Valaciclovir for Epstein-Barr virus suppression in Chronic Obstructive Pulmonary Disease: A Randomised Controlled Trial (EViSCO)

<b>Background:</b> Epstein-Barr virus (EBV) is frequently detected at high levels in stable COPD using sputum quantitative polymerase chain reaction (qPCR) whilst airway immunohistochemistry indicates EBV is more common in severe disease. <b>Objectives:</b> To evaluate the safety and efficacy of valaciclovir for EBV suppression in COPD. <b>Methods:</b> EViSCO was a randomised, double-blind, placebo-controlled trial. Eligible participants with moderate-to-severe COPD and sputum EBV detection using qPCR were randomised to&nbsp;valaciclovir 1000mg or matching placebo thrice daily for 8 weeks. The primary efficacy outcome was EBV suppression (defined as &gt;90% sputum viral load reduction) at week 8. The primary safety outcome was the incidence of serious adverse reactions (SARs).&nbsp;Secondary outcomes were FEV₁ and drug compliance. Exploratory outcomes included quality-of-life, sputum biomarkers and microbiota. <b>Results:</b> In total, 84 patients were randomly assigned to valaciclovir or placebo with 81 included in the intention-to-treat analysis (41 valaciclovir). A greater number of participants in the valaciclovir group achieved EBV suppression (n=36 (87.8%) vs. n=17 (42.5%);&nbsp;<i>P</i>&nbsp;&lt;0.001).&nbsp;Valaciclovir was associated with a significant reduction in sputum EBV qPCR titre at week 8 (-90404 copies/ml [IQR -298000, -15200] vs. -3940 copies/ml&nbsp;[IQR -114400, 50150];&nbsp;<i>P</i>=0.002). There were no SARs in either group. We found no between-group differences in FEV₁&nbsp;or&nbsp;quality-of-life. Sputum total cell count was reduced in the valaciclovir group (difference 2.89;[95% CI 1.5 x10⁶-7.4 x 10⁶];&nbsp;<i>P</i>=0.003). <b>Conclusions:</b> Valaciclovir is safe and effective for EBV suppression in COPD and may attenuate inflammation.