title: Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients: A single-center experience.
abstract: The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV.
  
  
  
  We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application.
  
  
  
  Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD.
  
  
  
  Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Danielle
authors: D
authors: El-Haddad
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA. Electronic address: elchaer.firas@gmail.com.
authors: Firas
authors: F
authors: El Chaer
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Jackapat
authors: J
authors: Vanichanan
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Dimpy P
authors: DP
authors: Shah
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Ella J
authors: EJ
authors: Ariza-Heredia
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Victor E
authors: VE
authors: Mulanovich
authors: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Alison M
authors: AM
authors: Gulbis
authors: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Elizabeth J
authors: EJ
authors: Shpall
authors: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: rfchemaly@mdanderson.org.
authors: Roy F
authors: RF
authors: Chemaly
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006561:Herpes Simplex / Q000188:drug therapy; D006566:Herpesviridae Infections / Q000188:drug therapy*; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000276:immunology / Q000821:virology; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine
keywords: Brincidofovir; Cancer; Cytomegalovirus; Herpes simplex virus; Resistance