What is Human Herpesvirus 6 (HHV-6)?

From the Guidelines

HHV-6 infection in patients with hematologic malignancies or post-transplant should be treated with foscarnet or ganciclovir, as these antiviral medications have been shown to inhibit HHV-6 replication and improve symptoms. The treatment of HHV-6 infection is crucial in preventing morbidity and mortality, particularly in immunocompromised patients. According to the guidelines from the 2017 European Conference on Infections in Leukaemia 1, foscarnet and ganciclovir are recommended for the treatment of HHV-6 encephalitis post-hematopoietic stem cell transplant.

Some key points to consider in the treatment of HHV-6 infection include:

• The use of antiviral medications such as ganciclovir, foscarnet, or cidofovir, which have been shown to inhibit HHV-6 replication 1
• The importance of diagnosing HHV-6 infection using PCR testing of blood, cerebrospinal fluid, or tissue samples, as antibody tests cannot distinguish between active infection and past exposure 1
• The need for monitoring and adverse event management, including the potential for immune reconstitution inflammatory syndrome (IRIS) 1
• The potential for resistance to antiviral medications, which may require switching to a different class of medication 1

In terms of specific treatment regimens, foscarnet (≥180 mg/kg) or ganciclovir (≥10 mg/kg) are recommended for the treatment of HHV-6 encephalitis, with a response rate of 83.8% and 71.4%, respectively 1. It is also important to note that combination therapy with foscarnet and ganciclovir may be effective, but the small sample size limits conclusions regarding its superiority to monotherapy.

Overall, the treatment of HHV-6 infection requires a comprehensive approach that takes into account the patient's underlying condition, the severity of symptoms, and the potential for adverse events. By using antiviral medications such as foscarnet and ganciclovir, and monitoring for potential complications, healthcare providers can improve outcomes and reduce morbidity and mortality associated with HHV-6 infection.

From the Research

HHV-6 Infection

• Human Herpesvirus 6 (HHV-6) is a widespread betaherpesvirus that is genetically related to human cytomegalovirus (HCMV) and encompasses two different species: HHV-6A and HHV-6B 2.
• HHV-6 exhibits a wide cell tropism in vivo and induces a lifelong latent infection in humans, with genomic HHV-6 DNA covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population 2.

Diagnosis and Treatment

• The diagnosis of HHV-6 infection is performed by both serologic and direct methods, with the most prominent technique being the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR 2, 3.
• Antiviral compounds such as 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 2, 4, 3, 5.
• The search for antiviral drugs effective against HHV-6-associated diseases is ongoing, with potential candidates including nucleoside and non-nucleoside analogues, as well as specific protein kinase inhibitors 4.

Clinical Manifestations

• HHV-6 infection can cause a range of clinical manifestations, from asymptomatic to severe diseases, particularly in immunocompromised individuals 2, 3, 5, 6.
• Exanthema subitum, a benign disease of infancy, is associated with primary HHV-6 infection, while reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients 2, 3.
• HHV-6 infection has also been linked to other clinical entities, such as multiple sclerosis, malignancy, infectious mononucleosis, drug hypersensitivity syndromes, and skin eruptions 6.

Immunocompromised Patients

• Immunocompromised patients are at increased risk of severe HHV-6 infections, and early detection of the virus in respiratory samples is critical for timely intervention 5.
• The usefulness of prophylactic or pre-emptive antiviral chemotherapy in immunocompromised patients has not yet been convincingly demonstrated, and controlled studies are needed to evaluate the cost-effectiveness of HHV-6 follow-up and therapy in different clinical situations 3.