Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
Authors: Di Castelnuovo Augusto , Costanzo Simona , Antinori Andrea , Berselli Nausicaa , Blandi Lorenzo , Bonaccio Marialaura , Bruno Raffaele , Cauda Roberto , Gialluisi Alessandro , Guaraldi Giovanni , Menicanti Lorenzo , Mennuni Marco , My Ilaria , Parruti Agostino , Patti Giuseppe , Perlini Stefano , Santilli Francesca , Signorelli Carlo , Stefanini Giulio G. , Vergori Alessandra , Ageno Walter , Aiello Luca , Agostoni Piergiuseppe , Al Moghazi Samir , Arboretti Rosa , Aucella Filippo , Barbieri Greta , Barchitta Martina , Bartoloni Alessandro , Bologna Carolina , Bonfanti Paolo , Caiano Lucia , Carrozzi Laura , Cascio Antonio , Castiglione Giacomo , Chiarito Mauro , Ciccullo Arturo , Cingolani Antonella , Cipollone Francesco , Colomba Claudia , Colombo Crizia , Crosta Francesco , Dalena Giovanni , Dal Pra Chiara , Danzi Gian Battista , D'Ardes Damiano , de Gaetano Donati Katleen , Di Gennaro Francesco , Di Tano Giuseppe , D'Offizi Gianpiero , Filippini Tommaso , Maria Fusco Francesco , Gaudiosi Carlo , Gentile Ivan , Gini Giancarlo , Grandone Elvira , Guarnieri Gabriella , Lamanna Gennaro L. F. , Larizza Giovanni , Leone Armando , Lio Veronica , Losito Angela Raffaella , Maccagni Gloria , Maitan Stefano , Mancarella Sandro , Manuele Rosa , Mapelli Massimo , Maragna Riccardo , Marra Lorenzo , Maresca Giulio , Marotta Claudia , Mastroianni Franco , Mazzitelli Maria , Mengozzi Alessandro , Menichetti Francesco , Milic Jovana , Minutolo Filippo , Molena Beatrice , Mussinelli R. , Mussini Cristina , Musso Maria , Odone Anna , Olivieri Marco , Pasi Emanuela , Perroni Annalisa , Petri Francesco , Pinchera Biagio , Pivato Carlo A. , Poletti Venerino , Ravaglia Claudia , Rossato Marco , Rossi Marianna , Sabena Anna , Salinaro Francesco , Sangiovanni Vincenzo , Sanrocco Carlo , Scorzolini Laura , Sgariglia Raffaella , Simeone Paola Giustina , Spinicci Michele , Trecarichi Enrico Maria , Veronesi Giovanni , Vettor Roberto , Vianello Andrea , Vinceti Marco , Visconti Elena , Vocciante Laura , De Caterina Raffaele , Iacoviello Licia ,   The COVID-19 RISK and Treatments (CORIST) Collaboration
Published: June 2021

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.