Phase I/II Study of Intravitreal Cidofovir for the Treatment of Cytomegalovirus Retinitis in Patients With the Acquired Immunodeficiency Syndrome

Kirsch, Leonard S.; Arévalo, J. Fernando; Clercq, Erik De; Paz, Eugenio Chavez de la; Munguia, David; Garcia, Roberto; Freeman, William R.

doi:10.1016/s0002-9394(14)71233-4

Cited by 89 publications

(16 citation statements)

References 39 publications

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“…[22][23][24][25] In these patients, CMV retinitis remained healed or stabilized with consecutive cidofovir injections. However, 3 (5%) of 64 patients demonstrated clinical resistance.…”

Section: Resultsmentioning

confidence: 83%

“…11,12 The longterm use of ganciclovir and foscarnet has been associated with the development of antiviral-resistant strains, [13][14][15][16][17] which harbor viral DNA polymerase gene (UL54) or kinase gene (UL97) mutations. [17][18][19][20][21] Our group initiated the use of intravitreal cidofovir for the treatment of CMV retinitis 22 and has shown that intravitreal injections of 20 µg of cidofovir are effective in the control of newly diagnosed and previously treated CMV retinitis. [23][24][25][26] In this article, we examine the incidence of clinical resistance to intravitreal injections of 20 µg of cidofovir and find antiviral-resistant CMV strains that contain both DNA polymerase and UL97 gene mutations to be associated with the clinical failure of cidofovir.…”

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confidence: 99%

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Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Smith

Taşkintuna²,

Rahhal³

et al. 1998

Arch Ophthalmol

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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 asso-ciated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir-and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistanceassociated 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.

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“…[22][23][24][25] In these patients, CMV retinitis remained healed or stabilized with consecutive cidofovir injections. However, 3 (5%) of 64 patients demonstrated clinical resistance.…”

Section: Resultsmentioning

confidence: 83%

mentioning

confidence: 99%

Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Smith

Taşkintuna²,

Rahhal³

et al. 1998

Arch Ophthalmol

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“…Phase I/II clinical studies showed that a single intravitreal injection of 20 g of cidofovir was safe and efficacious against CMV retinitis in human eyes for a median time of 55 days. At higher doses (40-100 g/eye), however, the drug caused irreversible ocular hypotony in 33% (at 40 g) and 100% (at 100 g) of eyes [51,52] .…”

Section: Antiviral Agentsmentioning

confidence: 96%

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

et al. 2010

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Aims: Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed. Methods: An extensive search of the literature was performed to review various aspects of drug toxicity in retinal pharmacotherapy. The different major classes of drugs, such as corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics, miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity unrelated to the drug were identified and discussed. Results: Corticosteroids like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage to the retina, but at high doses signs of toxicity have been well documented. Complications like cataract and glaucoma are quite common with corticosteroids. Aminoglycosides showed differences in the type and doses associated with toxic reactions, thereby the following order of toxicity can be described (from most toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin = kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while further studies are necessary in order to clarify the safety of new-generation quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were demonstrated to be safe to the retina in cell culture, animals and humans at high doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like diclofenac needs further evaluation. Preservatives like benzyl alcohol and changes in pH or osmolarity exert an influence on the toxic effects of intravitreally applied drugs. Conclusions: A great number of drugs are now used mainly intravitreally without relevant retinal toxicity.

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“…Cidofovir has also proved efficacious, on intravitreal injection, against CMV retinitis (in patients with AIDS) (112,113), although intravitreal injection of HPMPC should be used with caution because of the risk of anterior uveitis and decrease of intraocular pressure (15).…”

Section: Clinical Usefulness Cidofovirmentioning

confidence: 99%

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

2003

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The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily)

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Phase I/II Study of Intravitreal Cidofovir for the Treatment of Cytomegalovirus Retinitis in Patients With the Acquired Immunodeficiency Syndrome

Cited by 89 publications

References 39 publications

Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

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