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

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