1. Human Herpesvirus 6B and Lower Respiratory Tract Disease After Hematopoietic Cell Transplantation.
- Author
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Hill JA, Vande Vusse LK, Xie H, Chung EL, Yeung CCS, Seo S, Stevens-Ayers T, Fisher CE, Huang ML, Stewart FM, Jerome KR, Zerr DM, Corey L, Leisenring WM, and Boeckh M
- Subjects
- Adult, Antiviral Agents therapeutic use, Bronchoalveolar Lavage Fluid virology, Cohort Studies, DNA, Viral analysis, Female, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation mortality, Herpesvirus 6, Human genetics, Humans, Male, Middle Aged, RNA, Viral analysis, Respiratory Tract Infections drug therapy, Respiratory Tract Infections mortality, Retrospective Studies, Roseolovirus Infections drug therapy, Roseolovirus Infections mortality, Viral Load, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Herpesvirus 6, Human isolation & purification, Respiratory Tract Infections virology, Roseolovirus Infections virology
- Abstract
Purpose: Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear., Methods: We tested BALF for HHV-6B DNA using polymerase chain reaction in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992 to 2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B
+ BALF with overall mortality, death from respiratory failure, and the effect of anti-HHV-6B antivirals on these outcomes. We used branched-chain RNA in situ hybridization to detect HHV-6 messenger RNA ( U41 and U57 transcripts) in lung tissue., Results: We detected HHV-6B+ BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B+ BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.41-3.39) and death from respiratory failure (aHR, 2.50; 95% CI, 1.56-4.01) compared with subjects with HHV-6B- BALF. Subjects with HHV-6B+ BALF who received antivirals within 3 days pre-BAL had an approximately 1 log10 lower median HHV-6B BALF viral load, as well as a lower risk of overall mortality (aHR, 0.42; 95% CI, 0.16-1.10), compared with subjects with HHV-6B+ BALF not receiving antivirals. We detected intraparenchymal HHV-6 gene expression by RNA in situ hybridization in lung tissue in all three tested subjects with HHV-6B+ BALF and sufficient tissue RNA preservation., Conclusion: These data provide evidence that HHV-6B detection in BALF is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with LRTD. Definitive evidence of causation will require a randomized prevention or treatment trial.- Published
- 2019
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