Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis

Cytomegalovirus (CMV) retinitis is among the most common opportunistic infe ctions in patients with acquired immunodeficiency syndrome. In a prospectiv e study of 210 patients with CMV retinitis, 26 were identified as having ei ther a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC50 >6.0 mum f or ganciclovir, the sensitivity and specificity for detecting a UL97 mutati on were 95% and 98%, respectively, whereas for an IC50 >8.0 muM they were 7 9% and 99%, respectively. Although there were trade- offs between the 2 thr esholds for blood culture isolates, for urine culture isolates an IC50 >8.0 muM appeared to be better at identifying genotypic resistance. UL97 mutati ons identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High- level ganciclovir resistance (IC50, >30 muM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.