Cidofovir for Viral Infections in Immunocompromised Children: Guidance on Dosing, Safety, Efficacy, and a Review of the Literature

Abstract

Objective:To describe the use of cidofovir (CDV) for viral infections in immunocompromised children (IC) and provide guidance on dosing and supportive care.Data Sources:A PubMed search was conducted for literature published between 1997 and January 2022 using the following terms: cidofovir, plus children or pediatrics.Study Selection and Data Extraction:Limits were set to include human subjects less than 24 years of age receiving intravenous (IV) or intrabladder CDV for treatment of infections due to adenovirus, polyomavirus-BK (BKV), herpesviruses, or cytomegalovirus.Data Synthesis:Data were heterogeneous, with largely uncontrolled studies. Conventional dosing (CDV 5 mg/kg/dose weekly) was commonly used in 60% (31/52) of studies and modified dosing (CDV 1 mg/kg/dose 3 times/week) was used in 17% (9/52) of studies, despite being off-label. Nephrotoxicity reported across studies totaled 16% (65/403 patients), which was higher for conventional dosing 29 of 196 patients (15%) than modified dosing 1 of 27 patients (4%). Saline hyperhydration and concomitant probenecid remain the cornerstones of supportive care, while some regimens omitting probenecid are emerging to target BKV.Relevance to Patient Care and Clinical Practice:To our knowledge, this is the first comprehensive review of CDV use (indications, dosing, supportive care, response, and nephrotoxicity) in pediatric IC.Conclusions:Effective utilization of CDV in IC remains challenging. Further prospective studies are needed to determine the optimal CDV dosing; however, less aggressive dosing regimens such as modified thrice weekly dosing or low dosing once weekly omitting probenecid to enhance urinary penetration may be reasonable alternatives to conventional dosing in some IC.