Efficacy of brincidofovir as prophylaxis against HSV and VZV in hematopoietic cell transplant recipients

Transpl Infect Dis. 2018 Dec;20(6):e12977. doi: 10.1111/tid.12977. Epub 2018 Sep 3.

Abstract

Allogeneic hematopoietic cell transplant (HCT) recipients are at risk for herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Routine prophylaxis with acyclovir is recommended during periods of immunosuppression. Brincidofovir (BCV, CMX001), a lipid conjugate of cidofovir, has shown in vitro activity against HSV/VZV, but has not been formally studied for HSV/VZV prophylaxis. We report our clinical experience of BCV for HSV/VZV prophylaxis in HCT recipients. This was a retrospective review of 30 hematopoietic cell transplant (HCT) recipients between 8/2010 and 8/2015 who received BCV doses not exceeding 200 mg/week for adults/adolescents and 4 mg/kg/week for pediatric (<12 years) patients, for ≥14 days BCV without concomitant acyclovir under clinical trials or single patient use. HSV/VZV cases during BCV treatment were confirmed by viral culture or PCR and clinical symptoms. Of 30 patients who met the inclusion criteria, 27 (90%) patients were adults and 22 (73%) patients received T-cell depleted HCT. The most common indications for BCV were cytomegalovirus in 12 patients (40%) and adenovirus in 11 patients (37%). One patient was treated for acyclovir-resistant HSV and one for disseminated VZV. There were two breakthrough cases of HSV infection during 2170 patient-days. There were no cases of breakthrough VZV infection. The overall rate of breakthrough HSV infection was 1.0 per 1000 patient-days, without any breakthrough VZV infections. Our study provides the only available-albeit limited-evidence on the potential efficacy of BCV for HSV/VZV prophylaxis in HCT patients. Additional studies are needed to further assess the efficacy and safety of BCV in the setting.

Keywords: brincidofovir; hematopoietic cell transplant; herpes simplex virus (HSV); varicella-zoster virus (VZV).

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antibiotic Prophylaxis / methods*
  • Child
  • Child, Preschool
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Cytosine / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpes Simplex / epidemiology
  • Herpes Simplex / prevention & control*
  • Herpes Simplex / virology
  • Herpesvirus 3, Human / drug effects
  • Herpesvirus 3, Human / isolation & purification
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Organophosphonates / pharmacology
  • Organophosphonates / therapeutic use*
  • Retrospective Studies
  • Simplexvirus / drug effects
  • Simplexvirus / isolation & purification
  • Treatment Outcome
  • Varicella Zoster Virus Infection / epidemiology
  • Varicella Zoster Virus Infection / prevention & control*
  • Varicella Zoster Virus Infection / virology
  • Young Adult

Substances

  • Organophosphonates
  • brincidofovir
  • Cytosine