Longitudinal obervation on mutation conferring ganciclovir reitance in patient with acquired immunodeficiency yndrome and cytomegaloviru retiniti: the cytomegaloviru and viral reitance tudy group report number 8

PURPOE: Cytomegaloviru retiniti i the mot common intraocular infection in patient with acquired immunodeficiency yndrome (AID). With prolonged uppreive anticytomegaloviru maintenance therapy, reitance occur in over 25% of patient. We evaluated longitudinal change in the cytomegaloviru genotype in patient with cytomegaloviru retiniti who developed ganciclovir reitance that wa demontrated in either the blood or urine. METHOD: Patient with AID and previouly untreated cytomegaloviru retiniti were followed propectively for the occurrence of reitance while on treatment. Blood and urine pecimen were obtained periodically for cytomegaloviru culture according to a predetermined chedule. Poitive iolate were teted for phenotypic uceptibility and for mutation in the UL97 and UL54 gene. REULT: A mutation conferring reitance to ganciclovir in either the UL97 or UL54 gene wa detected in 18 patient. In general, patient with a genotypically reitant viru developed increaing phenotypic reitance over time. There wa a uggetion that unle therapy wa changed, UL97 mutation tended to perit. In even of eight patient, the mutation identified in iolate from the blood and urine were identical. In elected patient, there wa a uggetion that a mixed population of cytomegaloviru might be preent. Progreion of the retiniti in an involved eye (15 of 18), contralateral eye retiniti (10 of 11), and extraocular cytomegaloviru dieae (5 of 18) occurred commonly among patient with reitant viru. CONCLUION: Reitance-conferring mutation in the cytomegaloviru genome emerge and may perit when the elective preure for reitance i maintained. ome patient appear to harbor complex ubpopulation of viru with different mutation and different level of phenotypic reitance. Change in therapy may reult in a hift in viru population and change in the cytomegaloviru genotype identified.