What is the immediate treatment recommendation for patients with MRI findings suggestive of JC virus or Human Herpesvirus 6 (HHV-6) infections?

From the Guidelines

The immediate treatment recommendation for patients with MRI findings suggestive of JC virus or Human Herpesvirus 6 (HHV-6) infections is to initiate intravenous ganciclovir (5 mg/kg every 12 hours) or foscarnet (90 mg/kg every 12 hours) for HHV-6 encephalitis, while for JC virus, restoring immune function by withdrawing immunosuppressive medications is the primary intervention. For JC virus, which causes Progressive Multifocal Leukoencephalopathy (PML), there is no specific antiviral therapy proven effective against JC virus 1. The primary intervention is to restore immune function by withdrawing immunosuppressive medications when possible. For patients on immunomodulatory drugs like natalizumab, immediate plasma exchange to remove the medication may be warranted. For HHV-6 encephalitis, treatment with intravenous ganciclovir or foscarnet should be initiated promptly, with the recommended doses being 5 mg/kg every 12 hours for ganciclovir and 90 mg/kg every 12 hours for foscarnet 1. Treatment typically continues for at least three weeks, with monitoring of renal function and electrolytes due to potential nephrotoxicity. Some key points to consider in the treatment of HHV-6 encephalitis include:

• The use of full-dose therapy with foscarnet (≥180 mg/kg) or ganciclovir (≥10 mg/kg) is associated with a better response rate than treatment with lower doses 1
• Combined ganciclovir and foscarnet therapy can be considered, but drug toxicity is an important consideration 1
• Immunosuppressive medications should be reduced if possible 1
• Supportive care and management of increased intracranial pressure may be needed in both conditions. It's worth noting that the evidence for the treatment of HHV-6 encephalitis is based on studies in patients with hematologic malignancies or post-transplant, and may not be generalizable to other patient populations 1.

From the Research

Immediate Treatment Recommendations

For patients with MRI findings suggestive of JC virus or Human Herpesvirus 6 (HHV-6) infections, the following treatment recommendations are suggested:

• Antiviral therapy with agents such as ganciclovir, foscarnet, or cidofovir may be effective against HHV-6 infections 2, 3, 4, 5
• In cases of JC virus and HHV-6 coinfection, treatment with anti-5HT2A receptors agents and antiviral therapy may be recommended 6
• High-dose ganciclovir (18 mg/kg/day) has been used as antiviral treatment in immunocompetent children with severe HHV-6-induced encephalitis 3

Diagnostic Considerations

• The diagnosis of HHV-6 infection is performed by both serologic and direct methods, including the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR 5
• In cases of suspected JC virus and HHV-6 coinfection, research of HHV-6 and JCV should be performed on cerebrospinal fluid (CSF) and on blood samples 6
• Chromosomally integrated human herpesvirus 6 (ciHHV-6) should be excluded in case of detection of HHV-6 DNA 6

Treatment Options

• Ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment and conditions of drug administration are not formally approved to date 5
• Other antiviral compounds, such as S2242, A-5021, and cyclopropavir, are being investigated as potential treatments for HHV-6 infections 4