Valaciclovir safe, efficacious for Epstein-Barr virus suppression in COPD

Key takeaways:

• More than 85% of patients with COPD receiving valaciclovir for 8 weeks suppressed the Epstein-Barr virus.
• No patients reported any serious adverse reactions to the treatment.

Among patients with COPD and sputum Epstein-Barr virus, valaciclovir three times a day for 8 weeks helped more individuals suppress the virus than placebo, according to study results published in CHEST.

“Notably, Epstein-Barr virus (EBV) suppression with valaciclovir has been shown to improve clinical outcomes in infectious mononucleosis,” Dermot A. Linden, PhD, clinical research fellow at the Queen’s University Belfast, and colleagues wrote. “Furthermore, Walling et al found that valaciclovir 1 g [three times a day] for 8 weeks inhibited EBV replication with clinical resolution of oral hairy leukoplakia.”

In a randomized, single center, double-blind, placebo-controlled trial, Linden and colleagues assessed 84 patients with stable moderate to severe COPD and sputum EBV to see how valaciclovir performs against placebo when evaluating sputum EBV suppression (≥ 90% sputum viral load reduction) after 8 weeks of treatment.

Researchers also compared lung function, serious adverse reactions and drug tolerability between the two treatment groups.

Of the total cohort, 43 patients (mean age, 63.1 years; 67.4% men) received 1 g valaciclovir three times a day for 8 weeks, whereas the remaining 41 patients (mean age, 60.3 years; 63.4% men) received matching placebo. Researchers noted that three patients (valaciclovir, n = 2; placebo, n = 1) were lost to follow-up and not included in the analysis.

Among those receiving valaciclovir, 87.8% (n = 36) met the criteria for EBV suppression, whereas fewer patients receiving placebo met this endpoint (42.5%; n = 17; P < .001).

Following in accordance with the above finding, researchers found greater declines in sputum EBV titer in the valaciclovir group vs. the placebo group (–90,404 copies/mL vs. –3,940 copies/mL; P = .002) when assessed at week 8.

At baseline, mean lung function was comparable between the valaciclovir group and the placebo group (57.3 percent-predicted FEV₁ vs. 56.7 percent-predicted FEV₁), and this outcome did not significantly differ between the two groups with these measures at week 8 (valaciclovir, n = 36; placebo, n = 34).

Researchers further found that the difference in drug compliance was nonsignificant.

Quality of life, measured via the COPD Assessment Test and the EQ-5D-5L questionnaire utility index, was also not significantly different when comparing the two groups, according to researchers.

In addition to the outcomes already highlighted, researchers evaluated sputum total cell counts of both groups and found that patients receiving valaciclovir had a lower count at week 8 vs. patients receiving placebo (P = .003).

When evaluating drug safety, researchers looked at outcomes within the total cohort plus the cohort of those lost to follow up in this study.

Notably, none of the patients reported any serious adverse reactions to their assigned treatment, and a similar proportion of patients from each group experienced treatment-emergent adverse events (valaciclovir, n = 26 vs. placebo, n = 31).

“The positive primary end point findings regarding EBV suppression, coupled with the observed treatment effect on sputum total cell counts, provide support to perform a longer and larger multicenter study focused on the impact of EBV suppression on clinical outcomes in COPD,” Linden and colleagues wrote.

Findings from this study by Linden and colleagues may suggest that EBV is associated with morbidity of COPD in addition to its known links to cancers and autoimmune conditions, Henry H. Balfour Jr., MD, of the departments of laboratory medicine and pathology and pediatrics at the University of Minnesota Medical School, wrote an accompanying editorial.

In addition to a longer study duration, Balfour suggested that future research look into the antiviral medicine, tenofovir, in this patient population.

“The tenofovir prodrugs, tenofovir disoproxil fumarate and tenofovir alafenamide, have good activity against EBV in vitro, and they might be worth investigating if a subsequent trial in COPD patients is performed,” Balfour wrote.

References:

• Balfour HH. CHEST. 2023;doi:10.1016/j.chest.2023.04.012.
• Walling DM, et al. J Infect Dis. 2003;doi:10.1086/378072.