Evidence before this study
nirmatrelvir, molnupiravir and nirmatrelvir
Molnupiravir and ritonavir-boosted nirmatrelvir are the two leading oral antiviral drugs for patients with COVID-19. We searched PubMed for studies published in English from Jan 1, 2020, to July 11, 2023, using the terms: “randomised” AND [“nirmatrelvir OR paxlovid”] AND “molnupiravir”. Both molnupiravir and nirmatrelvir have shown in-vivo antiviral activity and clinical benefit, but there have been no direct randomised head-to-head comparisons. A network metaanalysis suggested that nirmatrelvir is slightly more effective than molnupiravir. Comparisons between the preregistration studies are confounded by substantial differences in the study populations, and timing of the studies. Associations between the use of these drugs and the risk of viral mutations (molnupiravir) and viral rebound (nirmatrelvir) have both been reported, although their incidence and impact are uncertain.