HDP-CDV as an alternative for treatment of human herpesvirus-6 infections

Bonnafous, Pascale; Bogaert, Sofie; Godet, Angélique N.; Agut, Henri

doi:10.1016/j.jcv.2012.11.006

Cited by 20 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A relatively recently introduced compound, brincidofovir (1-O-hexadecyloxypropyl-cidofovir; formerly known as CMX001), is an orally bioavailable lipid conjugate of cidofovir displaying substantially less nephrotoxicity than that of the parent drug. The compound has been employed successfully for treatment of viral infections in allo-HSCT recipients and other settings (241)(242)(243), but mutations conferring resistance may arise (244). Preliminary observations on the efficacy against HAdV showed promising results (245,246), and clinical development of the drug is currently ongoing.…”

Section: Antiviral Drugsmentioning

confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

View full text Add to dashboard Cite

SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

show abstract

Section: Antiviral Drugsmentioning

confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

View full text Add to dashboard Cite

show abstract

“…Brincidofovir, also known as CMX001, is an orally administered lipid-ester derivative of cidofovir which is active against numerous DNA viruses, including HHV-6, is detected at significant levels in CSF from treated patients, and is less toxic for the kidney than cidofovir (137,204,211). Artesunate is a derivative of artemisinin, a drug used for the treatment of malaria.…”

Section: Antiviral Agentsmentioning

confidence: 99%

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

2015

Self Cite

View full text Add to dashboard Cite

SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.

show abstract

“…15 Many other compounds that are active against cytomegalovirus, including brincidofovir (CMX-001), 78,79 CMV423, 80 methylenecyclopropane analogs 81 and artesunate 82 have also been reported to inhibit HHV-6 in vitro. Administration of brincidofovir at a single dose of 2 mg/kg led to maximum plasma concentrations of 350 ng/mL 83 that sufficiently exceeds the half-maximum effective concentration of HHV-6B strain 79 without adverse events including changes in hematological or renal functions. 83 A case report showed artesunate was effective and safe for treating HHV-6B myocarditis.…”

Section: Hhv-6 Encephalitis After Allo-hct M Ogata Et Almentioning

confidence: 99%

“…The results of this study are encouraging because they may indicate the effect of currently available agents for high-risk patients, but we also consider that toxicity of PFA limits the practical application of prophylaxis to the wider HCT recipient population. Many other new compounds including brincidofovir, 78,79 methylenecyclopropane analogs 81 or artesunate 82 may be available in the future for preventing HHV-6 encephalitis. A phase 2 trial showed that brincidofovir effectively prevented cytomegalovirus diseases without myelosuppression and nephrotoxicity in allo-HCT recipients.…”

Section: Prevention: We Do Not Know Measures For Preventing Hhv-6 Encmentioning

confidence: 99%

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Ogata

Fukuda²,

Teshima

2015

Bone Marrow Transplant

107

View full text Add to dashboard Cite

Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after umbilical cord blood transplantation, typically around 2-6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication.

show abstract

HDP-CDV as an alternative for treatment of human herpesvirus-6 infections

Cited by 20 publications

References 10 publications

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Contact Info

Product

Resources

About