Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis

The emergence of mutations conferring ganciclovir resistance was evaluated in an open-label randomized clinical trial that compared oral valganciclovi r with intravenous ganciclovir as induction therapy, followed by maintenanc e with valganciclovir, for newly diagnosed cytomegalovirus (CMV) retinitis in 148 patients with acquired immunodeficiency syndrome. The presence of CM V mutations was directly assessed in patient leukocytes by polymerase chain reaction, followed by restriction fragment-length polymorphism (RFLP) for detection of the most common UL97 mutations associated with ganciclovir res istance and by sequencing of the viral UL97 gene. The cumulative percentage s of patients with UL97-mutant viruses at 3, 6, 12, and 18 months (based on the number of patients on treatment at each time point) was 2.2%, 6.5%, 12 .8%, and 15.3%, respectively. Of the 20 relevant UL97 mutations found by se quencing in 14 patients, 14 (70%) were detected by RFLP analysis. The rate of emergence of ganciclovir-resistant viruses with use of oral valganciclov ir is no greater than that reported with use of intravenous ganciclovir.