OO021a - VALZ-PILOT: HIGH-DOSE VALACYCLOVIR TREATMENT IN PATIENTS WITH EARLY-STAGE ALZHEIMER'S DISEASE (ID 867)
Abstract
Aims
Herpes simplex virus (HSV) may be involved in Alzheimer’s disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication. Our aim was to evaluate safety, tolerability, feasibility, clinical efficacy, and effects on cerebrospinal fluid (CSF) biomarkers with high-dose valacyclovir administration to patients with early-stage AD.
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, 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 (mean 5.29 ± 2.31 µmol/L) were in the therapeutic range. CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentrations increased (p = 0.02 and 0.03).
Conclusions
Valacyclovir treatment was safe, tolerable, and feasible for patients with early-stage AD, HSV, and APOE ε4. These findings may guide the design of RCTs for the assessment of antiviral treatment effectiveness for such patients in terms of AD symptoms, progression, and pathology.
