(ASPOT45) Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease

Background: Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD).

Objectives: To examine the 14-day risk of serious adverse events in older adults with CKD newly prescribed an antiviral at varied doses.

Methods: We conducted a retrospective population-based cohort study in Ontario, Canada (2008-2022) using linked healthcare data. Individuals in Ontario, Canada (2008-2022) aged ≥66 years, with an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2, and who were new users of an antiviral. We compared individuals who initiated a higher-dose antiviral (acyclovir, 1,600-4,000 mg/d or valacyclovir, 3,000-4,000 mg/d or famciclovir, 1,500 mg/d) vs. lower-dose antiviral (acyclovir, 400- < 1,600 mg/day; valacyclovir, 500- < 3,000 mg/day; famciclovir, 125- < 1,500 mg/day). The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI using lab values was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health in the primary and secondary cohorts. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression in both cohorts.

Results: In the primary cohort, higher- versus lower-dose antiviral treatment was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI (weighted number of events, 307 of 24,667 [1.24%] versus 239 of 24,662 [0.97%], respectively; weighted RR, 1.29 [95% CI, 0.95 to 1.75]; weighted RD, 0.28% [95% CI, -0.03% to 0.59%]). However, higher- versus lower-dose antiviral treatment was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8,407 [0.83%] versus 18 of 8,230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87 to 7.87]; weighted RD, 0.62% [95% CI, 0.37% to 0.86%]).

Conclusions: In older adults with CKD, starting an antiviral at a higher vs lower dose was associated with a higher risk of AKI, although the absolute risk of this event was < 1%.