[Selective inhibition of replication of human cytomegalovirus by desferrioxamine in vitro and in vivo (case report)].
HERMANN O.C. GÜMBEL, Jindrich Jr. Cinatl, Holger Rabenau, Jens‐Uwe Vogel, Hans Wilhelm Doerr, Christian Ohrloff
Abstract
HERMANN O.C. GÜMBEL, Jindrich Jr. Cinatl, Holger Rabenau, Jens‐Uwe Vogel, Hans Wilhelm Doerr, Christian Ohrloff
Abstract
UNLABELLED: In AIDS patients cytomegalovirus (HCMV) retinitis is one of the most frequent opportunistic infections. Antiviral therapy aims at preserving vision as long as possible, but more and more HCMV isolates are proving to be resistant to ganciclovir (GCV) and foscarnet (PFA) in vitro. We tested whether desferrioxamine (DFO), an iron chelator with antiherpetic activity, can inhibit clinical virus isolates and laboratory strains. Clinical isolates were obtained from urine samples of AIDS patients with HCMV retinitis. The concentrations of DFO required for 50% and 90% reduction of the production of HCMV in several HCMV strains ranged from 3.1 to 4.9 microns and from 14.2 to 17.3 microns, respectively, Inhibitory effects of DFO on HCMV replication were completely prevented by co-incubation with stoichiometric amounts of FE3+. CASE REPORTS: DFO was administered by daily dose of 1 g i.v. to a patient with AIDS in whom HCMV retinitis continued to progress despite combination therapy with GCV and PFA. The addition of DFO to the combination inhibited progression of the disease. No relapse of HCMV retinitis was seen with 3 months of DFO therapy. The treatment was free of side effects.
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UNLABELLED: In AIDS patients cytomegalovirus (HCMV) retinitis is one of the most frequent opportunistic infections. Antiviral therapy aims at preserving vision as long as possible, but more and more HCMV isolates are proving to be resistant to ganciclovir (GCV) and foscarnet (PFA) in vitro. We tested whether desferrioxamine (DFO), an iron chelator with antiherpetic activity, can inhibit clinical virus isolates and laboratory strains. Clinical isolates were obtained from urine samples of AIDS patients with HCMV retinitis. The concentrations of DFO required for 50% and 90% reduction of the production of HCMV in several HCMV strains ranged from 3.1 to 4.9 microns and from 14.2 to 17.3 microns, respectively, Inhibitory effects of DFO on HCMV replication were completely prevented by co-incubation with stoichiometric amounts of FE3+. CASE REPORTS: DFO was administered by daily dose of 1 g i.v. to a patient with AIDS in whom HCMV retinitis continued to progress despite combination therapy with GCV and PFA. The addition of DFO to the combination inhibited progression of the disease. No relapse of HCMV retinitis was seen with 3 months of DFO therapy. The treatment was free of side effects.
Key concepts: Retinitis, Foscarnet, Human cytomegalovirus, Ganciclovir, Cytomegalovirus retinitis, Virology, In vivo, Medicine