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

摘要

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 I sup2/sup 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), I sup2/sup = 0, virological cure RR: 1.06 (95 CI: 0.85, 1.31), I sup2/sup = 0, radiological improvement RR: 0.81 (95 CI: 0.62, 1.05) and adverse events RR: 2.59 (95 CI: 0.17, 38.90), I sup2/sup = 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); I sup2/sup = 0. Conclusion There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.