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292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials

BACKGROUND: Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reporte...

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Autores principales: Rohde, Maximilian, Carter, Wendy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810561/
http://dx.doi.org/10.1093/ofid/ofz360.367
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author Rohde, Maximilian
Carter, Wendy
author_facet Rohde, Maximilian
Carter, Wendy
author_sort Rohde, Maximilian
collection PubMed
description BACKGROUND: Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reported a possible link between DAA treatment for hepatitis C and reactivation of varicella-zoster virus (VZV). Reported VZV reactivation rates in these studies were 0.23%, 0.72%, 1.50%, 1.74%, and 8.00%. METHODS: To further investigate these reported observations, we analyzed 37 prospective registrational DAA clinical trials, including 13,816 subjects in our analysis. Treatment arms were classified as DAA (N = 7,901), DAA + ribavirin (RBV) (N = 4,348), placebo (N = 997), DAA + IFN (N = 327), or IFN (N = 243). 1,068 (8%) subjects were HIV-coinfected, and 9,024 (65%) subjects were over age 50, both known risk factors for VZV reactivation. Herpes zoster (HZ) events occurring while on-treatment or during follow-up were identified using MedDRA preferred terms. RESULTS: We identified 36 (0.26%) subjects with HZ events. Thirty-two cases occurred during treatment, and 4 during follow-up. One event was considered severe, and the remaining were mild or moderate in severity. Of the 36 total cases reported, 11 (0.14%) were in DAA arms, 21 (0.48%) were in DAA+RBV arms, 4 (0.40%) were in placebo arms, and none were in DAA+IFN or IFN arms (Table 2). For a more direct comparison, we examined a subset of eight trials (N = 3835) containing both a DAA or DAA+RBV arm and a placebo arm. Of the 8 (0.21%) cases reported, 4 (0.14%) were in the DAA/DAA +RBV arms (N = 2838), and 4 (0.40%) were in the placebo arms (N = 997). While rates of VZV reactivation were increased for HIV-coinfected subjects (0.47% vs. 0.24%) and those over age 50 (0.31% vs. 0.17%) (Table 3), they remained similar to or lower than rates reported in previous studies (Table 1). CONCLUSION: Data from prospective DAA clinical trials including 13,816 subjects do not provide evidence for an association between DAAs and VZV reactivation as reported in recent case series and retrospective studies. Low rates of VZV reactivation were observed, particularly in low-risk groups such as those below the age of 50, as would be expected in naturally occurring reactivation. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68105612019-10-28 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials Rohde, Maximilian Carter, Wendy Open Forum Infect Dis Abstracts BACKGROUND: Direct-acting antivirals (DAAs) have substantially increased the rate of sustained virologic response in patients with hepatitis C compared with interferon therapy (IFN), while causing fewer adverse events. However, five recent case series and retrospective studies (Table 1) have reported a possible link between DAA treatment for hepatitis C and reactivation of varicella-zoster virus (VZV). Reported VZV reactivation rates in these studies were 0.23%, 0.72%, 1.50%, 1.74%, and 8.00%. METHODS: To further investigate these reported observations, we analyzed 37 prospective registrational DAA clinical trials, including 13,816 subjects in our analysis. Treatment arms were classified as DAA (N = 7,901), DAA + ribavirin (RBV) (N = 4,348), placebo (N = 997), DAA + IFN (N = 327), or IFN (N = 243). 1,068 (8%) subjects were HIV-coinfected, and 9,024 (65%) subjects were over age 50, both known risk factors for VZV reactivation. Herpes zoster (HZ) events occurring while on-treatment or during follow-up were identified using MedDRA preferred terms. RESULTS: We identified 36 (0.26%) subjects with HZ events. Thirty-two cases occurred during treatment, and 4 during follow-up. One event was considered severe, and the remaining were mild or moderate in severity. Of the 36 total cases reported, 11 (0.14%) were in DAA arms, 21 (0.48%) were in DAA+RBV arms, 4 (0.40%) were in placebo arms, and none were in DAA+IFN or IFN arms (Table 2). For a more direct comparison, we examined a subset of eight trials (N = 3835) containing both a DAA or DAA+RBV arm and a placebo arm. Of the 8 (0.21%) cases reported, 4 (0.14%) were in the DAA/DAA +RBV arms (N = 2838), and 4 (0.40%) were in the placebo arms (N = 997). While rates of VZV reactivation were increased for HIV-coinfected subjects (0.47% vs. 0.24%) and those over age 50 (0.31% vs. 0.17%) (Table 3), they remained similar to or lower than rates reported in previous studies (Table 1). CONCLUSION: Data from prospective DAA clinical trials including 13,816 subjects do not provide evidence for an association between DAAs and VZV reactivation as reported in recent case series and retrospective studies. Low rates of VZV reactivation were observed, particularly in low-risk groups such as those below the age of 50, as would be expected in naturally occurring reactivation. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6810561/ http://dx.doi.org/10.1093/ofid/ofz360.367 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Rohde, Maximilian
Carter, Wendy
292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title_full 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title_fullStr 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title_full_unstemmed 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title_short 292. No association Between Direct-acting Antiviral (DAA) Therapy and Varicella-Zoster Virus (VSV) Reactivation in an Analysis of 37 Prospective Clinical Trials
title_sort 292. no association between direct-acting antiviral (daa) therapy and varicella-zoster virus (vsv) reactivation in an analysis of 37 prospective clinical trials
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810561/
http://dx.doi.org/10.1093/ofid/ofz360.367
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