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Original article

The protease inhibitor lopinavir, boosted with ritonavir, as treatment for COVID-19: a rapid review

Jienchi Dorward, Oghenekome Gbinigie, Ting Cai, Nia W Roberts, Nigel Garrett, Gail Hayward, Christopher C Butler

Corresponding author name: Jienchi Dorward
Corresponding author e-mail: Jienchi.Dorward@phc.ox.ac.uk

Citation: Antiviral Therapy 2020; 25:365-376
doi: 10.3851/IMP3385

Date accepted: 05 February 2021
Date published online: 11 March 2021

Abstract

Background: The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19.

Methods: We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Cochrane COVID-19 Study Register, for COVID-19 studies comparing outcomes between patients who did and did not receive lopinavir/ritonavir. The quality of evidence was assessed using the GRADE criteria.

Results: We identified five completed randomized controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5,040 and 2,771 hospitalized adults with COVID-19 found no evidence that lopinavir/ritonavir influenced the primary outcome of mortality, or secondary outcomes including progression to mechanical ventilation or time to discharge. Results remained similar in all sub-group analyses including by age, gender, baseline ventilation and time since symptom onset. The three smaller RCTs (n=86–199) also found no evidence of a benefit in the primary outcomes of time to clinical improvement or time to viral clearance. The 14 observational studies included between 50 and 415 participants, and were limited by a lack of adjustment for potential confounding variables. The majority of these studies found no evidence that lopinavir/ritonavir was associated with improved mortality or other clinical outcomes, although results regarding viral clearance were mixed.

Conclusions: Good evidence from large clinical trials does not support using lopinavir/ritonavir to treat COVID-19 amongst hospitalized patients.

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