*Review* **<sup>E</sup>**ffi**cacy and Safety of Lopinavir**/**Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis**

#### **Saad Alhumaid 1,\*, Abbas Al Mutair 2, Zainab Al Alawi 3, Naif Alhmeed 4, Abdul Rehman Zia Zaidi 5 and Mansour Tobaiqy 6**


Received: 22 October 2020; Accepted: 26 November 2020; Published: 28 November 2020

**Abstract:** (Background) Lopinavir-ritonavir (LPV/RTV) is a human immunodeficiency virus (HIV) antiviral combination that has been considered for the treatment of COVID-19 disease. (Aim) This systematic review aimed to assess the efficacy and safety of LPV/RTV in COVID-19 patients in the published research. (Methods) A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Articles were selected for review from 8 electronic databases. This review evaluated the effects of LPV/RTV alone or in combination with standard care ± interferons/antiviral treatments compared to other therapies, regarding duration of hospital stay, risk of progressing to invasive mechanical, time to virological cure and body temperature normalization, cough relief, radiological progression, mortality and safety. (Results) A consensus was reached to select 32 articles for full-text screening; only 14 articles comprising 9036 patients were included in this study; and eight of these were included for meta-analysis. Most of these studies did not report positive clinical outcomes with LPV/RTV treatment. In terms of virological cure, three studies reported less time in days to achieve a virological cure for LPV/RTV arm relative to no antiviral treatment (−0.81 day; 95% confidence interval (CI), −4.44 to 2.81; *p* = 0.007, *I*2 = 80%). However, the overall effect was not significant (*p* = 0.66). When comparing the LPV/RTV arm to umifenovir arm, a favorable affect was observed for umifenovir arm, but not statically significant (*p* = 0.09). In terms of time to body normalization and cough relief, no favorable effects of LPV/RTV versus umifenovir were observed. The largest trials (RECOVERY and SOLIDARITY) have shown that LPV/RTV failed to reduce mortality, initiation of invasive mechanical ventilation or hospitalization duration. Adverse events were reported most frequently for LPV/RTV (*n* = 84) relative to other antivirals and no antiviral treatments. (Conclusions) This review did not reveal any significant advantage in efficacy of LPV/RTV for the treatment of COVID-19 over standard care, no antivirals or other antiviral treatments. This result might not reflect the actual evidence.

**Keywords:** COVID-19; efficacy; safety; kaletra; lopinavir/ritonavir; meta-analysis
