VALZ‐Pilot: High‐dose valacyclovir treatment in patients with early‐stage Alzheimer's disease

Introduction Herpes simplex virus (HSV) may be involved in Alzheimer's disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication. Methods This phase‐II pilot trial involved valacyclovir administration (thrice daily, 500 mg week 1, 1000 mg weeks 2–4) to persons aged ≥ 65 years with early‐stage AD, anti‐HSV immunoglobulin G, and apolipoprotein E ε4. Intervention safety, tolerability, feasibility, and effects on Mini‐Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarkers were evaluated. Results Thirty‐two of 33 subjects completed the trial on full dosage. Eighteen percent experienced likely intervention‐related mild, temporary adverse events. CSF acyclovir concentrations were mean 5.29 ± 2.31 μmol/L. CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 concentrations increased (P = .02 and .03). Discussion Four weeks of high‐dose valacyclovir treatment was safe, tolerable, and feasible in early‐stage AD. Our findings may guide future trial design.