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

https://doi.org/10.1016/j.jiph.2021.03.015Get rights and content
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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

Lopinavir
Ritonavir
COVID-19
Virological cure
Safety
Meta-analysis

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