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1996-03-30
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Document 1054
DOCN M9651054
TI Detection of human cytomegalovirus mutations associated with ganciclovir
resistance in cerebrospinal fluid of AIDS patients with central nervous
system disease.
DT 9505
AU Wolf DG; Lee DJ; Spector SA; Department of Pediatrics, University of
California, San Diego, La; Jolla 92093-0672, USA.
SO Antimicrob Agents Chemother. 1995 Nov;39(11):2552-4. Unique Identifier :
AIDSLINE MED/96139556
AB To examine the involvement of ganciclovir-resistant strains in the
development of central nervous system (CNS) disease caused by human
cytomegalovirus (HCMV), 14 AIDS patients with CNS disease caused by HCMV
were studied for the presence of HCMV strains with UL97 gene mutations
associated with ganciclovir resistance by using amplification and direct
sequencing of HCMV DNA in cerebrospinal fluid (CSF). The CSF of all
seven patients who had not received ganciclovir prior to the development
of CNS disease and four patients who had been receiving the drug for 3
to 8 months contained wild-type UL97 sequences. The CSF of three
patients who had received ganciclovir for 12 to 30 months contained HCMV
strains with nucleotide changes leading to single-amino-acid
substitutions within conserved UL97 sites implicated in nucleotide
binding (position 460) and substrate recognition (position 591).
Patients containing mutant and wild-type strains revealed a similar
spectrum of clinical and histopathologic manifestations. These findings
indicate that CNS disease in AIDS patients receiving prolonged
ganciclovir therapy can be caused by ganciclovir-resistant HCMV strains.
Direct genotypic analysis of HCMV DNA within CSF should help to identify
ganciclovir-resistant virus and to guide anti-HCMV therapy.
DE Antiviral Agents/*PHARMACOLOGY/THERAPEUTIC USE AIDS-Related
Opportunistic Infections/DRUG THERAPY/*VIROLOGY Base Sequence Central
Nervous System Diseases/DRUG THERAPY/*VIROLOGY Cytomegalovirus/DRUG
EFFECTS/*GENETICS Cytomegalovirus Infections/DRUG THERAPY/*VIROLOGY
Drug Resistance, Microbial Ganciclovir/*PHARMACOLOGY/THERAPEUTIC USE
Genotype Human Molecular Sequence Data Mutation Polymerase Chain
Reaction Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).