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

Dorward, J; Gbinigie, O; Cai, T; Roberts, NW; Garrett, N; Hayward, G; Butler, CC

Journal article

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

Abstract:: Background:
The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesise 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 randomised controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5040 and 2771 hospitalised 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. Results from one of these trials were only available as a pre-print. 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 hospitalised patients.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Dorward, J., Gbinigie, O., Cai, T., Roberts, N. W., Garrett, N., Hayward, G., & Butler, C. C. (2021). The protease inhibitor lopinavir, boosted with ritonavir, as treatment for COVID-19: A rapid review. Antiviral Therapy, 25(7), 365–376.

MLA Style

Dorward, J., et al. “The Protease Inhibitor Lopinavir, Boosted with Ritonavir, as Treatment for COVID-19: A Rapid Review.” Antiviral Therapy, vol. 25, no. 7, International Medical Press, 2021, pp. 365–76.

Chicago Style

Dorward, J, O Gbinigie, T Cai, NW Roberts, N Garrett, G Hayward, and CC Butler. 2021. “The Protease Inhibitor Lopinavir, Boosted with Ritonavir, as Treatment for COVID-19: A Rapid Review.” Antiviral Therapy 25 (7): 365–76.
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