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

Link to article at PubMed

Antivir Ther. 2021 Mar 11. doi: 10.3851/IMP3385. Online ahead of print.

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.

PMID:33704086 | DOI:10.3851/IMP3385

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