A Study of Foscarnet Plus Ganciclovir in the Treatment of Cytomegalovirus of the Eye in Patients With AIDS Who Have Already Been Treated With Ganciclovir

Summary

To examine the safety and tolerance of the administration of ganciclovir and foscarnet given together or alternately; to determine the interactive pharmacokinetics (blood level) profile of long-term combined and alternating therapy with these two drugs. Additional objectives are to examine the effect of these treatments in controlling time to cytomegalovirus (CMV) retinitis progression and to examine the antiviral activity of combined and alternating ganciclovir/foscarnet treatment and development of antiviral resistance. Sight-threatening CMV retinitis occurs in at least 6 percent of AIDS patients. By 1991 (US), there may be 6000 to 10000 patients with CMV retinitis. Many clinical reports suggest that both ganciclovir (DHPG) and foscarnet have an antiviral effect against CMV that is often associated with clinical stabilization. Effectiveness of ganciclovir and foscarnet is correlated with weekly maintenance and since toxicity is dose-limiting in up to 20 percent of patients receiving either drug for long periods, it may be beneficial in long-term maintenance treatment to combine or alternate these two drugs at a lower total weekly dose of each drug. This strategy may result in a greater net antiviral effect with less toxicity than is seen with either drug alone, because the toxicities of each drug are quite different.

Timeline

Start

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Primary completion

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Completion

1993-06

Publications

• Background Jacobson MA, Kramer F, Bassiakos Y, Hooton T, Polsky B, Geheb H, O'Donnell JJ, Walker JD, Korvick JA, van der Horst C. Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151. J Infect Dis. 1994 Jul;170(1):189-93. doi: 10.1093/infdis/170.1.189.
• Background Aweeka FT, Gambertoglio JG, Kramer F, van der Horst C, Polsky B, Jayewardene A, Lizak P, Emrick L, Tong W, Jacobson MA. Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis. Clin Pharmacol Ther. 1995 Apr;57(4):403-12. doi: 10.1016/0009-9236(95)90209-0.

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