Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome

PURPOSE: In this study we evaluated the safety and efficacy of the nucleoside phosphonate analogue intravitreal cidofovir to treat cytomegalovirus retinitis in humans. METHODS: We conducted a phase I/II unmasked consecutive case series in a single-center institutional referral practice. Eligible patients with the acquired immunodeficiency syndrome had active cytomegalovirus retinitis in at least one eye, despite adequate intravenous therapy with ganciclovir or foscarnet, were intolerant to intravenous therapy, were noncompliant with intravenous therapy, or refused intravenous therapy. In a preliminary safety study (Group 1), ten eyes of nine patients received 14 injections of cidofovir while being treated concurrently with intravenous ganciclovir. In a dose-escalating efficacy study (Group 2), eight eyes of seven patients received 11 injections of cidofovir as sole treatment for cytomegalovirus retinitis. The primary outcome was time to retinitis progression. RESULTS: In the Group 1 eyes receiving 20 μg of cidofovir, the median time to retinitis progression was between 49 and 92 days (mean, 78 days). In Group 2 eyes treated with 20 μg cidofovir, the median time to retinitis progression was 64 days (mean, 63 days). Hypotony occurred in the two eyes treated with a 100-μg dose of cidofovir and in one of three eyes receiving a 40-μg dose. No adverse effects resulted from the remaining 20 cidofovir injections. CONCLUSIONS: Cidofovir (also known as HPMPC) appears to be safe and effective for the local treatment of cytomegalovirus retinitis, providing a long duration of antiviral effect. These preliminary results indicate that additional studies should be performed to investigate more fully this promising medication.