Virologic response with 2 different cidofovir dosing regimens for preemptive treatment of adenovirus DNAemia in pediatric solid organ transplant recipients

Abstract

ADV is frequently seen in our pediatric SOT population. It presents in a variety of clinical presentation and can cause severe disease. In this population, there are very few studies to determine the safety of CDV as a potential therapeutic agent. We present the findings of our retrospective study evaluating the efficacy and safety of CDV as 2 separate dosing regimens. Regimen A uses the standard 5 mg/kg once a week (Regimen A), and the second uses the 1 mg/kg 3 times per week (Regimen B). Overall, the dosing regimen did not differ in nephrotoxicity, but Regimen B had a higher, although non-significant, rate of viral load clearance. This suggests that more frequent dosing at lower levels may be more efficacious without any significant side effects in our SOT population.

Adjunctive Use of Cidofovir and Intravenous Immunoglobulin to Treat Invasive Adenoviral Disease in Solid Organ Transplant Recipients

“…One study of 19 pediatric SOT patients with one or more positive ADV VL PCRs, treated with cidofovir (either 5 mg/kg IV weekly for 2 weeks or 5 mg/kg every other week), described the adjunctive use of IVIG in 30% of the subjects. In that study, the use of IVIG was not found to be a significant factor in the clearance of ADV VL in covariate analysis …”

“…At our institution, patients were treated with either 3 times/week or once/week cidofovir based on provider preference. A recent study in pediatric SOT patients showed no difference in nephrotoxicity between the two cidofovir regimens; however, 3 times/week cidofovir may have a higher rate of virologic response . The AST guidelines recommend continuing cidofovir therapy until complete symptom resolution and documentation of three negative ADV samples, 1 week apart .…”

Infección grave diseminada por Adenovirus en receptores de trasplante Hepático

“…Pensamos que esto último fue lo que cambió la evolución en el segundo paciente, ya que se hizo de manera muy precoz, estando bien documentado que la mejora del estado inmunológico, principalmente el celular, es la vía de resolución de la viremia (18) . Las drogas antivirales aprobadas para el tratamiento de la enfermedad por adenovirus son el cidofovir y el brincidofovir (19,(25)(26)(27)(28) . Si bien no está aprobado el ganciclovir para el tratamiento de adenovirus, dado que existe poca evidencia clínica de su utilidad, se cuenta con reportes de actividad in vitro para este microorganismo.…”

Disseminated Adenovirus Infection After Combined Liver-Kidney Transplantation

“…Reduction in immunosuppression often becomes necessary for clearance and is generally the first step in addressing treatment (Florescu et al, 2013 ; Patel et al, 2015 ). While precise quantification of the degree of immunosuppression in SOT recipients is an area of active investigation, it is generally supported that viral activation is evidence of “over-immunosuppression.” Cidofovir is active against HAdV, but its low oral bioavailability and potential for nephrotoxicity are major dose-limiting factors (Ganapathi et al, 2016 ; Guerra Sanchez et al, 2018 ). CMX-001 is an orally bioavailable, lipid-ester derivative of cidofovir with improved intracellular active drug delivery.…”