Nirmatrelvir treatment duration and frequency of COVID-19 rebound

Nirmatrelvir has been shown to reduce morbidity and mortality associated with COVID-19. However, it is underutilized due to concerns regarding COVID-19 symptom rebound following nirmatrelvir's standard 5-day course. This study aims to identify and evaluate a nirmatrelvir dosage regimen that lowers symptom rebound.

Based on nirmatrelvir pharmacokinetics, we propose a novel 8-day regimen: two doses twice-daily followed by six doses once-daily to reduce rebound frequency. We then carried out a retrospective case series study of clinical outcomes among our patients to investigate their frequency of COVID-19 symptom rebound following nirmatrelvir usage.

Among the 58 prescribed case patients, 49 filled and initiated the prescription. Of those 49 patients, four took the medication for fewer than 5 days, 24 for 5 days (standard regimen), and 21 for 7 or 8 days (extended regimen). Among 5-day treatment cases (n = 24), 8 (33%) experienced clinical rebound, whereas among the 7-day or 8-day treatment cases (n = 21), 2 (9.5%) experienced rebound.

These findings suggest that a longer nirmatrelvir/ritonavir course might reduce rebound symptoms compared to the standard 5-day regimen.