Nirmatrelvir plus ritonavir for ambulatory COVID-19: Expanding evidence, expanding role

The prevention and treatment algorithm for COVID-19 begins with vaccination. Although vaccines have proved exceptional, the need for effective therapeutics for SARS-CoV-2 infection remains: Vaccine and booster uptake is heterogeneous, infection can occur in vaccinated persons, protection can wane with time, additional immune-evasive subvariants continue to emerge, some people are at higher risk for severe disease, and immunocompromised persons may mount a suboptimal protective response even if they are vaccinated or have previously been infected. Based on evidence and regulatory approval, the ambulatory COVID-19 treatment algorithm has included the antivirals nirmatrelvir plus ritonavir (a boosted SARS-CoV-2 protease inhibitor), molnupiravir, and remdesivir and an ever-evolving (and shrinking) list of monoclonal antibodies.