COMBINATION FOSCARNET AND GANCICLOVIR THERAPY VS MONOTHERAPY FOR THE TREATMENT OF RELAPSED CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH AIDS - THE CYTOMEGALOVIRUS RETREATMENT TRIAL

Objective: To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retini tis. Design: Multicenter, randomized, controlled clinical trial. Setti ng: Ophthalmology and acquired immunodeficiency syndrome (AIDS) servic es at tertiary care medical centers. Patients: Two hundred seventy-nin e patients with AIDS and either persistently active or relapsed CMV re tinitis. Intervention: Patients were randomized to one of three therap eutic regimens: induction with foscarnet sodium at 90 mg/kg intravenou sly every 12 hours for 2 weeks, followed by maintenance at a dosage of 120 mg/kg per day (foscar net group); induction with ganciclovir sodi um at 5 mg/kg intravenously every 12 hours for 2 weeks followed by mai ntenance at 10 mg/kg per day (ganciclovir group); or continuation of p revious maintenance therapy plus induction with the other drug (either ganciclovir or foscarnet) for 2 weeks followed by maintenance therapy with both drugs, ganciclovir sodium at 5 mg/kg per day and foscarnet sodium at 90 mg/kg per day (combination therapy group). Outcomes: Mort ality, retinitis progression, visual acuity, visual fields, and morbid ity. Results: The mortality rate was similar among the three groups. M edian survival times were as follows: foscarnet group, 8.4 months; gan ciclovir group, 9.0 months; and combination therapy group, 8.6 months (P=.89). Comparison of retinitis progression, as evaluated in a masked fashion by the centralized Fundus Photograph Reading Center (FPRC), r evealed that combination therapy was the most effective regimen for co ntrolling the retinitis. The median times to retinitis progression wer e as follows: foscarnet group, 1.3 months; ganciclovir group, 2.0 mont hs; and combination therapy group, 4.3 months (P<.001). Although no di fference could be detected in visual acuity outcomes, visual field los s and retinal area involvement on fundus photographs both paralleled t he progression results, with the most favorable results in the combina tion therapy group. The rates of visual field loss were as follows: fo scarnet group, 28 degrees per month; ganciclovir group, 18 degrees per month; combination therapy group, 16 degrees per month (P=.009), and the rates of increase of retinal area involved by CMV were as follows: foscarnet group, 2.47% per month; ganciclovir group, 1.40% per month; and combination therapy group, 1.19% per month (P=.04). While side ef fects were similar among the three treatment groups, combination thera py was associated with the greatest negative impact of treatment on qu ality-of-life measures. Conclusions: For patients with AIDS and CMV re tinitis whose retinitis has relapsed and who can tolerate both drugs, combination therapy appears to be the most effective therapy for contr olling CMV retinitis.