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Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy.
Bowen EF; Cherrington JM; Lamy PD; Griffiths PD; Johnson MA; Emery VC;
November 30, 1999
J Med Virol. 1999 Aug;58(4):402-7. Unique Identifier : AIDSLINE

Five AIDS patients with cytomegalovirus (CMV) retinitis who had received ganciclovir (GCV) therapy were followed with serial blood sampling to detectchanges both in CMV load and in the genetic composition of genes UL97 and UL54 whilst receiving cidofovir (CDV) therapy. CDV neither reduced CMV load in blood nor prevented its quantitative resurgence during therapy. These effects were not explained by the initial presence or development of CDV-associated drug resistance mutations in UL54. In two patients, UL97 genotypic resistance to GCV involving either a L595S mutation or a deletion of amino acids 590-603 were present at the initiation of CDV and, in both patients, repopulation of CMV strains with wild-type UL97 sequences occurred during CDV therapy. These data are consistent with GCV-resistant strains containing UL97 mutations being less fit than their wild-type counterparts and so being able to persist only with the selective pressure of GCV.

JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/COMPLICATIONS/*DRUG THERAPY Antiviral Agents/*THERAPEUTIC USE Cytomegalovirus/*GENETICS Cytomegalovirus Infections/COMPLICATIONS/VIROLOGY Cytosine/ANALOGS & DERIVATIVES/THERAPEUTIC USE DNA-Directed DNA Polymerase/*GENETICS DNA, Viral/*BLOOD/GENETICS Ganciclovir/THERAPEUTIC USE Genotype Human Mutation Organophosphorus Compounds/THERAPEUTIC USE Phosphotransferases (Alcohol Group Acceptor)/*GENETICS Prospective Studies Retinitis/COMPLICATIONS/PATHOLOGY/VIROLOGY Support, Non-U.S. Gov't Viral Load