Nirmatrelvir/ritonavir or Molnupiravir for treatment of non-hospitalized patients with COVID-19 at risk of disease progression

PLoS One. 2024 Jun 6;19(6):e0298254. doi: 10.1371/journal.pone.0298254. eCollection 2024.

Abstract

Background: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents.

Methods: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups.

Results: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group.

Conclusion: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • Betacoronavirus
  • COVID-19 Drug Treatment*
  • COVID-19* / epidemiology
  • COVID-19* / mortality
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / mortality
  • Cytidine* / analogs & derivatives
  • Cytidine* / therapeutic use
  • Disease Progression*
  • Female
  • Hospitalization*
  • Humans
  • Hydroxylamines* / therapeutic use
  • Indoles / therapeutic use
  • Lactams
  • Leucine* / analogs & derivatives
  • Leucine* / therapeutic use
  • Male
  • Middle Aged
  • Nitriles
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / virology
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Risk Factors
  • Ritonavir* / therapeutic use
  • SARS-CoV-2* / isolation & purification

Substances

  • molnupiravir
  • Ritonavir
  • Hydroxylamines
  • Cytidine
  • Antiviral Agents
  • Leucine
  • nirmatrelvir
  • Proline
  • Indoles
  • Lactams
  • Nitriles