This post hoc exploratory analysis of the ZEDS multicenter, double-masked, placebo-controlled RCT evaluated whether the protective effects of 12 months of daily valacyclovir 1000 mg vs. placebo varied over time in 527 immunocompetent adults with herpes zoster ophthalmicus (HZO) and active keratitis or iritis, followed for 18 months total.
Time-varying Cox analyses showed valacyclovir had lower hazard vs. placebo during the 0–6 month window (HR 0.71; 95% CI 0.49–1.01) and the 12–18 month observation window (HR 0.57; 95% CI 0.27–1.18), but near-null benefit from 6–12 months (HR 0.99; 95% CI 0.52–1.86); no interval reached statistical significance.
- Post hoc exploratory analysis; findings are hypothesis-generating, not confirmatory. - All time-varying comparisons were underpowered and did not reach statistical significance. - Subgroup analyses across time windows further reduce event counts, widening confidence intervals.
Protective effects of valacyclovir appear concentrated in the first 6 months of treatment and may persist briefly after stopping, supporting the current recommendation to complete a full 1-year course in HZO patients with active keratitis or iritis. Clinicians should not interpret the mid-treatment attenuation (6–12 months) as a signal to stop therapy early.
