Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group.

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 > 0.02), 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 mumol/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.