Change over Time in Incidence of Ganciclovir Resistance in Patients with Cytomegalovirus Retinitis

Abstract

In the mid-1990s, the incidence of cytomegalovirus (CMV) resistance to ganciclovir was estimated to be approximately 25% by 1 year after diagnosis of retinitis in patients with acquired immunodeficiency syndrome. Two hundred fifty-seven patients with CMV retinitis were enrolled in a prospective observational study during 1993-2003 and were treated with ganciclovir. Demographic characteristics and data on CMV disease, antiretroviral therapy, and ganciclovir resistance were recorded for all patients. Human immunodeficiency virus (HIV) load and CMV load were measured for patients enrolled in 1996 or later. Kaplan-Meier and Cox proportional hazards regression methods were used to examine incidence of resistance. The 2-year incidence of resistance was 28% among patients enrolled before 1996 and 9% among those enrolled in or after 1996 (P=.001). All cases of resistance occurred among patients with CD4+ T cell counts <50 cells/microL, and positive CMV culture results at baseline were associated with a approximately 4-fold increase in resistance. Among patients whose CMV and HIV loads were measured, a detectable CMV load at baseline and during follow-up was associated with increased risk of resistance, but a detectable HIV load was not. Rates of resistance have decreased from the high levels seen in the pre-HAART era. Better control of CMV replication may have contributed to this decrease.