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ARTICLE

Parenteral Cidofovir for Cytomegalovirus Retinitis in Patients with AIDS: The HPMPC Peripheral Cytomegalovirus Retinitis Trial: A Randomized, Controlled Trial

15 February 1997 | Volume 126 Issue 4 | Pages 264-274

Background: Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodeficiency syndrome (AIDS).

Objective: To evaluate intravenous cidofovir as a treatment for CMV retinitis.

Design: Two-stage, multicenter, phase II/III, randomized, controlled clinical trial.

Setting: Ophthalmology and AIDS services at tertiary care medical centers.

Patients: 64 patients with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity).

Intervention: Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3 mg/kg once every 2 weeks; or the high-dose cidofovir group, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was administered with hydration and probenecid.

Measurements: Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal area involved by CMV; the loss of visual acuity; and morbidity.

Results: Median time to progression was 64 days in the low-dose cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The median time to progression was not reached in the high-dose cidofovir group but was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the rates of increase in the retinal area affected by CMV confirmed the data on time to progression. The three groups had similar rates of visual loss. Proteinuria of 2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8 per person-year in the low-dose cidofovir group (P > 0.2), and 6.8 per person-year in the high-dose cidofovir group (P = 0.135). No patient developed 4+ proteinuria, but two cidofovir recipients developed persistent elevations of serum creatinine levels at more than 177 µmol/L (2.0 mg/dL). Reactions to probenecid occurred at a rate of 0.70 per person-year.

Conclusions: Intravenous cidofovir, high- or low-dose, effectively slowed the progression of CMV retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and monitoring for proteinuria seemed to minimize but not eliminate the risk for nephrotoxicity.

Author and Article Information
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Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group*.

*For a list of participating persons and centers, see the Appendix.

Note: This trial is registered as #281 in the AIDS Clinical Trials Group registry. The registry is located at 6101 Executive Boulevard, Suite 200, Rockville, MD 20852; telephone 301-230-3150.

Grant Support: In part by cooperative agreements from the National Eye Institute to the Johns Hopkins University School of Medicine (U10 EY 08052), the Johns Hopkins University School of Hygiene and Public Health (U10 EY 08057), and the University of Wisconsin School of Medicine (U10 EY 08067). Additional support was provided by the National Center for Research Resources through General Clinical Research Center grants 5M01 RR 00350 (Baylor College of Medicine), 5M01 RR 00035 and 5M01 RR 00722 (Johns Hopkins University), 5M01 RR 05096 (Louisiana State University at Tulane), 5M01 RR 00071 (Mount Sinai Medical Center), 5M01 RR 00048 (Northwestern University), 5M01 RR 000865 (University of California, Los Angeles), 5M01 RR 00083 (University of California, San Francisco), 5M01 RR 05280 (University of Miami), and 5M01 RR 00046 (University of North Carolina). Support was also provided by the National Institute of Allergy and Infectious Diseases through cooperative agreements U01 AI 27668 (Johns Hopkins University), U01 AI 27674 (Louisiana State University at Tulane), U01 AI 27667 (Mount Sinai Medical Center), U01 AI 27665 (New York University), U01 AI 25915 (Northwestern University), U01 AI 27660 (University of California, Los Angeles), U01 AI 27670 (University of California, San Diego), U01 AI 27663 (University of California, San Francisco), and U01 AI25868 (University of North Carolina). Drugs and additional support were provided by Gilead Sciences, Inc. (Foster City, California). Financial disclosure statements are on file at the Studies of Ocular Complications of AIDS Coordinating Center, Johns Hopkins University School of Hygiene and Public Health, 601 North Wolfe Street, Room 5010, Baltimore, MD 21287.

Requests for Reprints: Douglas A. Jabs, MD, Studies of Ocular Complications of AIDS Chairman's Office, the Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, 550 North Broadway, Suite 700, Baltimore, MD 21205.




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