PARENTERAL CIDOFOVIR FOR CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH AIDS - THE HPMPC PERIPHERAL CYTOMEGALOVIRUS RETINITIS TRIAL - A RANDOMIZED, CONTROLLED TRIAL

Background: Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodefic iency syndrome (AIDS). Objective: To evaluate intravenous cidofovir as a treatment for CMV retinitis.Design: Two-stage, multicenter, phase I I/III, randomized, controlled clinical trial. Setting: Ophthalmology a nd AIDS services at tertiary care medical centers. Patients: 64 patien ts with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity).Int ervention: Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progr essed; 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 gro up, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then ma intenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minim ize nephrotoxicity, cidofovir was administered with hydration and prob enecid. Measurements: Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal ar ea involved by CMV; the loss of visual acuity; and morbidity. Results: Median time to progression was 64 days in the low-dose cidofovir grou p and 21 days in the deferral group (P = 0.052, log-rank test). The me dian time to progression was not reached in the high-dose cidofovir gr oup 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 simila r 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 hi gh-dose cidofovir group (P = 0.135). No patient developed 4+ proteinur ia, but two cidofovir recipients developed persistent elevations of se rum creatinine levels at more than 177 mu mol/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 pro gression of CMV retinitis. Concomitant probenecid and hydration therap y, intermittent dosing, and monitoring for proteinuria seemed to minim ize but not eliminate the risk for nephrotoxicity.