1597. Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus (CMV) Infection and Disease in Solid Organ Transplant (SOT) Recipients
Session: Poster Abstract Session: Viruses and Bacteria in Immunocompromised Patients
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • Poster_1597_KSH.pdf (566.9 kB)
  • Background: Following solid organ transplantation (SOT), the optimal dose of primary (val)ganciclovir (v(gcv)) prophylaxis against CMV infection is debated, and breakthrough infection and treatment-limiting side effects are frequently seen. Rates and risk factors for CMV prophylaxis breakthrough and premature cessation of prophylaxis for other reasons were investigated in a large cohort of consecutive SOTs.  

     

    Methods: SOT recipients transplanted (tx) between 2012-2016 at Rigshospitalet, and who were initiated on primary prophylaxis ≤14 days post-tx were followed from this time until 90 (±7) days post-tx. A prophylaxis score for each patient/day was calculated during the follow-up time (FUT) (score of 100 corresponding to the manufacturers’ recommended dose for a given eGFR; Fig. 1). Prophylaxis breakthrough was defined as PCR verified CMV DNA positivity in plasma or BAL (i.e. infection) and premature stop of prophylaxis as >7 days with a score of 0. Time to event and hazard ratios (HR) were estimated with Cox models after adjustment for relevant risk factors.                                                                           

     

    Results: Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 41 (7%, 95% CI 4.9-9.1%) experienced CMV prophylaxis breakthrough (9/41 [22%, 9.2-34.6%] developed viral resistance to (v)gcv) and 33/585 (5.6%, 3.7-7.5%) ceased prophylaxis for other reasons during the first 90 days after tx. After adjustment for tx type, CMV IgG D+/R- mismatch and increasing % of FUT with a prophylaxis score < 90 were associated with increased risk of breakthrough (HR 4.76 [95% CI 2.38-9.54] p<0.001 and HR 1.15 [1.04 - 1.27] p=0.007/10% longer FUT w/ score < 90 respectively, Fig 2) whereas tx type was not. The main risk factor for stopping prophylaxis for reasons other than breakthrough was lung tx (22.9%, HR 13.4 (versus kidney SOT) [5.4-33.4]), mainly due to liver or myelotoxicity.

     

    Conclusion: SOTs receiving (v)gcv primary prophylaxis doses below the manufacturers’ recommended doses according to latest eGFR were at an increased risk of CMV prophylaxis breakthrough, particularly in case of CMV IgG D+/R- mismatch, while 23% of lung tx recipients stopped prophylaxis mainly due to toxicity. Our findings indicate the need to dose adjust (v)gcv according to latest eGFR and preferably use novel, less toxic agents.   

    Mark Poulsen Khurana, Medical Student, Center of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Isabelle Paula Lodding, MD, Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Amanda Mocroft, MSc, Professor, Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom, Søren Schwartz Sørensen, MD, Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Michael Perch, MD, Department of Cardiology, Section for Lung Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Allan Rasmussen, MD, Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, Finn Gustafsson, MD, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark and Jens Lundgren, MD, DMSc, Professor, Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Disclosures:

    M. P. Khurana, None

    I. P. Lodding, None

    A. Mocroft, None

    S. Schwartz Sørensen, None

    M. Perch, None

    A. Rasmussen, None

    F. Gustafsson, None

    J. Lundgren, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.