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 ga nciclovir (GCV) therapy were followed with serial blood sampling to detectc hanges both in CMV load and in the genetic composition of genes UL97 and UL 54 whilst receiving cidofovir (CDV) therapy. CDV neither reduced CMV load i n blood nor prevented its quantitative resurgence during therapy. These eff ects were not explained by the initial presence or development of CDV-assoc iated drug resistance mutations in UL54. In two patients, UL97 genotypic re sistance to GCV involving either a L595S mutation or a deletion of amino ac ids 590-603 were present at the initiation of CDV and, in both patients, re population of CMV strains with wild-type UL97 sequences occurred during CDV therapy. These data are consistent with GCV-resistant strains containing U L97 mutations being less fit than their wild-type counterparts and so being able to persist only with the selective pressure of GCV. J. Med. Virol. 58 :402-407, 1999. (C) 1999 Wiley-Liss, Inc.