Efficacy and safety of lopinavir/ritonavir in the treatment of COVID-19: A systematic review

ABSTRACT

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19.

Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events.

Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment.

Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.

KEYWORDS:

• Coronavirus
• sars virus
• severe acute respiratory syndrome
• pneumonia
• antiviral agents
• lopinavir/ritonavir

Article highlights

• Lopinavir/ritonavir (LPV/r) has shown antiviral activity against Middle Eastern respiratory syndrome (MERS) and severe acute respiratory syndrome coronaviruses (SARS-CoV) as demonstrated by both in vitro and clinical studies.

• LPV/r has been reported in the treatment of patients with COVID-19; however, its effectiveness is not clear.

• The authors systematically reviewed existing clinical literature that reported the use of LPV/r in the treatment of patients with COVID-19 to assess the effectiveness of LPV/r for the treatment of COVID-19.

• Based on this review, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest computed tomography clearance in patients with COVID-19.

Acknowledgments

We acknowledge Karl Holub, Stephen Mead, and Darian Lehmann-Plantenberg for their design and support of the Nested Knowledge meta-analytical software.

Declaration of interest

BA Joseph, NL Reierson, N Mikoff, S Kamrowski, and M Schmidt work for Nested Knowledge and Superior Medical Experts. JM Pederson is employed by Nested Knowledge, Superior Medical Experts, and Marblehead Medical. KM Kallmes works for and holds equity in Nested Knowledge, Superior Medical Experts, and Marblehead Medical. KW Evanson, G Paranjape, AR Davis, JM Pederson, JC Touchette are employed by Superior Medical Experts. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.