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

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

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.