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

Blood. 2020 Apr 23;135(17):1447-1451. doi: 10.1182/blood.2019004315.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Cohort Studies
  • Cytosine / administration & dosage
  • Cytosine / analogs & derivatives*
  • DNA, Viral
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / isolation & purification*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage*
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Roseolovirus Infections / drug therapy*
  • Roseolovirus Infections / epidemiology
  • Roseolovirus Infections / etiology
  • United States / epidemiology
  • Viral Load
  • Viremia / drug therapy*
  • Viremia / epidemiology
  • Viremia / etiology
  • Virus Activation
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • brincidofovir
  • Cytosine