Valaciclovir for Epstein-Barr virus suppression in moderate-to-severe COPD: a randomized, double-blind, placebo-controlled trial

Dermot A. Linden*, Hong Guo-Parke, Michael C. McKelvey, Gisli G. Einarsson, Andrew J. Lee, Derek J. Fairley, Vanessa Brown, Gavin Lundy, Christina Campbell, Danielle Logan, Margaret McFarland, Dave Singh, Daniel F. McAuley, Clifford C. Taggart, Joseph C. Kidney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Abstract

Background
Epstein-Barr virus (EBV) frequently is measured at high levels in COPD using sputum quantitative polymerase chain reaction, whereas airway immunohistochemistry analysis has shown EBV detection to be common in severe disease.

Research Question
Is valaciclovir safe and effective for EBV suppression in COPD?

Study Design and Methods
The Epstein-Barr Virus Suppression in COPD (EViSCO) trial was a randomized double-blind placebo-controlled trial conducted at the Mater Hospital Belfast, Northern Ireland. Eligible patients had stable moderate-to-severe COPD and sputum EBV (measured using quantitative polymerase chain reaction) and were assigned randomly (1:1) to valaciclovir (1 g tid) or matching placebo for 8 weeks. The primary efficacy outcome was sputum EBV suppression (defined as ≥ 90% sputum viral load reduction) at week 8. The primary safety outcome was the incidence of serious adverse reactions. Secondary outcome measures were FEV1 and drug tolerability. Exploratory outcomes included changes in quality of life, sputum cell counts, and cytokines.

Results
From November 2, 2018, through March 12, 2020, 84 patients were assigned randomly (n = 43 to valaciclovir). Eighty-one patients completed trial follow-up and were included in the intention-to-treat analysis of the primary outcome. A greater number of participants in the valaciclovir group achieved EBV suppression (n = 36 [87.8%] vs n = 17 [42.5%]; P < .001). Valaciclovir was associated with a significant reduction in sputum EBV titer compared with placebo (–90,404 copies/mL [interquartile range, –298,000 to –15,200 copies/mL] vs –3,940 copies/mL [interquartile range, –114,400 to 50,150 copies/mL]; P = .002). A statistically nonsignificant 24-mL numerical FEV1 increase was shown in the valaciclovir group (difference, –44 mL [95% CI, –150 to 62 mL]; P = .41). However, a reduction in sputum white cell count was noted in the valaciclovir group compared with the placebo group (difference, 2.89 [95% CI, 1.5 × 106-7.4 × 106]; P = .003).

Interpretation
Valaciclovir is safe and effective for EBV suppression in COPD and may attenuate the sputum inflammatory cell infiltrate. The findings from the current study provide support for a larger trial to evaluate long-term clinical outcomes.

Trial Registry
ClinicalTrials.gov; No.: NCT03699904; URL: www.clinicaltrials.gov


Original languageEnglish
Pages (from-to)625-636
Number of pages12
JournalChest
Volume164
Issue number3
Early online date31 Mar 2023
DOIs
Publication statusPublished - Sept 2023

Keywords

  • COPD
  • Epstein-Barr virus
  • placebo-controlled trial
  • randomized control trial
  • valaciclovir

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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