Frontiers in Medicine (Jun 2021)

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

  • Augusto Di Castelnuovo,
  • Simona Costanzo,
  • Andrea Antinori,
  • Nausicaa Berselli,
  • Lorenzo Blandi,
  • Marialaura Bonaccio,
  • Raffaele Bruno,
  • Raffaele Bruno,
  • Roberto Cauda,
  • Roberto Cauda,
  • Alessandro Gialluisi,
  • Giovanni Guaraldi,
  • Lorenzo Menicanti,
  • Marco Mennuni,
  • Ilaria My,
  • Agostino Parruti,
  • Giuseppe Patti,
  • Stefano Perlini,
  • Stefano Perlini,
  • Francesca Santilli,
  • Carlo Signorelli,
  • Giulio G. Stefanini,
  • Alessandra Vergori,
  • Walter Ageno,
  • Luca Aiello,
  • Piergiuseppe Agostoni,
  • Piergiuseppe Agostoni,
  • Samir Al Moghazi,
  • Rosa Arboretti,
  • Filippo Aucella,
  • Greta Barbieri,
  • Martina Barchitta,
  • Alessandro Bartoloni,
  • Carolina Bologna,
  • Paolo Bonfanti,
  • Paolo Bonfanti,
  • Lucia Caiano,
  • Laura Carrozzi,
  • Antonio Cascio,
  • Giacomo Castiglione,
  • Mauro Chiarito,
  • Arturo Ciccullo,
  • Antonella Cingolani,
  • Antonella Cingolani,
  • Francesco Cipollone,
  • Claudia Colomba,
  • Crizia Colombo,
  • Francesco Crosta,
  • Giovanni Dalena,
  • Chiara Dal Pra,
  • Gian Battista Danzi,
  • Damiano D'Ardes,
  • Katleen de Gaetano Donati,
  • Francesco Di Gennaro,
  • Giuseppe Di Tano,
  • Gianpiero D'Offizi,
  • Tommaso Filippini,
  • Francesco Maria Fusco,
  • Carlo Gaudiosi,
  • Ivan Gentile,
  • Giancarlo Gini,
  • Elvira Grandone,
  • Gabriella Guarnieri,
  • Gennaro L. F. Lamanna,
  • Giovanni Larizza,
  • Armando Leone,
  • Veronica Lio,
  • Angela Raffaella Losito,
  • Gloria Maccagni,
  • Stefano Maitan,
  • Sandro Mancarella,
  • Rosa Manuele,
  • Massimo Mapelli,
  • Massimo Mapelli,
  • Riccardo Maragna,
  • Riccardo Maragna,
  • Lorenzo Marra,
  • Giulio Maresca,
  • Claudia Marotta,
  • Franco Mastroianni,
  • Maria Mazzitelli,
  • Alessandro Mengozzi,
  • Francesco Menichetti,
  • Jovana Milic,
  • Filippo Minutolo,
  • Beatrice Molena,
  • R. Mussinelli,
  • Cristina Mussini,
  • Maria Musso,
  • Anna Odone,
  • Marco Olivieri,
  • Emanuela Pasi,
  • Annalisa Perroni,
  • Francesco Petri,
  • Biagio Pinchera,
  • Carlo A. Pivato,
  • Venerino Poletti,
  • Claudia Ravaglia,
  • Marco Rossato,
  • Marianna Rossi,
  • Anna Sabena,
  • Francesco Salinaro,
  • Vincenzo Sangiovanni,
  • Carlo Sanrocco,
  • Laura Scorzolini,
  • Raffaella Sgariglia,
  • Paola Giustina Simeone,
  • Michele Spinicci,
  • Enrico Maria Trecarichi,
  • Giovanni Veronesi,
  • Roberto Vettor,
  • Andrea Vianello,
  • Marco Vinceti,
  • Marco Vinceti,
  • Elena Visconti,
  • Laura Vocciante,
  • Raffaele De Caterina,
  • Licia Iacoviello,
  • Licia Iacoviello,
  • The COVID-19 RISK and Treatments (CORIST) Collaboration

DOI
https://doi.org/10.3389/fmed.2021.639970
Journal volume & issue
Vol. 8

Abstract

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Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

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