Lopinavir/r is thought to inhibit the 3-chymotrypsin-like protease of coronaviruses. To achieve appropriate plasma levels, it has to be boosted with another HIV PI called ritonavir (usually indicated by “/r”: lopinavir/r). Due to some uncontrolled trials in SARS and MERS, lopinavir/r was widely used in the first months, despite the lack of any evidence. In an early retrospective study on 280 cases, early initiation of lopinavir/r and/or ribavirin showed some benefits (Wu 2020).

  • The first open-label RCT in 199 adults hospitalized with severe COVID-19 did not find any clinical benefit beyond standard of care in patients receiving the drug 10 to 17 days after onset of illness (Cao 2020). There was no discernible effect on viral shedding.
  • A Phase II, multicentre, open-label RCT from Hong Kong randomized 127 patients with mild-to-moderate COVID-19 (median 5 days from symptom onset) to receive lopinavir/r only or a triple combination consisting of lopinavir/r, ribavirin and interferon (Hung 2020). The results indicate that the triple combination can be beneficial when started early (see below, interferon). As there was no lopinavir/r-free control group, this trial does not prove lopinavir/r efficacy.
  • After preliminary results were made public on June 29, 2020, we are now facing the full paper on the lopinavir/r arm in the RECOVERY trial: In 1,616 patients admitted to hospital who were randomly allocated to receive lopinavir/r (3,424 patients received usual care), lopinavir/r had no benefit. Overall, 374 (23%) patients allocated to lopinavir/r and 767 (22%) patients allocated to usual care died within 28 days. Results were consistent across all prespecified subgroups. No significant difference in time until discharge alive from hospital (median 11 days in both groups) or the proportion of patients discharged from hospital alive within 28 days was found. Although the lopinavir/r, dexamethasone, and hydroxychloroquine groups have now been stopped, the RECOVERY trial continues to study the effects of azithromycin, tocilizumab, convalescent plasma, and REGN-CoV2.

At least two studies suggested that lopinavir pharmacokinetics in COVID-19 patients may differ from those seen in HIV-infected patients. In both studies, very high concentrations were observed, exceeding those in HIV-infected patients by 2-3 fold (Schoergenhofer 2020, Gregoire 2020). However, concentrations of protein-unbound lopinavir achieved by current HIV dosing is probably still too low for inhibiting SARS-CoV-2 replication. The EC50 for HIV is much lower than for SARS-CoV-2. It remains to be seen whether these levels will be sufficient for (earlier) treatment of mild cases or as post-exposure prophylaxis.

Find the entire treatment chapter at https://covidreference.com/treatment



AcalabrutinibAnticomplement therapiesAzithromycinCamostatChloroquineColchicineConvalescent plasmaCorticosteroidsCytokine blockersFamotidineFavipiravirG-CSFHuman recombinant soluble ACE2HydroxychloroquineIbrutinibIloprostInterferonsJAK inhibitorsLeflunomideLopinavirMonoclonal antibodiesN-acetylcysteineOseltamivir(other) Protease inhibitors(other) RdRp inhibitorsREGN-COV2Umifenovir

Outlook | References

By Christian Hoffmann