 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
15 February 1997 | Volume 126 Issue 4 | Pages 257-263
Background: Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with the acquired immunodeficiency syndrome (AIDS). If left untreated, it may lead to progressive destruction of retinal tissue and blindness. Cidofovir is a nucleotide analogue of cytosine that has potent, prolonged in vitro and in vivo activity against herpesviruses, including many CMV isolates that are resistant to ganciclovir and foscarnet.
Objective: To determine whether intravenous cidofovir delays progression of previously untreated CMV retinitis.
Design: Randomized, controlled trial comparing immediate with deferred cidofovir treatment. Patients in the deferred treatment group were eligible to receive cidofovir after progression of CMV retinitis was documented by retinal photography.
Setting: Eight academic medical centers and an independent center that read retinal photographs.
Patients: 48 patients with AIDS and previously untreated peripheral CMV retinitis who were randomly assigned to immediate (n = 25) or deferred treatment (n = 23).
Intervention: Intravenous cidofovir, 5 mg/kg of body weight, once weekly for 2 weeks and then once every other week. To minimize nephrotoxicity, oral probenecid and intravenous hydration with normal saline were administered with each cidofovir infusion.
Measurements: Progression of CMV retinitis was assessed by bilateral, full-field retinal photographs that were read by an ophthalmologist who was masked to treatment assignment. Incidence of side effects, changes in visual acuity, effect on CMV shedding in urine and blood, and mortality were also assessed.
Results: The median time to progression of CMV retinitis was 22 days (95% CI, 10 to 27 days) in the deferred treatment group and 120 days (CI, 40 to 134 days) in the immediate treatment group (P < 0.001). Neutropenia (15%) and proteinuria (12%), both asymptomatic, were the most common serious adverse events considered to be possibly related to cidofovir. Cidofovir treatment was discontinued in 10 of 41 patients (24%) because of protocol-defined treatment-limiting nephrotoxicity. Transient reactions to probenecid, including mild to moderate constitutional symptoms or nausea, occurred in 23 of 41 patients (56%) and were dose limiting in 3 (7%).
Conclusions: Cidofovir was efficacious in delaying progression of previously untreated CMV retinitis. Treatment was associated with manageable side effects; strict adherence to monitoring of renal function before cidofovir was administered and concomitant administration of probenecid and saline hydration appeared to minimize drug-related nephrotoxicity.
Author and Article Information
For author affiliations and current author addresses, see end of text.
ARTICLE
Intravenous Cidofovir for Peripheral Cytomegalovirus Retinitis in Patients with AIDS
A Randomized, Controlled Trial
Grant Support: By Gilead Sciences, Inc.
Requests for Reprints: Jacob P. Lalezari, MD, Quest Clinical Research, 2300 Sutter Street, Suite 202, San Francisco, CA 94115.
Current Author Addresses: Dr. Lalezari: Quest Clinical Research, 2300 Sutter Street, Suite 202, San Francisco, CA 94115.
This article has been cited by other articles:
|
|
 |
|
  C. R. Rayner, P. Chanu, R. Gieschke, L. M. Boak, and E. N. Jonsson Population Pharmacokinetics of Oseltamivir When Coadministered With Probenecid J. Clin. Pharmacol., August 1, 2008; 48(8): 935 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cihlar, A. S. Ray, C. G. Boojamra, L. Zhang, H. Hui, G. Laflamme, J. E. Vela, D. Grant, J. Chen, F. Myrick, et al. Design and Profiling of GS-9148, a Novel Nucleotide Analog Active against Nucleoside-Resistant Variants of Human Immunodeficiency Virus Type 1, and Its Orally Bioavailable Phosphonoamidate Prodrug, GS-9131 Antimicrob. Agents Chemother., February 1, 2008; 52(2): 655 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Bohl and D. C. Brennan BK Virus Nephropathy and Kidney Transplantation Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(Supplement_1): S36 - S46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Imaoka, H. Kusuhara, M. Adachi, J. D. Schuetz, K. Takeuchi, and Y. Sugiyama Functional Involvement of Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) in the Renal Elimination of the Antiviral Drugs Adefovir and Tenofovir Mol. Pharmacol., February 1, 2007; 71(2): 619 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. White, D. I. Choo, G. Stroup, and M. R. Schleiss The effect of cidofovir on cytomegalovirus-induced hearing loss in a Guinea pig model. Arch Otolaryngol Head Neck Surg, June 1, 2006; 132(6): 608 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T D Sudarsanam, R D Sahni, and G T John Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections. Postgrad. Med. J., May 1, 2006; 82(967): 313 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, S. Rippen, L. Barone, C. Burns, G. Rhodes, S. Tohan, et al. An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice from Lethal Orthopoxvirus Challenge J. Virol., October 15, 2005; 79(20): 13139 - 13149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Mandell, E. M. Arjmand, D. J. Kay, M. L. Casselbrant, and C. A. Rosen Intralesional Cidofovir for Pediatric Recurrent Respiratory Papillomatosis Arch Otolaryngol Head Neck Surg, November 1, 2004; 130(11): 1319 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Jabs AIDS and Ophthalmology in 2004 Arch Ophthalmol, July 1, 2004; 122(7): 1040 - 1042. [Full Text] [PDF]
|
|
|
|
 |
|
 E. De Clercq Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections Clin. Microbiol. Rev., October 1, 2003; 16(4): 569 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Keith, M. J. M. Hitchcock, W. A. Lee, A. Holy, and E. R. Kern Evaluation of Nucleoside Phosphonates and Their Analogs and Prodrugs for Inhibition of Orthopoxvirus Replication Antimicrob. Agents Chemother., July 1, 2003; 47(7): 2193 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Wolf, C. A. Rodriguez, M. Mucci, A. Ingrosso, B. A. Duncan, and D. J. Nickens Pharmacokinetics and Renal Effects of Cidofovir with a Reduced Dose of Probenecid in HIV-Infected Patients with Cytomegalovirus Retinitis J. Clin. Pharmacol., January 1, 2003; 43(1): 43 - 51. [Abstract] [Full Text]
|
|
|
|
|
|
J. P. Lalezari, J. A. Aberg, L. H. Wang, M. B. Wire, R. Miner, W. Snowden, C. L. Talarico, S. Shaw, M. A. Jacobson, and W. L. Drew Phase I Dose Escalation Trial Evaluating the Pharmacokinetics, Anti-Human Cytomegalovirus (HCMV) Activity, and Safety of 1263W94 in Human Immunodeficiency Virus-Infected Men with Asymptomatic HCMV Shedding Antimicrob. Agents Chemother., September 1, 2002; 46(9): 2969 - 2976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Breman and D.A. Henderson Diagnosis and Management of Smallpox N. Engl. J. Med., April 25, 2002; 346(17): 1300 - 1308. [Full Text] [PDF]
|
|
|
|
|
|
D. F. Martin, J. Sierra-Madero, S. Walmsley, R. A. Wolitz, K. Macey, P. Georgiou, C. A. Robinson, M. J. Stempien, and the Valganciclovir Study Group A Controlled Trial of Valganciclovir as Induction Therapy for Cytomegalovirus Retinitis N. Engl. J. Med., April 11, 2002; 346(15): 1119 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meier, S. Dautheville-Guibal, P. M. Ronco, and J. Rossert Cidofovir-induced end-stage renal failure Nephrol. Dial. Transplant., January 1, 2002; 17(1): 148 - 149. [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Miller Nucleoside Phosphonate Interactions with Multiple Organic Anion Transporters in Renal Proximal Tubule J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 567 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Holbrook, C. L. Meinert, M. L. Van Natta, M. Davis, L. Hubbard, D. A. Jabs, and for the Studies of Ocular Complications of AIDS Re Photographic Measures of Cytomegalovirus Retinitis as Surrogates for Visual Outcomes in Treated Patients Arch Ophthalmol, April 1, 2001; 119(4): 554 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ljungman, G. L. Deliliers, U. Platzbecker, S. Matthes-Martin, A. Bacigalupo, H. Einsele, J. Ullmann, M. Musso, R. Trenschel, P. Ribaud, et al. Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients Blood, January 15, 2001; 97(2): 388 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Kempen, D. A. Jabs, J. P. Dunn, S. K. West, and J. Tonascia Retinal Detachment Risk in Cytomegalovirus Retinitis Related to the Acquired Immunodeficiency Syndrome Arch Ophthalmol, January 1, 2001; 119(1): 33 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Torgovnick, E. L Arsura, and D. Lala Cytomegalovirus ventriculoencephalitis presenting as a Wernicke's encephalopathy-like syndrome Neurology, December 26, 2000; 55(12): 1910 - 1913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Purdy Management and Prevention of Opportunistic Infections in the HIV-Infected Patient Journal of Pharmacy Practice, December 1, 2000; 13(6): 475 - 498. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M. Whitcup The Double-Edged Ocular Immune Response: The Cogan Lecture Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3243 - 3248. [Full Text]
|
|
|
|
|
|
