COMPLICATIONS - INFECTIONS

G.M. Scott¹, Z. Naing¹, J. Pavlovic², Z.M. Waliuzzaman¹, J. Iwasenko³, N. Rismanto¹, P. Angus², R. Jones², W.D. Rawlinson^1
1Seals, Virology, Randwick/AUSTRALIA, ², Liver Transplant Unit, Melbourne/AUSTRALIA, ³, Virology, SEALS, Randwick/AUSTRALIA

Body: Background: Antiviral agents have been available for the treatment of cytomegalovirus (CMV) disease for some time, and more recent use of valganciclovir (valGCV) for primary prophylaxis has provided a bioavailable and more easily administered alternative for prophylaxis and treatment of CMV infection. However, CMV remains a major problem for immunocompromised transplant recipients and neonates infected in utero. We addressed issues of CMV therapy relating to prophylaxis versus laboratory-guided preemptive therapy, duration of therapy and emergence of antiviral resistant strains. The emergence of antiviral resistant CMV strains in 10% of treated patients, and up to 30% of high risk groups, with the potential for cross-resistance means therapy is these patients is an emerging problem. The lack of consistent results in the use of combination therapy (ganciclovir plus foscarnet) and lack of effective new agents means CMV antiviral resistance is a significant emerging risk for transplant recipients, particularly those who are highly immunocompromised. Methods: We investigated valGCV prophylaxis versus laboratory-guided preemptive therapy for the prevention of CMV infection and disease in liver transplant recipients from the Austin Health Liver Transplant Unit in Melbourne, Australia. A well-characterised cohort of 64 patients was constructed, with patients randomly assigned into valGCV prophylaxis and observational arms. All CMV seronegative patients who received a liver from a CMV seropositive donor (D+R-) were sorted into the prophylaxis arm for ethical reasons. Virologic monitoring post-transplant was weekly blood samples for 12 weeks post-transplant for CMV viral load determination with assessment of antiviral resistance using UL97 protein kinase and UL54 DNA polymerase gene sequencing in patients with rising or persistently high viral loads after two weeks of therapy. Following this period, blood was taken monthly up to 18 months post-transplant. Clinical data were collected over this period at each clinical visit. Results and Conclusions: ValGCV prophylaxis reduced the overall incidence of active CMV infection in these patients, with persistent CMV infection occurring in 48% of patients in the observational arm and in 25% of patients who received valGCV prophylaxis. CMV-related disease was diagnosed in 8% (3/39) of patients in the prophylaxis arm, while no patients in the observational arm progressed to CMV disease. However, the majority of prolonged CMV infection and the development of disease occurred in D+R- patients, all of whom were given valGCV prophylaxis because of their high risk serostatus. Antiviral resistant CMV strains were identified in four patients, all of whom were in the prophylaxis arm and were D+R- serostatus. The emergence of CMV-related disease and antiviral resistant infections mostly occurred after the prophylaxis period, indicating that 100 days of prophylaxis was not sufficient to prevent these outcomes. Extending the prophylaxis period as a strategy to prevent late onset disease, and using laboratory-guided preemptive therapy may be appropriate in highly immunosuppressed patients.

Disclosure: All authors have declared no conflicts of interest.