Human herpesvirus 6 in transplant recipients: an update on diagnostic and treatment strategies

Abstract

Purpose of review: The current review article focuses on recent advances in the approach to the diagnosis and treatment of human herpesvirus 6B (HHV-6B) in hematopoietic cell and solid organ transplant recipients.

Recent findings: Over the past few years, key studies have broadened our understanding of best practices for the prevention and treatment of HHV-6B encephalitis after transplantation. Moreover, important data have been reported that support a potential role of HHV-6B reactivation in the development of acute graft-versus-host disease and lower respiratory tract disease in transplant recipients. Finally, increasing recognition of inherited chromosomally integrated HHV-6 (iciHHV-6) and an expanding array of diagnostic tools have increased our understanding of the potential for complications related to viral reactivation originating from iciHHV-6 in donors or recipients.

Summary: Recent advances in diagnostic tools, disease associations, and potential treatments for HHV-6B present abundant opportunities for improving our understanding and management of this complex virus in transplant recipients.

Figure 1.. Evaluation for, and management of, suspected HHV-6 disease after hematopoietic cell or solid organ transplantation.

qPCR indicates quantitative PCR; CSF, cerebrospinal fluid; ID, infectious diseases. ^AHHV-6B DNA is typically detected in blood by PCR in patients with HHV-6B encephalitis. If the plasma or CSF HHV-6B viral load does not decrease >1 log₁₀ copies/ml after ≥2 weeks of therapy or is persistently positive for ≥3 consecutive weeks, test for iciHHV-6. ^BAny detection of HHV-6 species A or B DNA in CSF is considered abnormal. However, HHV-6 DNA can be detected in the CSF in the absence of clinical symptoms[17] or when the pre-test probability for HHV-6B encephalitis is low.[18] Close monitoring without treatment can be considered in select cases with the guidance of an ID consult. These recommendations are based on expert opinion and adapted from the 7th European Conference on Infections in Leukaemia (ECIL) 2017 guidelines.[58]

Figure 2.. In vitro activity of currently available and investigational antiviral agents for HHV-6B.

ACV indicates acyclovir; GCV, ganciclovir; PFA, foscarnet; CDV, cidofovir; LMV, letermovir; ART, artesunate; BCV, brincidofovir; MBV, maribavir; CPV, cyclopropavir. This figure shows the range of in vitro activity reported for antiviral compounds that are currently available or in development. The data represent the half-maximal effective concentration (EC₅₀) of the compounds in vitro, or the concentration at which inhibition of viral growth is 50% of the maximum response within the specified exposure time. For the purposes of categorizing the in vitro activity data, an EC₅₀ value of 10 μM was selected as a threshold for determining the relative strength. A variety of methods were used in different studies to generate these data; data generated by a plaque reduction assay, which is generally considered the gold standard, are in solid circles. These data are adapted from Chemaly et al, Antiviral Res. 2019 Mar;163:50–58.^{44 A}The reported EC₅₀ values for LMV and ART are from studies using HHV-6A; data for HHV-6B are unavailable. ^BNot clinically available. ^CValues shown represent the minimum detected value (primary data reported as >20 μM and >106 μM).