Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI –14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half‐lives and median time to eradication (21 vs. 19 days, p = 0.076). Side‐effects and discontinuations of assigned treatment (18 of 321 patients) were comparable.

[1]  R. Willemze,et al.  Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients , 2006, Bone Marrow Transplantation.

[2]  B. Alexander,et al.  Efficacy and Safety of Valganciclovir vs. Oral Ganciclovir for Prevention of Cytomegalovirus Disease in Solid Organ Transplant Recipients , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[3]  J. Itskovitz‐Eldor,et al.  Human embryonic stem cells: A potential source for cellular therapy , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  D. Dunn,et al.  Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients. , 1999, Transplantation.

[5]  H. Rollag,et al.  Cytomegalovirus DNA concentration in plasma predicts development of cytomegalovirus disease in kidney transplant recipients. , 2002, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[6]  A. Burroughs,et al.  Kinetics of cytomegalovirus load decrease in solid-organ transplant recipients after preemptive therapy with valganciclovir. , 2005, Journal of Infectious Diseases.

[7]  M. Degli-Esposti,et al.  The interplay between host and viral factors in shaping the outcome of cytomegalovirus infection , 2007, Immunology and cell biology.

[8]  V. Emery,et al.  Management of CMV infection and disease in transplant patients. 27-29 February 2004. , 2004, Herpes : the journal of the IHMF.

[9]  H. Rollag,et al.  A PROSPECTIVE STUDY OF THE NATURAL COURSE OF CYTOMEGALOVIRUS INFECTION AND DISEASE IN RENAL ALLOGRAFT RECIPIENTS1 , 2000, Transplantation.

[10]  M. van der Giessen,et al.  Prediction of recurrent cytomegalovirus disease after treatment with ganciclovir in solid-organ transplant recipients. , 1993, Transplantation.

[11]  Deepali Kumar,et al.  Cytomegalovirus (CMV) glycoprotein B genotypes and response to antiviral therapy, in solid-organ-transplant recipients with CMV disease. , 2003, The Journal of infectious diseases.

[12]  J. Preiksaitis,et al.  Canadian Society of Transplantation Consensus Workshop on Cytomegalovirus Management in Solid Organ Transplantation Final Report , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  D. Lilleri,et al.  Monitoring of Human Cytomegalovirus‐Specific CD4+ and CD8+ T‐Cell Immunity in Patients Receiving Solid Organ Transplantation , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  Guy Boivin,et al.  Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid-organ transplant patients with CMV disease. , 2002, The Journal of infectious diseases.

[15]  A. Caliendo,et al.  Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients. , 2000, Journal of clinical microbiology.

[16]  S. Walmsley,et al.  A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitis. , 2002, Journal of acquired immune deficiency syndromes.

[17]  A. Humar,et al.  American Society of Transplantation Recommendations for Screening, Monitoring and Reporting of Infectious Complications in Immunosuppression Trials in Recipients of Organ Transplantation , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[18]  Daniel F. Martin,et al.  A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. , 2002, The New England journal of medicine.

[19]  J. Gómez-Moreno,et al.  Infection in organ-transplant recipients. , 1998, The New England journal of medicine.

[20]  T. F. Smith,et al.  Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. , 2000, The Journal of infectious diseases.

[21]  J. Rabkin,et al.  Valganciclovir Results in Improved Oral Absorption of Ganciclovir in Liver Transplant Recipients , 2000, Antimicrobial Agents and Chemotherapy.

[22]  Risto S. Cvetković,et al.  Valganciclovir , 2012, Drugs.

[23]  Barbara Alexander,et al.  Pharmacokinetic Profile of Ganciclovir After its Oral Administration and From its Prodrug, Valganciclovir, in Solid Organ Transplant Recipients , 2005, Clinical pharmacokinetics.

[24]  Thomas F. Smith,et al.  Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir. , 2003, The Journal of infectious diseases.

[25]  D. Jung,et al.  Single‐Dose Pharmacokinetics of Valganciclovir in HIV‐ and CMV‐Seropositive Subjects , 1999, Journal of clinical pharmacology.

[26]  M. Pescovitz Valganciclovir: what is the status in solid organ transplantation? , 2006 .