CLINICAL FAILURE OF CMV RETINITIS WITH INTRAVITREAL CIDOFOVIR IS ASSOCIATED WITH ANTIVIRAL RESISTANCE

Objectives: To determine the incidence of clinical resistance to intra ocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis, and to identi fy virologic features associated with cidofovir treatment failure. Pat ients and Methods: Clinical resistance to intravitreal cidofovir was e xamined in 64 patients with CMV retinitis who received at least 1 inje ction of 20 mu g of cidofovir. Histopathologic examination, culture, a nd polymerase chain reaction were used to detect CMV in ocular specime ns. Antiviral resistance was assessed by plaque reduction assay and DN A sequencing. Results: Clinical resistance to intravitreal cidofovir i njections was identified in 3 patients (5%) and was associated with pr ior oral ganciclovir or intravenous cidofovir use. Ganciclovir- and ci dofovir-resistant CMV isolates were cultured from 2 patients and harbo red resistance-associated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous . In 1 patient, different resistance mutations were identified in ocul ar vs extraocular CMV strains. Conclusions: Clinical failure of intrav itreal cidofovir occurs infrequently, but may be associated with cidof ovir-resistant CMV selected by prior ganciclovir or cidofovir treatmen t. Ocular CMV disease can result from a localized infection with a res istant CMV strain, and antiviral resistance may develop at a local sit e of infection independently from resistance that develops systemicall y.