What is the recommended treatment for HHV6 (Human Herpesvirus 6) infections?

Treatment of Human Herpesvirus 6 (HHV-6) Infections

For HHV-6 infections causing clinical disease, foscarnet (90 mg/kg twice daily) or ganciclovir (5 mg/kg twice daily) are the recommended first-line treatment options, with foscarnet showing better outcomes in terms of response rates and mortality, particularly in immunocompromised patients. 1, 2

Diagnosis and Confirmation

• Diagnosis of active HHV-6 infection should be confirmed by:
  • PCR detection of HHV-6 DNA in cerebrospinal fluid (for encephalitis)
  • PCR detection in plasma (not whole blood) for systemic infection
  • Exclusion of chromosomally integrated HHV-6 (ciHHV-6), which occurs in ~1% of the population 2, 3

Treatment Algorithm

First-line Treatment Options:

1. Foscarnet:

   • Dosage: 90 mg/kg IV twice daily (180 mg/kg/day)
   • Better response rates (93% with full dose vs. 74% with lower doses)
   • Associated with lower 30-day mortality in transplant patients
   • Main adverse effects: nephrotoxicity and electrolyte disturbances 2, 1

2. Ganciclovir:

   • Dosage: 5 mg/kg IV twice daily (10 mg/kg/day)
   • Response rate: 84% with full dose vs. 58% with lower doses
   • Main adverse effect: myelosuppression (bone marrow toxicity) 2, 1

Treatment Duration:

• Continue treatment for at least 3 weeks
• Continue until HHV-6 DNA is cleared from blood and, if possible, CSF 1

Special Situations:

1. Severe or Refractory Cases:

   • Consider combination therapy with foscarnet and ganciclovir
   • One study reported 100% response rate with combination therapy, though sample size was small 2

2. Treatment Failure:

   • Consider cidofovir as a third-line option, though data are limited
   • Check for development of antiviral resistance 2
   • Consider switching classes of antiviral medications (e.g., from ganciclovir to foscarnet) 2

3. Immunocompromised Patients:

   • Prioritize foscarnet due to better outcomes in this population
   • Consider reducing immunosuppressive medications when possible 1

Specific Clinical Scenarios

HHV-6 Encephalitis:

• Most common in hematopoietic stem cell transplant recipients
• Initiate treatment immediately upon strong suspicion
• Foscarnet is preferred due to better CNS penetration and lower mortality 2, 1

HIV-Infected Patients:

• If disease is determined to be caused by HHV-6, use ganciclovir or foscarnet with treatment schedules similar to those used for CMV disease 2

Prevention and Prophylaxis

• HHV-6 is ubiquitous, and prevention of exposure is not feasible 2
• Routine screening of HHV-6 DNA in blood post-HSCT is not recommended 2
• Prophylactic or pre-emptive anti-HHV-6 therapy is not recommended due to lack of proven efficacy 2

Emerging Therapies

• Brincidofovir (CMX-001) shows high activity against HHV-6 in vitro but has significant gastrointestinal toxicity 2
• Adoptive immunotherapy with virus-specific T cells is a promising approach that appears safe and potentially effective in small studies 2, 4

Monitoring During Treatment

• Monitor renal function and electrolytes, particularly with foscarnet
• Follow viral load in blood and, if applicable, CSF
• Watch for drug-specific toxicities (nephrotoxicity with foscarnet, myelosuppression with ganciclovir)

Important Caveats

• Mutations conferring resistance to antivirals have been described but are rare in clinical practice 2
• The indications for treatment of HHV-6 infection in many patient populations remain unclear due to the difficulty in establishing causality between infection and disease 3, 5
• Controlled studies on HHV-6 treatment are limited, and formal approval for specific indications is lacking 3, 6