Oral Nirmatrelvir and Ritonavir for Coronavirus Disease 2019 in Vaccinated, Nonhospitalized Adults Aged 18–50 Years

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The effects of nirmatrelvir/ritonavir (NMV/r [Paxlovid]) on coronavirus disease 2019 (COVID-19) outcomes in younger vaccinated adults are unclear. The objective of this study was to assess if NMV/r use in vaccinated adults aged ≤50 years is associated with improved outcomes and to identify beneficial and nonbeneficial subgroups.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In this cohort study, we generated 2 propensity-matched cohorts of 2547 patients from an 86 119-person cohort assembled from the TriNetX database. Patients in 1 cohort received NMV/r, and patients in the matched control cohort did not. The main outcome was composite of all-cause emergency department visits, hospitalization, and mortality.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The composite outcome was detected in 4.9% of the NMV/r cohort and 7.0% of the non-NMV/r cohort (odds ratio, 0.683 [95% confidence interval, .540–.864]; P = .001), indicating a 30% relative risk reduction. The number needed to treat (NNT) for the primary outcome was 47. Subgroup analyses found significant associations for patients with cancer (NNT = 45), cardiovascular disease (NNT = 30), and both conditions (NNT = 16). No benefit was found for patients with only chronic lower respiratory disorders (asthma/chronic obstructive pulmonary disease [COPD]) or without serious comorbidities. Thirty-two percent of NMV/r prescriptions in the overall database were for 18- to 50-year-olds.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>NMV/r use in vaccinated adults aged 18–50 years, especially with serious comorbidities, was associated with reduced all-cause hospital visits, hospitalization, and mortality in the first 30 days of COVID-19 illness. However, NMV/r in patients without significant comorbidities or with only asthma/COPD had no association of benefit. Therefore, identifying high-risk patients should be a priority and overprescription should be avoided.</jats:p> </jats:sec>