Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis.
The emergence of mutations conferring ganciclovir resistance was evaluated in an open-label randomized clinical trial that compared oral valganciclovir with intravenous ganciclovir as induction therapy, followed by maintenance with valganciclovir, for newly diagnosed cytomegalovirus (CMV) retinitis in 148 patients with acquired immunodeficiency syndrome. The presence of CMV mutations was directly assessed in patient leukocytes by polymerase chain reaction, followed by restriction fragment-length polymorphism (RFLP) for detection of the most common UL97 mutations associated with ganciclovir resistance and by sequencing of the viral UL97 gene. The cumulative percentages of patients with UL97-mutant viruses at 3, 6, 12, and 18 months (based on the number of patients on treatment at each time point) was 2.2%, 6.5%, 12.8%, and 15.3%, respectively. Of the 20 relevant UL97 mutations found by sequencing in 14 patients, 14 (70%) were detected by RFLP analysis. The rate of emergence of ganciclovir-resistant viruses with use of oral valganciclovir is no greater than that reported with use of intravenous ganciclovir.
Boivin
G
G
Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec, Sainte-Foy, Quebec, Canada G1V 4G2. Guy.Boivin@crchul.ulaval.ca
Gilbert
C
C
Gaudreau
A
A
Greenfield
I
I
Sudlow
R
R
Roberts
N A
NA
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000821:virology; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000821:virology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007962:Leukocytes / Q000821:virology; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D000077562:Valganciclovir; D014764:Viral Proteins
D000998:Antiviral Agents; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase; D000077562:Valganciclovir; D015774:Ganciclovir