A new study from the Medical University of Warsaw suggests that HHV-6 and HHV-7 are important co-factors for the development of CMV infection post-transplant in allogeneic hematopoietic stem cell transplantation patients. Additionally, the presence of HHV-7 and CMV together may result in more severe infections than either virus alone.
In past studies, both HHV-6 and HHV-7 have been shown to have potential roles in fostering the reactivation of CMV (HHV-6 has been associated with CMV co-reactivation after stem cell transplantation [Aoki 2015, Quintela 2016], and HHV-7 co-infections with CMV have previously been associated with higher CMV viral load as well as longer duration of HHV-7 infection in HSCT patients [Tomaszewska 2014, Chapenko 2012]).
In this study, serum samples were taken weekly from 142 alloHSCT patients for up to 104 days post-transplant with a median of 14 samples total per patient. The presence of CMV, HHV-6, and HHV-7 was tested for by qPCR in order to determine viral load and duration of viremia for each of the three betaherpesviruses. Patients were treated prophylactically with acyclovir, but this treatment did not significantly affect viral reactivation.
Initial testing showed that 113 of the 142 patients (79.6%) were positive for one or more of the viruses, and of those with co-infections, HHV-6 and HHV-7 tended to precede CMV reactivation. In co-infections of CMV and HHV-6 or CMV and HHV-7, there was a marked difference in onset of viremia between the two viruses present. In these groups, HHV-6 infection was detected at a median of 22 days while the corresponding CMV infection was detected at 30 days, and HHV-7 infection was also detected at a median of 22 days while its corresponding CMV infection began at a median of 38 days. In contrast, co-infections of HHV-6 and HHV-7 did not significantly differ in onset of viremia, as both viruses were detected at a median of 21 days in this group.
Additionally, HHV-7/CMV co-infections resulted in longer durations of viremia for each of the viruses. CMV lasted for a median of 37 days when associated with HHV-7 as opposed to 11.5 days when it was the only virus present. Similarly, HHV-7 viremia lasted a median of 30 days when associated with CMV in contrast to 11 days when presenting alone. This synergistic relationship was absent in cases of HHV-6/HHV-7 co-infection.
Viral load followed a similar trend, with significantly higher levels of both CMV and HHV-7 in CMV/HHV-7 co-infections compared to single infections by either virus. A longer duration of CMV viremia and a higher viral load was also associated with transplants from matched unrelated donors as opposed to related donors.
Read the full paper here.