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. 2023 Nov;29(11):1450.e1-1450.e7.
doi: 10.1016/j.cmi.2023.07.026. Epub 2023 Jul 31.

Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis

Eleftheria Kampouri  1 , Danniel Zamora  2 , Erika S Kiem  1 , Winnie Liu  1 , Sarah Ibrahimi  1 , Rachel L Blazevic  1 , Erika A Lovas  1 , Louise E Kimball  1 , Meei-Li Huang  3 , Keith R Jerome  4 , Masumi Ueda Oshima  5 , Marco Mielcarek  5 , Danielle M Zerr  6 , Michael J Boeckh  7 , Elizabeth M Krantz  1 , Joshua A Hill  8
Affiliations

Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis

Eleftheria Kampouri et al. Clin Microbiol Infect. 2023 Nov.

Abstract

Objectives: Letermovir for cytomegalovirus (CMV) prophylaxis in allogeneic haematopoietic cell transplant (HCT) recipients has decreased anti-CMV therapy use. Contrary to letermovir, anti-CMV antivirals are also active against human herpesvirus-6 (HHV-6). We assessed changes in HHV-6 epidemiology in the post-letermovir era.

Methods: We conducted a retrospective cohort study of CMV-seropositive allogeneic HCT recipients comparing time periods before and after routine use of prophylactic letermovir. HHV-6 testing was at the discretion of clinicians. We computed the cumulative incidence of broad-spectrum antiviral initiation (foscarnet, (val)ganciclovir, and/or cidofovir), HHV-6 testing, and HHV-6 detection in blood and cerebrospinal fluid within 100 days after HCT. We used Cox proportional-hazards models with stabilized inverse probability of treatment weights to compare outcomes between cohorts balanced for baseline factors.

Results: We analysed 738 patients, 376 in the pre-letermovir and 362 in the post-letermovir cohort. Broad-spectrum antiviral initiation incidence decreased from 65% (95% CI, 60-70%) pre-letermovir to 21% (95% CI, 17-25%) post-letermovir. The cumulative incidence of HHV-6 testing (17% [95% CI, 13-21%] pre-letermovir versus 13% [95% CI, 10-16%] post-letermovir), detection (3% [95% CI, 1-5%] in both cohorts), and HHV-6 encephalitis (0.5% [95% CI, 0.1-1.8%] pre-letermovir and 0.6% [95% CI, 0.1-1.9%] post-letermovir) were similar between cohorts. First HHV-6 detection occurred at a median of 37 days (interquartile range, 18-58) in the pre-letermovir cohort and 27 (interquartile range, 25-34) in the post-letermovir cohort. In a weighted model, there was no association between the pre-versus post-letermovir cohort and HHV-6 detection (adjusted hazard ratio, 1.08; 95% CI, 0.44-2.62).

Discussion: Despite a large decrease in broad-spectrum antivirals after the introduction of letermovir prophylaxis in CMV-seropositive allogeneic HCT recipients, there was no evidence for increased clinically detected HHV-6 reactivation and disease.

Keywords: Allogeneic haematopoietic cell transplantation; CMV prophylaxis; HHV-6; Letermovir; Post-transplantation cyclophosphamide.

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Conflict of interest statement

Transparency declaration

Potential conflicts of interest:

D.M.Z. has served as a consultant for a clinical endpoint adjudication committee for AlloVir and has received research support from Merck.

M.J.B. has served as a consultant for Symbio, AlloVir, and Merck and has received research support from Merck.

J.A.H. has served as a consultant for Symbio, Gilead, and AlloVir and has received research support from Merck and AlloVir.

Figures

Figure 1:
Figure 1:. Antiviral use by week
A: Percentage of patients in the post-LTV cohort receiving letermovir per week after HCT. B: Percentage of patients receiving broad-spectrum antiviral therapy per week after HCT, stratified by cohort.
Figure 2:
Figure 2:. Cumulative incidence plot of time to broad-spectrum antiviral therapy initiation.
Cumulative incidence curves of time to broad-spectrum antiviral therapy initiation within 100 days from HCT, treating death and subsequent HCT as competing risks and stratified by cohort. Cumulative incidence rates with 95% confidence intervals (CI) within 100 days from HCT: 65% (95% CI: 60–70%) in the pre-LTV cohort and 21% (95% CI: 17–25%) in the post-LTV cohort.
Figure 3:
Figure 3:. Cumulative incidence plots of time to HHV-6 testing and detection
A: Cumulative incidence curves of time to HHV-6 testing within 100 days from HCT, treating death and subsequent HCT as competing risks and stratified by cohort. Cumulative incidence rates with 95% confidence intervals (CI) within 100 days from HCT: 17% (95% CI: 13–21%) in the pre-LTV cohort and 13% (95% CI: 10–16%) in the post-LTV cohort. B: Cumulative incidence curves of time to HHV-6 detection within 100 days from HCT, treating death and subsequent HCT as competing risks and stratified by cohort. Cumulative incidence rates with 95% confidence intervals (CI) within 100 days from HCT: 3% (95% CI: 1–5%) in both cohorts.
See this image and copyright information in PMC

References

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