Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy.
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.
Department of Virology, Royal Free and University College Medical School of University College London, England.
E F
EF
Bowen
J M
JM
Cherrington
P D
PD
Lamy
P D
PD
Griffiths
M A
MA
Johnson
V C
VC
Emery
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000998:Antiviral Agents / Q000627:therapeutic use*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D015774:Ganciclovir / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D009154:Mutation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011446:Prospective Studies; D012173:Retinitis / Q000150:complications / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014764:Viral Proteins
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D003596:Cytosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase; D000077404:Cidofovir; D015774:Ganciclovir