To assess the efficacy of intravitreous fomivirsen sodium, an antisense oligonucleotide, for newly diagnosed peripheral cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS).

Randomized treatment intervention clinical trial.

A multicenter, prospective, and randomized clinical trial compared immediate treatment of CMV retinitis with fomivirsen (165 μg administered intravitreously) to deferral of treatment until CMV retinitis lesions progressed by standard definitions. Included were patients with CMV retinitis lesions at least 750 μm outside of zone 1. Fomivirsen was injected weekly for three doses as induction therapy, followed by injection every other week as maintenance therapy. All patients were examined regularly until evidence of retinitis progression. Time to first progression was determined by two independent masked fundus photography reading centers (principal outcome) and by clinician investigators based on indirect ophthalmoscopy. Patients in the deferral of treatment group were offered fomivirsen therapy at the time of clinically determined retinitis progression.

Patients in the immediate treatment group (n = 18) and the deferral of treatment group (n = 10) were comparable at baseline. Median time to first progression of disease for the immediate treatment group was 71 days (95% confidence interval [CI] 28 days—not determinable) and for the deferral of treatment group was 13 days (95% CI 9–15 days; P = .0001, Wilcoxon rank sum test). Progression occurred in 44% of patients in the immediate treatment group during the study compared with 70% of patients in the deferral of treatment group during the study. There were no retinal detachments among eyes treated with fomivirsen.

Fomivirsen is an effective treatment for CMV retinitis in patients with AIDS that utilizes a mechanism of action different than that of ganciclovir, foscarnet, and cidofovir.