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. 2021 Jun 9:8:639970.
doi: 10.3389/fmed.2021.639970. eCollection 2021.

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

Augusto Di Castelnuovo  1 , Simona Costanzo  2 , Andrea Antinori  3 , Nausicaa Berselli  4 , Lorenzo Blandi  5 , Marialaura Bonaccio  2 , Raffaele Bruno  6   7 , Roberto Cauda  8   9 , Alessandro Gialluisi  2 , Giovanni Guaraldi  10 , Lorenzo Menicanti  5 , Marco Mennuni  11 , Ilaria My  12 , Agostino Parruti  13 , Giuseppe Patti  11 , Stefano Perlini  14   15 , Francesca Santilli  16 , Carlo Signorelli  17 , Giulio G Stefanini  12 , Alessandra Vergori  18 , Walter Ageno  19 , Luca Aiello  20 , Piergiuseppe Agostoni  21   22 , Samir Al Moghazi  23 , Rosa Arboretti  24 , Filippo Aucella  25 , Greta Barbieri  26 , Martina Barchitta  27 , Alessandro Bartoloni  28 , Carolina Bologna  29 , Paolo Bonfanti  30   31 , Lucia Caiano  19 , Laura Carrozzi  32 , Antonio Cascio  33 , Giacomo Castiglione  34 , Mauro Chiarito  12 , Arturo Ciccullo  8 , Antonella Cingolani  8   9 , Francesco Cipollone  16 , Claudia Colomba  33 , Crizia Colombo  11 , Francesco Crosta  13 , Giovanni Dalena  35 , Chiara Dal Pra  36 , Gian Battista Danzi  37 , Damiano D'Ardes  16 , Katleen de Gaetano Donati  8 , Francesco Di Gennaro  38 , Giuseppe Di Tano  37 , Gianpiero D'Offizi  39 , Tommaso Filippini  4 , Francesco Maria Fusco  40 , Carlo Gaudiosi  41 , Ivan Gentile  42 , Giancarlo Gini  19 , Elvira Grandone  25 , Gabriella Guarnieri  43 , Gennaro L F Lamanna  35 , Giovanni Larizza  35 , Armando Leone  44 , Veronica Lio  11 , Angela Raffaella Losito  8 , Gloria Maccagni  37 , Stefano Maitan  20 , Sandro Mancarella  45 , Rosa Manuele  46 , Massimo Mapelli  21   22 , Riccardo Maragna  21   22 , Lorenzo Marra  44 , Giulio Maresca  47 , Claudia Marotta  38 , Franco Mastroianni  35 , Maria Mazzitelli  48 , Alessandro Mengozzi  26 , Francesco Menichetti  26 , Jovana Milic  10 , Filippo Minutolo  49 , Beatrice Molena  43 , R Mussinelli  15 , Cristina Mussini  10 , Maria Musso  50 , Anna Odone  17 , Marco Olivieri  51 , Emanuela Pasi  52 , Annalisa Perroni  16 , Francesco Petri  30 , Biagio Pinchera  42 , Carlo A Pivato  12 , Venerino Poletti  53 , Claudia Ravaglia  53 , Marco Rossato  36 , Marianna Rossi  30 , Anna Sabena  14 , Francesco Salinaro  14 , Vincenzo Sangiovanni  40 , Carlo Sanrocco  13 , Laura Scorzolini  54 , Raffaella Sgariglia  45 , Paola Giustina Simeone  13 , Michele Spinicci  28 , Enrico Maria Trecarichi  48 , Giovanni Veronesi  19 , Roberto Vettor  36 , Andrea Vianello  43 , Marco Vinceti  4   55 , Elena Visconti  8 , Laura Vocciante  47 , Raffaele De Caterina  32 , Licia Iacoviello  2   19 ; COVID-19 RISK and Treatments (CORIST) Collaboration
Affiliations

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

Augusto Di Castelnuovo et al. Front Med (Lausanne). .

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.

Keywords: COVID-19; SARS-CoV-2; darunavir; in-hospital mortality; lopinavir.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Survival curves according to lopinavir/ritonavir or darunavir/cobicistat use. The curves are adjusted by propensity score analysis (inverse probability by treatment weighting) and hospitals clustering as random effect, and are generated using the first imputed dataset. The other imputed datasets are similar and thus omitted.
See this image and copyright information in PMC

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