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Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis in patients with AIDS
M A Jacobson1, W L Drew, J Feinberg
1Department of Medicine, University of California, San Francisco.
Abstract:
Infections caused by cytomegalovirus (CMV) resistant in vitro to ganciclovir, defined as requiring greater than 6 mumols of ganciclovir for ED50 have developed in some AIDS patients with progressive CMV retinitis despite chronic ganciclovir therapy. Two such patients (CMV isolates ED50, 9.5-14.5 mumols) were treated with foscarnet, an antiviral pyrophosphate analogue to which both patients' isolates demonstrated in vitro susceptibility (ED50, less than or equal to 300 mumols). Each patient had documented retinitis progression, at 2- and 1- to 5-week intervals, respectively, despite high-dose intravenous ganciclovir therapy. Both patients responded to foscarnet therapy with cessation of viral shedding in urine and blood. After foscarnet therapy was started, retinitis stabilized in the two patients for 12 and 25 weeks, respectively, before progression recurred. Therefore, foscarnet may be effective in immunocompromised patients with rapidly progressive CMV retinitis whose CMV isolates have developed in vitro resistance to ganciclovir.
Insights
Foscarnet effectively treated cytomegalovirus (CMV) retinitis in AIDS patients resistant to ganciclovir. This antiviral therapy halted viral shedding and stabilized retinitis, offering a new option for resistant CMV infections.
Area of Science:
- Virology
- Ophthalmology
- Immunology
Background:
- Cytomegalovirus (CMV) retinitis is a serious complication in AIDS patients.
- Ganciclovir resistance in CMV isolates complicates treatment of progressive CMV retinitis.
- High-dose intravenous ganciclovir therapy failed to halt retinitis progression in two AIDS patients.
Observation:
- Two AIDS patients with progressive CMV retinitis exhibited CMV isolates resistant to ganciclovir in vitro.
- Despite high-dose ganciclovir, retinitis progression continued.
- CMV isolates showed in vitro susceptibility to foscarnet.
Findings:
- Foscarnet therapy led to cessation of viral shedding in urine and blood for both patients.
- Retinitis stabilization was observed for 12 and 25 weeks after initiating foscarnet.
- Recurrence of retinitis progression was noted after the stabilization period.
Implications:
- Foscarnet demonstrates potential efficacy in treating ganciclovir-resistant CMV retinitis in immunocompromised individuals.
- This study highlights foscarnet as a viable therapeutic option for advanced, resistant CMV infections.
- Further research is warranted to optimize foscarnet treatment protocols for CMV retinitis.