Discordant phenotypes and genotypes of Cytomegalovirus (CMV) in patients with AIDS and relapsing CMV retinitis

Publisher Website
Google Scholar
Abstract
To investigate the correlation between genotypic studies performed on blood leukocytes and phenotypic results obtained from the corresponding blood viral isolates in AIDS patients with relapsing cytomegalovirus (CMV) retinitis. Sequential blood samples were collected from patients failing intravenous or oral ganciclovir therapy. The CMV UL97 gene was amplified directly from leukocyte DNA extracts for assessing the presence of viral mutations using restriction fragment length polymorphism analysis and direct sequencing. Positive viral cultures from the same blood samples were also analyzed for their susceptibility to ganciclovir and their UL97 genotype was determined. Discordant CMV genotypes between the clinical specimen and the viral culture were found in at least one blood sample from three of the four patients with relapsing CMV retinitis. Furthermore, some UL97 mutations at known resistance codons (592, 594) were associated with a drug-susceptible phenotype. In all four cases, genotypic analyses of blood samples better correlated with clinical progression than phenotypic analyses of viral cultures. The presence of mixed viral populations in blood samples of AIDS patients and the potential selection bias introduced by in vitro susceptibility testing may underestimate the real impact of CMV resistance in patients failing antiviral therapy.

This publication has 12 references indexed in Scilit: