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

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

Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study

109nononeBackground: 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.noneDi Castelnuovo A.; Costanzo S.; Antinori A.; Berselli N.; Blandi L.; Bonaccio M.; Bruno R.; Cauda R.; Gialluisi A.; Guaraldi G.; Menicanti L.; Mennuni M.; My I.; Parruti A.; Patti G.; Perlini S.; Santilli F.; Signorelli C.; Stefanini G.G.; Vergori A.; Ageno W.; Aiello L.; Agostoni P.; Moghazi S.A.; Arboretti R.; Aucella F.; Barbieri G.; Barchitta M.; Bartoloni A.; Bologna C.; Bonfanti P.; Caiano L.; Carrozzi L.; Cascio A.; Castiglione G.; Chiarito M.; Ciccullo A.; Cingolani A.; Cipollone F.; Colomba C.; Colombo C.; Crosta F.; Dalena G.; Dal Pra C.; Danzi G.B.; D'ardes D.; Donati K.G.; Di Gennaro F.; Di Tano G.; D'offizi G.; Filippini T.; Fusco F.M.; Gaudiosi C.; Gentile I.; Gini G.; Grandone E.; Guarnieri G.; Lamanna G.L.F.; Larizza G.; Leone A.; Lio V.; Losito A.R.; Maccagni G.; Maitan S.; Mancarella S.; Manuele R.; Mapelli M.; Maragna R.; Marra L.; Maresca G.; Marotta C.; Mastroianni F.; Mazzitelli M.; Mengozzi A.; Menichetti F.; Milic J.; Minutolo F.; Molena B.; Mussinelli R.; Mussini C.; Musso M.; Odone A.; Olivieri M.; Pasi E.; Perroni A.; Petri F.; Pinchera B.; Pivato C.A.; Poletti V.; Ravaglia C.; Rossato M.; Rossi M.; Sabena A.; Salinaro F.; Sangiovanni V.; Sanrocco C.; Scorzolini L.; Sgariglia R.; Simeone P.G.; Spinicci M.; Trecarichi E.M.; Veronesi G.; Vettor R.; Vianello A.; Vinceti M.; Visconti E.; Vocciante L.; Caterina R.D.; Iacoviello L.Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Bruno, R.; Cauda, R.; Gialluisi, A.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; My, I.; Parruti, A.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G. G.; Vergori, A.; Ageno, W.; Aiello, L.; Agostoni, P.; Moghazi, S. A.; Arboretti, R.; Aucella, F.; Barbieri, G.; Barchitta, M.; Bartoloni, A.; Bologna, C.; Bonfanti, P.; Caiano, L.; Carrozzi, L.; Cascio, A.; Castiglione, G.; Chiarito, M.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crosta, F.; Dalena, G.; Dal Pra, C.; Danzi, G. B.; D'Ardes, D.; Donati, K. G.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Filippini, T.; Fusco, F. M.; Gaudiosi, C.; Gentile, I.; Gini, G.; Grandone, E.; Guarnieri, G.; Lamanna, G. L. F.; Larizza, G.; Leone, A.; Lio, V.; Losito, A. R.; Maccagni, G.; Maitan, S.; Mancarella, S.; Manuele, R.; Mapelli, M.; Maragna, R.; Marra, L.; Maresca, G.; Marotta, C.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Milic, J.; Minutolo, F.; Molena, B.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Perroni, A.; Petri, F.; Pinchera, B.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Rossato, M.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Trecarichi, E. M.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, M.; Visconti, E.; Vocciante, L.; Caterina, R. D.; Iacoviello, L