Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA.
Blood. 2020 Apr 23;135(17):1447-1451. doi: 10.1182/blood.2019004315.
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.
人类疱疹病毒 6B(HHV-6B)在异基因造血细胞移植(HCT)后经常重新激活。目前尚无预防 HHV-6B 再激活的抗病毒治疗的随机研究。布立昔洛韦对 HHV-6B 和其他 DNA 病毒具有高体外活性,但尚未证明其对 HHV-6B 的体内活性。我们对异基因 HCT 后每周两次口服布立昔洛韦预防巨细胞病毒的随机对照试验进行了事后分析,以研究布立昔洛韦对 HHV-6B 再激活的影响。我们纳入了在 HCT 后 2 周内随机分组且在随机分组后至少接受 6 剂连续研究药物的患者。我们在 HCT 后第 6 周检测了患者的血浆 HHV-6B。该队列包括 92 名接受布立昔洛韦治疗和 61 名接受安慰剂治疗的患者。接受布立昔洛韦治疗的患者在 HCT 后第 42 天的 HHV-6B 血浆检测累积发生率明显低于接受安慰剂治疗的患者(14.2%比 32.4%;对数秩检验,0.019)。在调整后的 Cox 模型中,布立昔洛韦暴露与 HHV-6B 血浆检测的风险降低相关(风险比,0.40;95%置信区间,0.20-0.80)。总之,在一项随机对照试验的事后分析中,布立昔洛韦预防可降低异基因 HCT 后 HHV-6B 的再激活。这些数据支持研究静脉用布立昔洛韦预防 HHV-6B。