Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. The Cytomegalovirus Retreatment Trial. The Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group.
OBJECTIVE
To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.


METHODS
Multicenter, randomized, controlled clinical trial.


METHODS
Ophthalmology, and acquired immunodeficiency syndrome (AIDS) services at tertiary care medical centers.


METHODS
Two hundred seventy-nine patients with AIDS and either persistently active or relapsed CMV retinitis.


METHODS
Patients were randomized to one of three therapeutic regimens: induction with foscarnet sodium at 90 mg/kg intravenously every 12 hours for 2 weeks, followed by maintenance at a dosage of 120 mg/kg per day (foscarnet group); induction with ganciclovir sodium at 5 mg/kg intravenously every 12 hours for 2 weeks followed by maintenance at 10 mg/kg per day (ganciclovir group); or continuation of previous 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).


RESULTS
Mortality, retinitis progression, visual acuity, visual fields, and morbidity.


RESULTS
The mortality rate was similar among the three groups. Median survival times were as follows: foscarnet group, 8.4 months; ganciclovir 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), revealed that combination therapy was the most effective regimen for controlling the retinitis. The median times to retinitis progression were as follows: foscarnet group, 1.3 months; ganciclovir group, 2.0 months; and combination therapy group, 4.3 months (P<.001). Although no difference could be detected in visual acuity outcomes, visual field loss and retinal area involvement on fundus photographs both paralleled the progression results, with the most favorable results in the combination therapy group. The rates of visual field loss were as follows: foscarnet 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 effects were similar among the three treatment groups, combination therapy was associated with the greatest negative impact of treatment on quality-of-life measures.


CONCLUSIONS
For patients with AIDS and CMV retinitis whose retinitis has relapsed and who can tolerate both drugs, combination therapy appears to be the most effective therapy for controlling CMV retinitis.
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D017245:Foscarnet / Q000008:administration & dosage / Q000627:therapeutic use*; D005654:Fundus Oculi; D015774:Ganciclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009017:Morbidity; D011788:Quality of Life; D012008:Recurrence; D012173:Retinitis / Q000503:physiopathology; D015996:Survival Rate; D014792:Visual Acuity; D014794:Visual Fields
D000998:Antiviral Agents; D017245:Foscarnet; D015774:Ganciclovir