Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy

E F Bowen; J M Cherrington; P D Lamy; P D Griffiths; M A Johnson; V C Emery

Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy

J Med Virol. 1999 Aug;58(4):402-7.

Authors

E F Bowen¹, J M Cherrington, P D Lamy, P D Griffiths, M A Johnson, V C Emery

Affiliation

¹ Department of Virology, Royal Free and University College Medical School of University College London, England.

PMID: 10421408

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acquired Immunodeficiency Syndrome / complications
Acquired Immunodeficiency Syndrome / drug therapy*
Antiviral Agents / therapeutic use*
Cidofovir
Cytomegalovirus / genetics*
Cytomegalovirus Infections / complications
Cytomegalovirus Infections / virology
Cytosine / analogs & derivatives
Cytosine / therapeutic use
DNA, Viral / blood*
DNA, Viral / genetics
DNA-Directed DNA Polymerase / genetics*
Ganciclovir / therapeutic use
Genotype
Humans
Mutation
Organophosphonates*
Organophosphorus Compounds / therapeutic use
Phosphotransferases (Alcohol Group Acceptor) / genetics*
Prospective Studies
Retinitis / complications
Retinitis / pathology
Retinitis / virology
Viral Load
Viral Proteins*

Substances

Antiviral Agents
DNA, Viral
Organophosphonates
Organophosphorus Compounds
UL54 protein, Human herpesvirus 5
Viral Proteins
Cytosine
Phosphotransferases (Alcohol Group Acceptor)
ganciclovir kinase
DNA-Directed DNA Polymerase
Cidofovir
Ganciclovir