Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials

J Infect Public Health. 2021 Jun;14(6):740-748. doi: 10.1016/j.jiph.2021.03.015. Epub 2021 Apr 20.

Abstract

Background: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated.

Methods: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test.

Results: Out of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%].

Conclusion: There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Keywords: COVID-19; Lopinavir; Meta-analysis; Ritonavir; Safety; Virological cure.

Publication types

  • Systematic Review

MeSH terms

  • Antiviral Agents / adverse effects
  • COVID-19 Drug Treatment*
  • Humans
  • Lopinavir / adverse effects
  • Randomized Controlled Trials as Topic
  • Ritonavir* / adverse effects
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Lopinavir
  • Ritonavir