CHEST INFECTIONS: ORIGINAL RESEARCH| VOLUME 164, ISSUE 3, P625-636, SEPTEMBER 2023

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, et al

Chest 2023; 164: 625-636 Open Access Published:March 31, 2023

DOI:https://doi.org/10.1016/j.chest.2023.03.040

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