Current drugs with activity against HHV-6
In Vitro Activity against HHV-6
|Cytovene, Valcyte||HCMV||Moderate||Yes||Bone Marrow Suppression|
|Vistide||HCMV||Good||No (a)||Renal Toxicity|
lipid tagged cidofovir (IV)
Phase II Trials
|IV Brincidofovir(CMX001)**||DNA Viruses||Excellent||Yes (b)||Minimal (Low Dose)|
Phase II Trials
|Viralym M||AdV, BKV, CMV, EBV, HHV-6||Excellent||Yes||None|
(a) The product insert for Vistide states that the compound does not efficiently cross the BBB, but data is limited to one unpublished case report
(b) According to Chimerix, animal studies show that there is much greater penetration to the brain and organs than with the oral formulation.
Because of the many limitations discussed above, there is a great need for the development of novel antivirals to more effectively treat acute HHV-6 infections and reactivation. Several other compounds in various stages of clinical development have also shown effectiveness against HHV-6 in vitro (Table). More information regarding select compounds featured in this list can be found below.
|Potential anti-HHV-6 agents of the future|
|Stage of Clinical Development/ Availability||Compound name||Developing company or Laboratory||Intended use||FDA approval/ development phase||In vitro efficacy against HHV-6|
|Approved in many countries.||Artesunate**||Guilin Pharm. Co. (China), Saokim Ltd. (Int’l)||Acute malaria||CDC IND approval in the USA||Very good|
|In pharmaceutical development|
|Ampligen||Hemispherx Biopharma (USA)||CFS||Good|
|Cyclopropavir||Microbiotix, Inc (USA)||CMV, other herpesviruses||Completed Phase I||Excellent|
|Showed efficacy in laboratory testing|
|Epiphany Biosciences (USA)||VZV (Shingles); EBV (infectious mononucleosis||FDA Phase IIB trial for VZV, IIA trial for EBV.||Good|
|S2242||Hoechst (Germany)||Many herpesviruses||N/A||Good|
|Arylsulfone derivatives||Rega Institute (Belgium)||betaherpesviruses||N/A||Good|
|ZSM Derivatives||Wayne St. University of Medicine||CMV and other herpesviruses||N/A||Moderate|
|BDCRB||University of Michigan-Glaxo Wellcome, Inc. (USA)||CMV||N/A||Moderate|
|A-5021||Ajinomoto Co, Inc. (Japan)||HSV||N/A||Moderate|
|a) FDA approval rating and trial stage reported by the United States’ Food and Drug Administration (FDA) as of July 2013|
Viracyte has licensed a novel technique from Baylor College of Medicine’s Center for Cell and Gene Therapy. The Baylor group was able to generate “off the shelf” antiviral T cells for the treatment of five opportunistic viral infections, one of which was HHV-6, and this therapy has proven to be extremely effective in small trials. Their novel therapy can treat five viruses (AdV, EBV, CMV, BKV, and HHV6) representing the most frequent causes of viral morbidity and mortality in immune-compromised patients following stem cell transplantation.
This technique, called “adoptive transfer of virus-specific T cells (VSTs),” can be safe and effective, and offers many advantages over conventional antiviral treatment options because there is no toxicity and it can be used for patients infected with strains that are resistant to commonly used antivirals. Unfortunately, the cells themselves have historically been complex to prepare and limited in their antiviral range. However, after years of work that included development of an enhanced adoptive T cell immunotherapy specific to HHV-6B, as well as refining an immunotherapy technique for limiting the effects of EBV and a set of eleven viruses known to cause complications following hematopoietic stem cell transplantation (HSCT), this group’s novel approach now demonstrates the feasibility and clinical utility of rapidly generated single-culture VSTs. This therapeutic approach of isolating, treating and injecting patients with T cells may eventually prove to be the safest and most cost-effective alternative for patients with severe viral infections.
Key Resources: HHV-6 Treatment
- Baylor’s immunotherapy technique found effective in a small clinical trial…
- HHV-6 saliva DNA levels in chemotherapy patients lowered by mushroom extract…
- French dermatologists call for antiviral therapy in DRESS…
- Chimerix “SUPPRESS” trial to be largest ever for HHV-6 treatment…
- Valganciclovir shows promise during first randomized clinical trial for treatment of HHV-6 & EBV in CFS patients…
- Steroids increase HHV-6 but reduce EBV viral loads in DIHS/DRESS…
- CFS patients with ciHHV-6 may benefit from antiviral treatment…
- Successful use of Artesunate to treat HHV-6B myocarditis in a child…
- CMX001 shows strong in-vitro activity against HHV-6…
- Antiviral use in transplant patients with HHV-6 encephalitis…
The establishment of formal treatment guidelines for the effective clinical management of HHV-6 is desperately needed. While the significance of HHV-6 is becoming more clearly defined in some clinical settings (CNS infections; solid organ transplant (SOT) patients; and HSCT), the specific role of HHV-6 infection or reactivation remains to be fully established. Large-scale studies are needed to obtain a more complete understanding of the clinical impact of HHV-6A and HHV-6B, and to identify more optimal therapies to manage these emerging viruses.
The HHV-6 Foundation would like to thank Dr. Lieve Naesens and Dr. Jose Montoya for their assistance in the preparation of this summary.