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 I 2 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 2 = 0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I 2 = 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 2 = 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 2 = 0%]. Conclusion There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Lopinavir/Ritonavir for COVID-19: a Systematic Review and Meta-Analysis

“…Similar to the findings of Tobaiqy et al (38), our meta-analysis found higher adverse events in the lopinavir/ritonavir group compared with the control group. Also, in a study conducted by Patel et al (41), there was no difference in patients treated with lopinavir-ritonavir than supportive care, consistent with our study. A significant difference was observed between lopinavir/ritonavir and control groups for adverse events in the studies Tobaiqy et al (38) and Patel et al (41) authors observed more adverse events in lopinavir/ritonavir versus arbidol.…”

Antiviral Therapeutic Approaches for SARS-CoV-2 Infection: A Systematic Review

“…These results are consistent with those of a meta-analysis published online in April 2021 where the differences between lopinavir/ritonavir group and those receiving standard therapy were not statistically significant in terms of mortality, viral clearance (RR = 1.06; 95% CI = 0.85–1.31) and radiological improvement (RR = 0.81; 95% CI = 0.62–1.05) [ 89 ].…”

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review

“…In contrast, drugs including lopinavir/ritonavir were associated with 4 × higher odds of liver injury ( 21 ). Of course it is noteworthy to imply that the efficacy of lopinavir/ritonavir in COVID-19 patients is still under question and should be evaluated in further studies ( 42 , 43 ).…”