Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance
- PMID: 9488269
- DOI: 10.1001/archopht.116.2.178
Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance
Abstract
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 pg 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.
Similar articles
-
Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.Ophthalmology. 1995 Apr;102(4):533-42; discussion 542-3. doi: 10.1016/s0161-6420(95)30985-2. Ophthalmology. 1995. PMID: 7724170 Clinical Trial.
-
Low-dose intravitreal cidofovir (HPMPC) therapy of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.Ophthalmology. 1997 Jun;104(6):1049-57. doi: 10.1016/s0161-6420(97)30188-2. Ophthalmology. 1997. PMID: 9186448
-
Therapeutic options for resistant cytomegalovirus retinitis.J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14 Suppl 1:S13-21. doi: 10.1097/00042560-199700001-00004. J Acquir Immune Defic Syndr Hum Retrovirol. 1997. PMID: 9058613 Review.
-
New developments in the treatment of CMV retinitis.Ophthalmology. 1996 Jul;103(7):999-1000. doi: 10.1016/s0161-6420(96)30548-4. Ophthalmology. 1996. PMID: 8684813 No abstract available.
-
Cidofovir: a review of its use in cytomegalovirus retinitis in patients with AIDS.Drugs. 1999 Aug;58(2):325-45. doi: 10.2165/00003495-199958020-00015. Drugs. 1999. PMID: 10473024 Review.
Cited by
-
Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture In Vitro.J Virol. 2016 Mar 28;90(8):3929-43. doi: 10.1128/JVI.02858-15. Print 2016 Apr. J Virol. 2016. PMID: 26842472 Free PMC article.
-
Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China.Infect Dis Ther. 2021 Sep;10(3):1309-1322. doi: 10.1007/s40121-021-00452-4. Epub 2021 May 8. Infect Dis Ther. 2021. PMID: 33966176 Free PMC article.
-
Human cytomegalovirus early protein pUL21a promotes efficient viral DNA synthesis and the late accumulation of immediate-early transcripts.J Virol. 2011 Jan;85(2):663-74. doi: 10.1128/JVI.01599-10. Epub 2010 Nov 3. J Virol. 2011. PMID: 21047969 Free PMC article.
-
Distinct Properties of Human Cytomegalovirus Strains and the Appropriate Choice of Strains for Particular Studies.Methods Mol Biol. 2021;2244:19-38. doi: 10.1007/978-1-0716-1111-1_2. Methods Mol Biol. 2021. PMID: 33555580
-
The ULb' region of the human cytomegalovirus genome confers an increased requirement for the viral protein kinase UL97.J Virol. 2013 Jun;87(11):6359-76. doi: 10.1128/JVI.03477-12. Epub 2013 Mar 27. J Virol. 2013. PMID: 23536674 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical