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Efficacy of Lopinavir-Ritonavir Prophylaxis for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial

22 Pages Posted: 2 Jul 2021

See all articles by Niklaus D. Labhardt

Niklaus D. Labhardt

University of Basel - Department of Infectious Diseases and Hospital Epidemiology

Mikaela Smit

University of Geneva - Division of Infectious Diseases

Ianis Petignat

University of Geneva - Division of Infectious Diseases

Thomas Perneger

Geneva University Hospitals - Division of Clinical Epidemiology

Annalisa Marinosci

Geneva University Hospitals - Division of Infectious Diseases

Piluca Ustero

Geneva University Hospitals - Division of Infectious Diseases

Maria Pia Diniz Ribeiro

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS

Silvio Ragozzino

University of Basel - Department of Infectious Diseases and Hospital Epidemiology

Giovanni Jacopo Nicoletti

University of Basel - Department of Infectious Diseases and Hospital Epidemiology

Pietro Benedetto Faré

University of Southern Switzerland - Division of Infectious Diseases

Diego O. Andrey

Geneva University Hospitals - Division of Infectious Diseases

Frederique Jacquerioz

Geneva University Hospitals - Division and Department of Primary Care

Dan Lebowitz

Geneva University Hospitals - Infection Control Program

Thomas Agoritsas

Geneva University Hospital - Division of General Internal Medicine

Benjamin Meyer

University of Geneva - Centre for Vaccinology

Hervé Spechbach

Geneva University Hospitals - Division and Department of Primary Care

Julien Salamun

Geneva University Hospitals - Division and Department of Primary Care

Idris Guessous

Geneva University Hospitals - Division and Department of Primary Care

François Chappuis

Geneva University Hospitals - Division and Department of Primary Care

Laurent Kaiser

Geneva University Hospitals - Division of Infectious Diseases

Laurent Arthur Decosterd

University of Lausanne - Laboratory of Clinical Pharmacology

Beatriz Grinsztejn

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS

Enos Bernasconi

University of Southern Switzerland - Division of Infectious Diseases

Sandra Wagner Cardoso

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS

Alexandra Calmy

Geneva University Hospitals - Division of Infectious Diseases

The COPEP Study Team

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Abstract

Background: Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19.

Methods: We conducted a pragmatic open-label, parallel, cluster-randomized superiority trial in four sites in Switzerland and Brazil. Clusters were randomized to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). The primary outcome is the occurrence of COVID-19 within 21 days post-enrollment.

Findings: Of 318 participants, 157 (49.4%) were women, median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomized to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76 to 2.73). In the primary endpoint analysis adjusted for propensity score to receive LPV/r, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.53 (95% CI, 0.23 to 1.23, respectively; P =.14).

Interpretation: LPV/r role as PEP for COVID-19 remains unanswered. In this trial, LPV/r over 5 days did not significantly reduce incidence of COVID-19 in exposed individuals. We observed a change in directionality of the effect in favor of LPV/r after adjusting for baseline SARS-CoV-2 PCR results, indicating a potential role of antivirals in COVID-19 prevention.

Clinical Trial Registration Details: ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732.

Funding Information: Fondation privée des HUG and Swiss National Fund (project number: 33IC30_166819).

Declaration of Interests: None reported.

Ethics Approval Statement: The protocol and amendments were approved by Swissmedic and local ethics committees in Switzerland and Brazil. Participants provided written informed consent before study entry.

Suggested Citation

Labhardt, Niklaus D. and Smit, Mikaela and Petignat, Ianis and Perneger, Thomas and Marinosci, Annalisa and Ustero, Piluca and Diniz Ribeiro, Maria Pia and Ragozzino, Silvio and Nicoletti, Giovanni Jacopo and Faré, Pietro Benedetto and Andrey, Diego O. and Jacquerioz, Frederique and Lebowitz, Dan and Agoritsas, Thomas and Meyer, Benjamin and Spechbach, Hervé and Salamun, Julien and Guessous, Idris and Chappuis, François and Kaiser, Laurent and Decosterd, Laurent Arthur and Grinsztejn, Beatriz and Bernasconi, Enos and Cardoso, Sandra Wagner and Calmy, Alexandra and Team, The COPEP Study, Efficacy of Lopinavir-Ritonavir Prophylaxis for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial. Available at SSRN: https://ssrn.com/abstract=3878828 or http://dx.doi.org/10.2139/ssrn.3878828

Niklaus D. Labhardt

University of Basel - Department of Infectious Diseases and Hospital Epidemiology ( email )

Petersplatz 1
Basel, CH-4003
Switzerland

Mikaela Smit

University of Geneva - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

Ianis Petignat

University of Geneva - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

Thomas Perneger

Geneva University Hospitals - Division of Clinical Epidemiology ( email )

Geneva, CH-1211
Switzerland

Annalisa Marinosci

Geneva University Hospitals - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

Piluca Ustero

Geneva University Hospitals - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

Maria Pia Diniz Ribeiro

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS ( email )

Rio de Janeiro
Brazil

Silvio Ragozzino

University of Basel - Department of Infectious Diseases and Hospital Epidemiology ( email )

Petersplatz 1
Basel, CH-4003
Switzerland

Giovanni Jacopo Nicoletti

University of Basel - Department of Infectious Diseases and Hospital Epidemiology ( email )

Petersplatz 1
Basel, CH-4003
Switzerland

Pietro Benedetto Faré

University of Southern Switzerland - Division of Infectious Diseases ( email )

Diego O. Andrey

Geneva University Hospitals - Division of Infectious Diseases

Geneva, CH-1211
Switzerland

Frederique Jacquerioz

Geneva University Hospitals - Division and Department of Primary Care ( email )

Geneva, CH-1211
Switzerland

Dan Lebowitz

Geneva University Hospitals - Infection Control Program ( email )

Geneva, CH-1211
Switzerland

Thomas Agoritsas

Geneva University Hospital - Division of General Internal Medicine ( email )

Geneva, CH-1211
Switzerland

Benjamin Meyer

University of Geneva - Centre for Vaccinology ( email )

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

Hervé Spechbach

Geneva University Hospitals - Division and Department of Primary Care ( email )

Geneva, CH-1211
Switzerland

Julien Salamun

Geneva University Hospitals - Division and Department of Primary Care ( email )

Geneva, CH-1211
Switzerland

Idris Guessous

Geneva University Hospitals - Division and Department of Primary Care ( email )

François Chappuis

Geneva University Hospitals - Division and Department of Primary Care

Geneva, CH-1211
Switzerland

Laurent Kaiser

Geneva University Hospitals - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

Laurent Arthur Decosterd

University of Lausanne - Laboratory of Clinical Pharmacology ( email )

Quartier Chambronne
Lausanne, Vaud CH-1015
Switzerland

Beatriz Grinsztejn

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS ( email )

Rio de Janeiro
Brazil

Enos Bernasconi

University of Southern Switzerland - Division of Infectious Diseases ( email )

Sandra Wagner Cardoso

Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Lab. De Pesquisa Clinica DST/AIDS ( email )

Rio de Janeiro
Brazil

Alexandra Calmy (Contact Author)

Geneva University Hospitals - Division of Infectious Diseases ( email )

Geneva, Shandong
Switzerland

No contact information is available for The COPEP Study Team

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