapy for CMV retinitis caused by virus with certain UL97 and UL54 resistance mutations. Cytomegalovirus UL54 genotypes can differ between eyes in patients with bilateral retinitis.
aFrancis I. Proctor Foundation and the Department of Ophthalmology (I.C.K., Y.I., C.S., T.P.M.), University of California San Francisco, San Francisco, California, USA
bDepartment of Ophthalmology (D.F.M.), Emory University School of Medicine, Atlanta, Georgia, USA
cDepartment of Ophthalmology (B.D.K.), University of California Irvine, Irvine, California, USA
Inquiries to Todd P. Margolis, MD, PhD, F. I. Proctor Foundation, 95 Kirkham, UCSF, San Francisco, CA 94143-0944, USA; fax: (415) 476-0527
☆ This study was supported in part by Research to Prevent Blindness, Inc., New York, New York; Fight for Sight, New York, New York; and the Ralph and Sophie Heintz Lab and Lecture Fund (T.P.M.). Drs. Kuppermann and Martin have served as consultants to Bausch & Lomb/Chiron Vision.
☆☆ InternetAdvance publication at ajo.com Nov 7, 2002.
ABSTRACT