Lessons Learned From a Randomized Study of Oral Valganciclovir Versus Parenteral Ganciclovir Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients: The VICTOR Trial.
Asberg A, Humar A, et al.Clinical Infectious Diseases 2016; 62(9): 1154-1160.
Aims
To summarise and review the analysis from the VICTOR*data set which compared intravenous ganciclovir and oral valganciclovir treatment of cytomegalovirus (CMV) disease in solid organ transplant recipients.
Interventions
In the VICTOR study, participants were randomized to 21 days of intravenous ganciclovir or oral valganciclovir, followed by 4 weeks of once-daily valganciclovir secondary prophylaxis.
Participants
321 adult solid organ transplant recipients with proven CMV disease.
Outcomes
Measured outcomes included the immunosuppressive load, viral load, recurrence rate, polymorphisms and inflammatory markers.
Follow-up
1 year
CET Conclusions
This study presents some post hoc analyses from the original VICTOR study which showed comparable efficacy of treatment with intravenous ganciclovir and oral Valganciclovir for cytomegalovirus (CMV) disease in solid organ transplant recipients. Oral therapy is now the recommended treatment in clinical practice. The VICTOR biobank was used in a series of post hoc analyses to investigate other aspects that might influence the outcome of CMV disease. One of the factors that influenced outcome was the load of immunosuppression, namely dual versus triple immunosuppressive therapy and there was better outcome in the dual therapy patients. Furthermore, those patients with lower blood concentrations of CNI had more rapid CMV DNA eradication. The most significant factor influencing treatment outcome was successful eradication after three weeks of treatment. However, the authors point out that the 21 day treatment is not “one size fits all†and with higher baseline viral loads there is need for longer treatment. There is also a genetic variation in CMV that contributes to resistance. They also were able to genotype CMV isolates and half of the patients had mixed infections with two or more strains of CMV. They did not find any association between CMV load and tissue invasive disease in their study. However, they point out that this might reflect clinical practice and the reluctance to obtain biopsy evidence of CMV infection. Many other observations have been made from this post hoc analysis and the authors point out several important messages. 1. It is important to measure viral load at the outset and before stopping therapy. 2. The treatment regimen should be individualised according to CMV DNAemia. 3. Screening for mutations is necessary only for patients whose PCR levels do not follow the predicted course. 4. Effective treatment is essential to prevent emergence of resistant strains.
Quality notes
Quality assessment not appropriate for this paper *Gullestad L, et al. Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial. Transplantation 2010; 89: 864.
Trial registration
None