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.
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, S. 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, E. 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., Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study, <<FRONTIERS IN MEDICINE>>, 2021; 8 (N/A): N/A-N/A. [doi:10.3389/fmed.2021.639970] [https://hdl.handle.net/10807/338498]
Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study
Costanzo, Simona;Cauda, Roberto;Cingolani, Antonella;Di Gennaro, Salvatore Filippo;Guarnieri, Giorgia;Losito, Angela Raffaella;Maresca, Giancarlo;Mastroianni, Filippo;Mazzitelli, Maria;Musso, Emanuele Massimo;Olivieri, Mirko;Poletti, Valentina;Trecarichi, Enrico Maria;Visconti, Elena;
2021
Abstract
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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