Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group Report Number 8

PURPOSE: Cytomegalovirus retinitis is the most com, mon intraocular infecti on in patients with acquired immunodeficiency syndrome (AIDS). With prolong ed suppressive anticytomegalovirus maintenance therapy, resistance occurs i n over 25% of patients. We evaluated longitudinal changes in the cytomegalo virus genotype in patients with cytomegalovirus retinitis who developed gan ciclovir resistance that was demonstrated in either the blood or urine. METHODS: Patients with AIDS and previously untreated cytomegalovirus retini tis were followed prospectively for the occurrence of resistance while on t reatment. Blood and urine specimens were obtained periodically for cytomega lovirus culture according to a predetermined schedule. Positive isolates we re tested for phenotypic susceptibility and for mutations in the UL97 and U L54 genes. RESULTS: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a geno typically resistant virus developed increasing phenotypic resistance over t ime. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, th ere was a suggestion that a mixed population of cytomegalovirus might be pr esent. Progression of the retinitis in an involved eye (15 of 18), contrala teral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus. CONCLUSION: Resistance-conferring mutations in the cytomegalovirus genome e merge and may persist when the selective pressure for resistance is maintai ned. Some patients appear to harbor complex subpopulations of virus with di fferent mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytom egalovirus genotype identified. (C) 2001 by Elsevier Science Inc. All right s reserved.