Viral sensitivity testing in patients with cytomegalovirus retinitis clinically resistant to foscarnet or ganciclovir

PURPOSE: Resistance to antiviral therapy is a potential cause of progression of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We investigated the results of vital sensitivity testing in a series of patients with clinically resistant retinitis who had positive results of blood or urine cytomegalovirus cultures. METHODS: All patients with newly diagnosed cytomegalovirus retinitis between January 1990 and December 1991 were prospectively studied. Blood and urine cultures for cytomegalovirus were obtained in a nonrandomized subgroup of this group. The results of in vitro sensitivity to foscarnet and ganciclovir, determined by a DNA hybridization assay, were then analyzed in seven patients with clinically resistant cytomegalovirus retinitis and whose blood or urine culture results, or both, were positive for cytomegalovirus while on a treatment regimen. RESULTS: Foscarnet-resistant cytomegalovirus (ID₅₀ > 300 μM) was isolated from two patients, one of whom was being treated with foscarnet. Ganciclovir- resistant cytomegalovirus (ID₅₀ > 6.0 μM) was isolated from four patients, three of whom were being treated with ganciclovir. Foscarnet- and ganciclovir-resistant cytomegalovirus occurred with previous ganciclovir therapy in one patient. Clinical improvement occurred in three patients whose change in therapy was based on viral sensitivity testing. In general, prolonged therapy with one drug was associated with a progressive increase in the ID₅₀ for that drug. CONCLUSIONS: Viral resistance to foscarnet or ganciclovir may explain refractory cytomegalovirus retinitis in some patients.