 |
|
Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance
Irene L. Smith, PhD;
Ibrahim Taskintuna, MD;
Firas M. Rahhal, MD;
Henry C. Powell, MD;
Everett Ai, MD;
Arthur J. Mueller, MD;
Stephen A. Spector, MD;
William R. Freeman, MD
Arch Ophthalmol. 1998;116:178-185.
Objectives To determine the incidence of clinical resistance to intraocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis, and to identify virologic features associated with cidofovir treatment failure.
Patients and Methods Clinical resistance to intravitreal cidofovir was examined in 64 patients with CMV retinitis who received at least 1 injection of 20 µg of cidofovir. Histopathologic examination, culture, and polymerase chain reaction were used to detect CMV in ocular specimens. Antiviral resistance was assessed by plaque reduction assay and DNA sequencing.
Results Clinical resistance to intravitreal cidofovir injections was identified in 3 patients (5%) and was associated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir- and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistance-associated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous. In 1 patient, different resistance mutations were identified in ocular vs extraocular CMV strains.
Conclusions Clinical failure of intravitreal cidofovir occurs infrequently, but may be associated with cidofovir-resistant CMV selected by prior ganciclovir or cidofovir treatment. Ocular CMV disease can result from a localized infection with a resistant CMV strain, and antiviral resistance may develop at a local site of infection independently from resistance that develops systemically.
From the Departments of Pediatrics (Drs Smith and Spector), Ophthalmology (Drs Taskintuna, Rahhal, Mueller, and Freeman), and Pathology (Dr Powell) and the Centers for Molecular Genetics and AIDS Research (Dr Spector), University of California at San Diego, La Jolla; and Pacific Medical Center, San Francisco, Calif (Dr Ai).
RELATED ARTICLE
Immune Recovery Vitritis Associated With Inactive Cytomegalovirus Retinitis: A New Syndrome
Marietta P. Karavellas, Careen Y. Lowder, J. Christopher Macdonald, Cesar P. Avila, Jr, and William R. Freeman
Arch Ophthalmol. 1998;116(2):169-175.
ABSTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Characterization of the Human Cytomegalovirus gH/gL/UL128-131 Complex That Mediates Entry into Epithelial and Endothelial Cells
Ryckman et al.
J. Virol. 2008;82:60-70.
ABSTRACT
| FULL TEXT
Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection.
Maheshwari et al.
J. Leukoc. Biol. 2006;80:1111-1117.
ABSTRACT
| FULL TEXT
Human Cytomegalovirus Entry into Epithelial and Endothelial Cells Depends on Genes UL128 to UL150 and Occurs by Endocytosis and Low-pH Fusion
Ryckman et al.
J. Virol. 2006;80:710-722.
ABSTRACT
| FULL TEXT
New Reporter Cell Line To Evaluate the Sequential Emergence of Multiple Human Cytomegalovirus Mutations during In Vitro Drug Exposure
Gilbert and Boivin
Antimicrob. Agents Chemother. 2005;49:4860-4866.
ABSTRACT
| FULL TEXT
Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism
Wang and Shenk
J. Virol. 2005;79:10330-10338.
ABSTRACT
| FULL TEXT
Human Cytomegalovirus Resistance to Antiviral Drugs
Gilbert and Boivin
Antimicrob. Agents Chemother. 2005;49:873-883.
FULL TEXT
Coding potential of laboratory and clinical strains of human cytomegalovirus
Murphy et al.
Proc. Natl. Acad. Sci. USA 2003;100:14976-14981.
ABSTRACT
| FULL TEXT
Human cytomegalovirus resistance to antiviral drugs: diagnosis, monitoring and clinical impact
Baldanti and Gerna
J Antimicrob Chemother 2003;52:324-330.
ABSTRACT
| FULL TEXT
The Antiviral Resistance and Replication of Cidofovir-Resistant Adenovirus Variants in the New Zealand White Rabbit Ocular Model
Romanowski et al.
IOVS 2001;42:1812-1815.
ABSTRACT
| FULL TEXT
Resistance of Human Cytomegalovirus to Antiviral Drugs
Erice
Clin. Microbiol. Rev. 1999;12:286-297.
ABSTRACT
| FULL TEXT
|
