Mutations in the Cytomegalovirus UL97 Gene Associated with Ganciclovir- Resistant Retinitis

Vitreous from patients with cytomegalovirus (CMV) retinitis was studied in order to identify mutations in the CMV UL97 gene associated with clinical resistance to ganciclovir. Point mutations known to confer resistance (V460, I460, V594, and S595) were found in 6 of 11 study eyes. Rapid genetic screening by restriction enzyme analysis of viral DNA amplified directly from the vitreous was as effective as conventional sequencing in detecting these mutations. Repeat biopsy of 3 eyes revealed no change in the UL97 genotype. The UL97 genotype differed between eyes in 2 of 3 patients with bilateral, clinically resistant CMV retinitis. In summary, resistance mutations of the CMV UL97 gene are found in the vitreous of some, but not all, eyes with CMV retinitis that have not responded to ganciclovir therapy. These mutations can differ between eyes in patients with bilateral disease and can be rapidly detected using restriction digest analysis of polymerase chain reaction–amplified viral DNA. Cytomegalovirus (CMV) is the most common intraocular 3 patients whose change in therapy was based on results of in vitro antiviral sensitivity testing. As the number of humaninfection associated with AIDS [1–3]. Progression of CMV retinitis despite antiviral therapy may be due to a number of immunodeficiency virus (HIV)–infected patients continues to rise and the survival time after the development of CMV retini-factors. These include poor patient compliance, progressiv