title: Observations on the use of cidofovir for BK virus infection in renal transplantation.
abstract: BACKGROUND
  In renal transplantation, BK virus infection can result in significant graft nephropathy and loss. While reduction in immunosuppression (IS) is considered standard therapy, adjunct agents may be warranted. Data are suggestive of a possible role of cidofovir for the management of BK. This study aims to describe the course of BK viremia (BKV) in a large cohort of renal transplant patients receiving adjunct cidofovir.
  
  
  METHODS
  We evaluated kidney and kidney-pancreas recipients who received cidofovir combined with reduced IS for management of high-level BKV or BK virus nephropathy (BKVN). We examined the rate and timing of BKV clearance, and performed a multivariate analysis to identify risk factors associated with long-term (>6 months) viremia.
  
  
  RESULTS
  In total, 75 patients received a median of 13 doses of cidofovir in conjunction with reduced IS; 32 patients (43%) had short-term BKV (≤6 months), and 43 (57%) had long-term BKV. Overall, 53 of 75 patients (71%) eventually cleared BKV at a median of 4.2 months (interquartile range 2.1-9.3 months). Independent factors associated with long-term BKV included older age (odds ratio [OR] 1.1, P = 0.02), delayed graft function (OR 31.4, P = 0.01), and higher peak BKV (OR 12.8, P = 0.02), while BKV reduction by at least 1 log(10) copies/mL at 1 month of treatment was associated with clearance within 6 months (OR 49.3, P < 0.01). Patients with earlier clearance maintained stable graft function and no graft losses, while long-term BKV was associated with a 15% decline in estimated glomerular filtration rate.
  
  
  CONCLUSIONS
  Adjunct cidofovir resulted in preservation of renal function when viral clearance occurred within 6 months of initiation. This retrospective review defines factors predicting response to cidofovir in conjunction with reduced IS for BKVN or high-level BKV. Still, considering cost, frequency of administration, and treatment duration, a randomized trial is necessary to define the exact utility of cidofovir in the setting of BK virus infection.
authors.affiliation: Department of Pharmacy, Houston Methodist J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Kuten
authors.forename: S J
authors.initials: SJ
authors.lastname: Patel
authors.forename: R J
authors.initials: RJ
authors.lastname: Knight
authors.forename: L W
authors.initials: LW
authors.lastname: Gaber
authors.forename: J M
authors.initials: JM
authors.lastname: DeVos
authors.forename: A O
authors.initials: AO
authors.lastname: Gaber
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001739:BK Virus; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000188:drug therapy* / Q000821:virology; D012189:Retrospective Studies; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D014766:Viremia
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: BK virus; antiviral; cidofovir; renal transplantation