Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT

Abstract

Human herpesvirus 6B (HHV-6B) frequently reactivates after allogeneic hematopoietic cell transplantation (HCT). There are no randomized studies of antiviral treatments to prevent HHV-6B reactivation. Brincidofovir has high in vitro activity against HHV-6B and other DNA viruses, but its in vivo activity for HHV-6B has not been demonstrated. We performed a post hoc analysis of a randomized controlled trial of twice-weekly oral brincidofovir for cytomegalovirus prophylaxis after allogeneic HCT to study the effect of brincidofovir on HHV-6B reactivation. We included patients randomized within 2 weeks of HCT and who received at least 6 consecutive doses of study drug after randomization. We tested plasma for HHV-6B through week 6 post-HCT. The cohort consisted of 92 patients receiving brincidofovir and 61 receiving placebo. The cumulative incidence of HHV-6B plasma detection through day 42 post-HCT was significantly lower among patients receiving brincidofovir (14.2%) compared with placebo (32.4%; log-rank, 0.019). In an adjusted Cox model, brincidofovir exposure remained associated with a lower hazard for HHV-6B plasma detection (hazard ratio, 0.40; 95% confidence interval, 0.20-0.80). In conclusion, brincidofovir prophylaxis reduced HHV-6B reactivation after allogeneic HCT in a post hoc analysis of a randomized controlled trial. These data support the study of intravenous brincidofovir for HHV-6B prophylaxis.

Investigation of Inherited Chromosomally Integrated Human Herpesvirus-6A+ and -6B+ in a Patient with Ulipristal Acetate-Induced Fulminant Hepatic Failure

“…In immunosuppressed patients, reactivated HHV-6 from iciHHV-6 can induce acute liver failure and acute rejection, as demonstrated in a 5-year transplant recipient, by the presence of mRNA and late viral protein in the sole iciHHV-6B+ liver allograft [31]. Reactivated HHV-6 from iciHHV-6 is susceptible to antiviral drugs and can be treated with ganciclovir, valganciclovir, cidofovir, brincidofovir, or foscarnet [28,[31][32][33][34]. However, antiviral treatment, considered a therapeutic option for iciHHV-6-associated diseases, leads to variable clinical improvement [24,33,35,36].…”

Human Herpes Virus-6 (HHV-6) Reactivation after Hematopoietic Cell Transplant and Chimeric Antigen Receptor (CAR)- T Cell Therapy: A Shifting Landscape

“…Letermovir lacks activity against HHV-6B, and its use has led to a substantial decrease in the use of broad-spectrum antivirals for CMV [ 28 , 29 , 30 ]. Since these broad-spectrum antivirals have a prophylactic effect against HHV-6B, an increase in HHV-6B reactivation could be possible [ 21 , 31 , 32 , 33 ]. A large retrospective study among 738 HCT recipients compared the incidence of HHV-6B reactivation and disease (by clinical testing) in two cohorts: before and after the routine use of letermovir [ 34 ].…”

Adenovirus infection in allogeneic hematopoietic cell transplantation

“…Studies are ongoing to repurpose the drug for other infections such as HHV-6, monkeypox, and smallpox. [57][58][59] Another drug active against AdV is ribavirin, a guanosine nucleoside analogue, that has in vitro activity against DNA and RNA viruses by inhibiting viral polymerases, viral RNA capping, and increasing the mutation rate in newly synthesized DNA. Importantly, in vitro analysis showed that ribavirin is effective only against AdV type C while in vivo efficacy is debated.…”

“…Unfortunately, subsequent phases of drug development as prophylaxis for CMV and preventive therapy for AdV failed to achieve the primary endpoints 56 so the drug is no longer available, even for compassionate use. Studies are ongoing to repurpose the drug for other infections such as HHV‐6, monkeypox, and smallpox 57–59 …”