Added value of this study
death
MUTANT
For COVID-19, comparison of antiviral drugs using clinical endpoints such as hospitalisation or death now requires prohibitively large sample sizes because these outcomes have become increasingly rare. By contrast, the pharmacometric approach described here provides a quantitative measure of antiviral effects in patients with tractable sample sizes. To our knowledge, this randomised study provides the first direct comparison of the in-vivo antiviral effects of molnupiravir and ritonavir-boosted nirmatrelvir. It shows that both drugs accelerate SARS-CoV-2 viral clearance but that ritonavir-boosted nirmatrelvir results in faster clearance than molnupiravir; that viral rebound occurs relatively often in a healthy population following ritonavir-boosted nirmatrelvir; and that mutant viruses are generated frequently following molnupiravir treatment.