S. M. Pransky, D. F. Brewster, A. E. Magit, and D. B. Kearns Clinical Update on 10 Children Treated With Intralesional Cidofovir Injections for Severe Recurrent Respiratory Papillomatosis Arch Otolaryngol Head Neck Surg, October 1, 2000; 126(10): 1239 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wada, M. Tsuda, T. Sekine, S. H. Cha, M. Kimura, Y. Kanai, and H. Endou Rat Multispecific Organic Anion Transporter 1 (rOAT1) Transports Zidovudine, Acyclovir, and Other Antiviral Nucleoside Analogs J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 844 - 849. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. R. Toro, L. V. Wood, N. K. Patel, and M. L. Turner Topical Cidofovir: A Novel Treatment for Recalcitrant Molluscum Contagiosum in Children Infected With Human Immunodeficiency Virus 1 Arch Dermatol, August 1, 2000; 136(8): 983 - 985. [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. HO, D. C. LIN, D. B. MENDEL, and T. CIHLAR Cytotoxicity of Antiviral Nucleotides Adefovir and Cidofovir Is Induced by the Expression of Human Renal Organic Anion Transporter 1 J. Am. Soc. Nephrol., March 1, 2000; 11(3): 383 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Whitcup Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy JAMA, February 2, 2000; 283(5): 653 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Whitcup, E. Fortin, A. S. Lindblad, P. Griffiths, J. A. Metcalf, M. R. Robinson, J. Manischewitz, B. Baird, C. Perry, I. M. Kidd, et al. Discontinuation of Anticytomegalovirus Therapy in Patients With HIV Infection and Cytomegalovirus Retinitis JAMA, November 3, 1999; 282(17): 1633 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pransky, A. E. Magit, D. B. Kearns, D. R. Kang, and N. O. Duncan Intralesional Cidofovir for Recurrent Respiratory Papillomatosis in Children Arch Otolaryngol Head Neck Surg, October 1, 1999; 125(10): 1143 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ambati, K. B Wynne, M. C Angerame, and M. R Robinson Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis Br. J. Ophthalmol., October 1, 1999; 83(10): 1153 - 1158. [Abstract] [Full Text]
|
|
|
|
|
|
T. Cihlar, D. C. Lin, J. B. Pritchard, M. D. Fuller, D. B. Mendel, and D. H. Sweet The Antiviral Nucleotide Analogs Cidofovir and Adefovir Are Novel Substrates for Human and Rat Renal Organic Anion Transporter 1 Mol. Pharmacol., September 1, 1999; 56(3): 570 - 580. [Abstract] [Full Text]
|
|
|
|
|
|
D. A. Henderson, T. V. Inglesby, J. G. Bartlett, M. S. Ascher, E. Eitzen, P. B. Jahrling, J. Hauer, M. Layton, J. McDade, M. T. Osterholm, et al. Smallpox as a Biological Weapon: Medical and Public Health Management JAMA, June 9, 1999; 281(22): 2127 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Martin, B. D. Kuppermann, R. A. Wolitz, A. G. Palestine, H. Li, C. A. Robinson, and The Roche Ganciclovir Study Group Oral Ganciclovir for Patients with Cytomegalovirus Retinitis Treated with a Ganciclovir Implant N. Engl. J. Med., April 8, 1999; 340(14): 1063 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Erice Resistance of Human Cytomegalovirus to Antiviral Drugs Clin. Microbiol. Rev., April 1, 1999; 12(2): 286 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Cundy, P. Barditch-Crovo, B. G. Petty, A. Ruby, M. Redpath, H. S. Jaffe, and P. S. Lietman Clinical Pharmacokinetics of 1-[((S)-2-Hydroxy-2-Oxo-1,4,2-Dioxaphosphorinan-5-yl)methyl]cytosine in Human Immunodeficiency Virus-Infected Patients Antimicrob. Agents Chemother., February 1, 1999; 43(2): 271 - 277. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. J. Whitley, M. A. Jacobson, D. N. Friedberg, G. N. Holland, D. A. Jabs, D. T. Dieterich, W. D. Hardy, M. A. Polis, T. A. Deutsch, J. Feinberg, et al. Guidelines for the Treatment of Cytomegalovirus Diseases in Patients With AIDS in the Era of Potent Antiretroviral Therapy: Recommendations of an International Panel Arch Intern Med, May 11, 1998; 158(9): 957 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. Smith, I. Taskintuna, F. M. Rahhal, H. C. Powell, E. Ai, A. J. Mueller, S. A. Spector, and W. R. Freeman Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance Arch Ophthalmol, February 1, 1998; 116(2): 178 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Musch, D. F. Martin, J. F. Gordon, M. D. Davis, B. D. Kuppermann, and The Ganciclovir Implant Study Group Treatment of Cytomegalovirus Retinitis with a Sustained-Release Ganciclovir Implant N. Engl. J. Med., July 10, 1997; 337(2): 83 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Jacobson Treatment of Cytomegalovirus Retinitis in Patients with the Acquired Immunodeficiency Syndrome N. Engl. J. Med., July 10, 1997; 337(2): 105 - 114. [Full Text] [PDF]
|
|
|
|
 |
|
 Cidofovir Effectively Delays CMV Retinitis AIDS Clinical Care, April 1, 1997; 1997(401): 3 - 3. [Full Text]
|
|
|
|
 |
|
 CIDOFOVIR FOR CYTOMEGALOVIRUS RETINITIS Journal Watch (General), March 4, 1997; 1997(304): 1 - 1. [Full Text]
|
|
|
|
|
|
J. G. Breman and D.A. Henderson Diagnosis and Management of Smallpox N. Engl. J. Med., April 25, 2002; 346(17): 1300 - 1308. [Full Text] [PDF]
|
|
Article
