Background: Treatment of GCV-resistant(GCV-R)or refractory CMV infections in hematopoietic stem cell transplant (HSCT)and solid organ transplant (SOT)recipients remains controversial.Foscarnet (FOS)and cidofovir(CDV),nucleotide analogues with activity against CMV,are both nephrotoxic.CDV is also oculotoxic.We evaluated the outcomes of patients with GCV-R or refractory CMV treated with CDV. Methods: All HSCT and SOT recipients at one center who were treated with CDV for GCV-R or refractory CMV infection between 1/1/2008 and 6/30/2015 were retrospectively evaluated.Data collection included baseline demographics,UL97 genotype mutations,CMV viremia versus disease,toxicities(renal and ocular),virologic outcomes,and 6- and 12-month mortalities.Results were evaluated with descriptive statistics. Results: 12 patients received CDV for treatment of CMV:4 HSCT/oncology and 8 SOT(5 kidney,1 heart,1 liver,and 1 lung).One patient with AIDS and lymphoma was included in the HSCT/oncology group.58.3% were women,75%had a CMV seropositive donor,and 33% of the recipients were CMV seropositive.The median time to CMV viremia was 138 days(IQR34–246 days).Tissue invasive disease was present in 50%. 83% had genotype testing,and 70% of those had UL97 ganciclovir resistance mutations.While on CDV,25% developed nephrotoxicity(defined as a 1.5x rise in serum creatinine)and 25%developed uveitis.33% had virologic failure(defined as unable to achieve two consecutive undetectable CMV viral loads at least 5 days apart)despite CDV treatment.50% of the patients died,and the median time to death was 1.08 months(IQR 0.6–14.9months).

Conclusion: Although CDV is frequently used in GCV-R and refractory CMV infection,it is associated with a substantial risk of drug toxicity and virologic failure,highlighting the need for development of newer and less toxic therapies.The high mortality in this group of patients underscores the severity of illness in this population.

CITATION INFORMATION: Mehta S, Alfares M, Valsamakis A, Shoham S, Boger R, Lees L, Ostrander D, Avery R. Outcomes of Transplant Recipients Treated with Cidofovir for Resistant or Refractory Cytomegalovirus Infection. Am J Transplant. 2016;16 (suppl 3).

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