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Valganciclovir (VGCV) vs. IV Ganciclovir (GCV) as Induction Therapy for Newly Diagnosed Cytomegalovirus (CMV) Retinitis: A Randomized, Controlled Study D. MARTIN*, J. SIERRA-MADERO, S. WALMSLEY, R. WOLITZ, F. BROWN, and C. ROBINSON for the Roche Valganciclovir Study Group.
Roche Global Development, Palo Alto, CA Background: Valganciclovir is an orally bioavailable monovalyl ester prodrug that is rapidly hydrolyzed to the active nucleoside analogue ganciclovir. The bioavailability of GCV from VGCV is 60% and 900 mg of VGCV provides a GCV exposure (AUC) comparable to IV GCV 5 mg/kg.
Methods: We studied the safety and efficacy of VGCV 900 mg bid x 3 weeks followed by 900 mg qd compared to that of IV GCV 5 mg/kg bid x 3 weeks followed by 5 mg/kg daily qd for the induction treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. The primary efficacy endpoint was photographically determined CMV retinitis progression within 4 weeks of initiating treatment. Secondary endpoints included the achievement of a prospectively defined "satisfactory response" to induction therapy and the time to progression of CMV retinitis. Pharmacokinetic (PK) profiles were obtained at weeks 1 (induction dosing) and 4 (maintenance dosing).
Results: The two treatment groups were balanced with regard to CD4 count and HAART use. An equivalent number (7) and proportion (10%) in each group progressed during the first 4 weeks. Seventy -seven percent and 72% of evaluable patients in the IV GCV and VGCV groups respectively achieved the prospectively defined "satisfactory" response to induction therapy at 4 weeks. Median (mean) times to first CMV retinitis progression were 120 (210) days in the IV GCV induction group and 198 (226) days in the VGCV induction group. Prospectively defined subset analyses confirmed that the therapeutic response was similar in both treatment arms when analyzed by baseline and week 4 CD4 counts, rise in CD4 counts and HAART use. Mean (±SD) AUCs for each treatment were similar at both induction (VGCV 32.8±10.1 vs. GCV 28.6±9.0 mg.h/mL) and maintenance doses (VGCV 34.9±13.3 vs. GCV 30.7±7.7 mg.h/mL). Absolute bioavailability of GCV from VGCV was confirmed as 60% in AIDS patients with CMV retinitis. Adverse event frequency and severity were similar among treatment groups.
Conclusion: Valganciclovir, an oral prodrug of ganciclovir with high bioavailability, provides a convenient and effective alternative to IV ganciclovir for the treatment of CMV retinitis.
Key Words: cytomegalovirus, retinitis, valganciclovir
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