Cytomegalovirus (CMV) resistance in patients with CMV retinitis and AIDS treated with oral or intravenous ganciclovir

Treatment of cytomegalovirus (CMV) retinitis with oral ganciclovir results in relatively low plasma concentrations of drug, which theoretically could cause more frequent viral resistance compared with intravenous (iv) ganciclovir. By use of a plaque-reduction assay to quantify phenotypic sensitivity to ganciclovir, virus isolates were studied from patients with CMV retinitis participating in four clinical trials of oral ganciclovir, Before treatment, 69% of patients were culture-positive but just 1.1% of patients yielded a resistant CMV, defined as a median inhibitory concentration (IC50) >6 mu M. On treatment, the first resistant isolate was recovered at 50 days. Overall, 3.1% of patients receiving iv ganciclovir and 6.5% of those taking oral ganciclovir shed resistant CMV (median ganciclovir exposures of 75 and 165 days, respectively). Since IC(50)s for clinical isolates increased proportionately with treatment duration, it is likely that viral resistance would be more frequent with longer treatment.