Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis
Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases - (2023) vom: 31. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kampouri, Eleftheria [VerfasserIn] |
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| Links: |
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| Themen: |
Allogeneic haematopoietic cell transplantation |
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| Anmerkungen: |
Date Revised 02.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.cmi.2023.07.026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360318746 |
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| 100 | 1 | |a Kampouri, Eleftheria |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis |
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| 500 | |a Date Revised 02.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Allogeneic haematopoietic cell transplantation | |
| 650 | 4 | |a CMV prophylaxis | |
| 650 | 4 | |a HHV-6 | |
| 650 | 4 | |a Letermovir | |
| 650 | 4 | |a Post-transplantation cyclophosphamide | |
| 700 | 1 | |a Zamora, Danniel |e verfasserin |4 aut | |
| 700 | 1 | |a Kiem, Erika S |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Winnie |e verfasserin |4 aut | |
| 700 | 1 | |a Ibrahimi, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Blazevic, Rachel L |e verfasserin |4 aut | |
| 700 | 1 | |a Lovas, Erika A |e verfasserin |4 aut | |
| 700 | 1 | |a Kimball, Louise E |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Meei-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Jerome, Keith R |e verfasserin |4 aut | |
| 700 | 1 | |a Ueda Oshima, Masumi |e verfasserin |4 aut | |
| 700 | 1 | |a Mielcarek, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Zerr, Danielle M |e verfasserin |4 aut | |
| 700 | 1 | |a Boeckh, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Krantz, Elizabeth M |e verfasserin |4 aut | |
| 700 | 1 | |a Hill, Joshua A |e verfasserin |4 aut | |
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