cmx-001 and Herpes-Zoster

The mainstay of antiviral therapy for the alpha-herpesviruses [herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV)] over the past 40 years has been the nucleoside analogues such as aciclovir. Although conventional antiviral therapy has reduced mortality in severe disease, novel agents are needed to address the emergence of resistance and toxicity associated with current second-line therapy. Treatment and prophylaxis of VZV and HSV reactivations remains a challenge.. A number of compounds have recently been evaluated in human clinical trials, amongst them brincidofovir, an intracellularly acting derivative of cidofovir currently undergoing phase III trials. The helicase-primase inhibitors are a new class of antiviral agent and may circumvent resistance to existing agents. Amenamevir and pritelivir are two examples of these agents that have been evaluated clinically along with novel nucleoside analogues such as valomaciclovir and FV-100. Tenofovir, an agent used in HIV and hepatitis B therapy, may also have a role in the prevention of HSV-2 acquisition and reduce viral shedding.. Although several novel antiviral agents have undergone clinical trials in recent years, all are yet to gain licensure. Brincidofovir appears to be the candidate with most promise for adoption into routine practice in the near future.

Topics: Antiviral Agents; Clinical Trials as Topic; Cytosine; Drug Discovery; Drug Evaluation; Drug Resistance, Viral; Herpes Simplex; Herpes Zoster; Humans; Microbial Sensitivity Tests; Organophosphonates; Treatment Outcome; Virus Replication

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

Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.

Topics: Acyclovir; Adenoviridae; Adenovirus Infections, Human; Antibiotic Prophylaxis; Antiviral Agents; Child, Preschool; Cidofovir; Cytosine; DNA, Viral; Drug Resistance, Viral; Epstein-Barr Virus Infections; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpes Zoster; Herpesvirus 1, Human; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Immunocompromised Host; Meningoencephalitis; Mucositis; Myelodysplastic Syndromes; Organophosphonates; Rituximab; Viral Load