title: How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients.
abstract: Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV.
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX; and.|Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Firas
authors.initials: F
authors.lastname: El Chaer
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Dimpy P
authors.initials: DP
authors.lastname: Shah
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Roy F
authors.initials: RF
authors.lastname: Chemaly
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000401:mortality / Q000628:therapy; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D013601:T-Lymphocytes; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase