Discordant phenotypes and genotypes of cytomegalovirus (CMV) in patients with AIDS and relapsing CMV retinitis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The presence of mixed viral populations in blood samples of AIDS patients and the potential selection bias introduced by susceptibility testing may underestimate the real impact of CMV resistance in patients failing antiviral therapy.
Gilbert
Christian
C
Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Laval, Laval University, 2705 boulevard Laurier Sainte-Foy, Québec City, Canada G1V 4G2.
Boivin
Guy
G
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics*; D017726:Cytomegalovirus Retinitis / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics*; D015774:Ganciclovir / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012008:Recurrence; D017211:Treatment Failure
D000998:Antiviral Agents; D004279:DNA, Viral; D015774:Ganciclovir