Real-World Effectiveness of Nirmatrelvir/Ritonavir on Coronavirus Disease 2019-Associated Hospitalization Prevention: A Population-based Cohort Study in the Province of Quebec, Canada

Clin Infect Dis. 2023 Sep 18;77(6):805-815. doi: 10.1093/cid/ciad287.

Abstract

Background: Nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron, but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients.

Methods: A retrospective cohort study of outpatients with SARS-CoV-2 between March 15 and 15 October 2022, using data from the Quebec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared with infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk (RR) of COVID-19-associated hospitalization within 30 days was assessed using a Poisson regression.

Results: A total of 8402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced RR of hospitalization (RR: .31; 95% CI: .28; .36; number needed to treat [NNT] = 13). The effect was more pronounced in outpatients with incomplete primary vaccination (RR: .04; 95% CI: .03; .06; NNT = 8), while no benefit was found in those with a complete primary vaccination (RR: .93; 95% CI: .78; 1.08). Subgroups analysis among high-risk outpatients with a complete primary vaccination showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in the RR of hospitalization in severely immunocompromised outpatients (RR: .66; 95% CI: .50; .89; NNT = 16) and in high-risk outpatients aged ≥70 years (RR: .50; 95% CI: .34; .74; NNT = 10) when the last dose of the vaccine was received at least 6 months ago.

Conclusions: Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.

Keywords: COVID-19; SARS-CoV-2; effectiveness; nirmatrelvir; ritonavir.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment
  • COVID-19* / prevention & control
  • Cohort Studies
  • Hospitalization
  • Humans
  • Quebec / epidemiology
  • Retrospective Studies
  • Ritonavir* / therapeutic use
  • SARS-CoV-2

Substances

  • nirmatrelvir
  • Ritonavir
  • Antiviral Agents