Efficacy and Safety of Lopinavir/Ritonavir for Treatment of COVID-19: A Systematic Review and Meta-Analysis

  1. Saad Alhumaid
  2. Abbas Al Mutair
  3. Zainab Al Alawi
  4. Naif Alhmeed
  5. Abdul Rehman Zia Zaidi
  6. Mansour Tobaiqy

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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, I2 = 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.

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  1. Version published to 10.3390/tropicalmed5040180
  2. ScreenIT

    SciScore for 10.1101/2020.06.16.20133298: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationRisk of biased evaluation of included studies: The quality assessment of the studies was undertaken based on the revised Cochrane risk of bias tool (RoB 2.0) for randomized controlled studies [20].
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    This systematic review was conducted with reference to the basics of Cochrane Handbook for Systematic Reviews of
    Cochrane Handbook
    suggested: None
    Published articles from December 1, 2019 to May 22, 2020 were selected for review from 8 electronic databases (PubMed, CINAHL, Embase,
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    , Proquest, Wiley online library, Medline, and Nature).
    Proquest
    suggested: (ProQuest, RRID:SCR_006093)
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    Review Manager (Version 5.3, Oxford, UK; The Cochrane Collaboration, 2014) was used to conduct all statistical analyses and generate the forest plots [18].
    Cochrane Collaboration
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The key limitations of this study were the limited number of clinical studies investigating the efficacy and safety of lopinavir/ritonavir combination with the limited number of participants. Another limitation is inability to perform any type of meta-analysis specifically for the results of efficacy and safety of using lopinavir/ritonavir in combination with other agents versus no antiviral therapy (conventional therapy) or control because of the large methodological differences. Despite these limitations, this systematic review provided valuable insight into the efficacy, safety, and clinical outcomes of lopinavir/ritonavir alone or with other antiviral medications.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.16.20133298v1 on medRxiv