valacyclovir and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

Brincidofovir (BCV) is a broad-spectrum antiviral agent active in vitro against double-stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir- and cidofovir-resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft-versus-host disease who was intolerant to foscarnet.

Topics: Acyclovir; Adult; Antibiotic Prophylaxis; Antineoplastic Agents; Antiviral Agents; Cytosine; Drug Resistance, Viral; Drugs, Investigational; Female; Foscarnet; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Investigational New Drug Application; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Organophosphonates; Transplantation, Homologous; Valacyclovir; Valine

Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving acyclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were acyclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valacyclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.

Topics: Acute Disease; Acyclovir; Adolescent; Amino Acid Substitution; Antiviral Agents; Bone Marrow Transplantation; Child; Cidofovir; Codon; Cytosine; DNA Mutational Analysis; Drug Resistance, Viral; Female; Foscarnet; Graft vs Host Disease; Herpes Simplex; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Mutation, Missense; Organophosphonates; Organophosphorus Compounds; Point Mutation; Salvage Therapy; Simplexvirus; Thymidine Kinase; Transplantation, Homologous; Valacyclovir; Valine; Viral Proteins; Virus Activation