Safety and efficacy of intravenously administered cidofovir in adult haematopoietic cell transplant recipients: a retrospective multicentre cohort study

Objectives: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods: This was a retrospective multicentre cohort study including adult HCT recipients who received >= 1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results: We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N=115; 69.7%), 1 mg/kg/week (18; 10.9%), 3mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P=0.05), weight (OR 1.05; P=0.01), CMV infection (OR 3.6; P=0.02), liposomal amphotericin B (OR 8.06; P=0.05) and IV voriconazole/posaconazole (OR 13.0; P=0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.160.95 mg/dL) compared with baseline (0.91 +/- 0.39 mg/dL; P<0.001), but improved by 2weeks (0.91 +/- 0.84 mg/dL; P=0.007) and 4 weeks (0.96 +/- 0.89 mg/dL; P=0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P<0.0001) and for patients with CMV DNAaemia by EOT+4 weeks (P=0.003), but not for patients with BK virus DNAaemia. Conclusions: One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.