Summary of COVID-19 lopinavir/ritonavir studies


1. Cao et al., A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
199 patient lopinavir/ritonavir late treatment RCT: 23% lower mortality (p=0.39), 29% greater improvement (p=0.19), and 4% improved viral clearance (p=1).
RCT 199 hospitalized COVID-19 patients showing no significant difference with lopinavir-ritonavir treatment. 28-day mortality was lower in the treatment group, without statistical significance. 3 treatment patients died within 24 hours after randomization and did not receive lopinavir-ritonavir. No significant difference was found in viral RNA load over time between the groups.
May 2020, New England J. Medicine, http://www.nejm.org/doi/10.1056/NEJMoa2001282, https://c19p.org/cao4

2. Yan et al., Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection
120 patient lopinavir/ritonavir late treatment study: 40% improved viral clearance (p=0.01).
Retrospective 120 hospitalized non-critically ill COVID-19 patients showing that early administration of lopinavir/ritonavir was associated with shorter duration of SARS-CoV-2 RNA shedding.
May 2020, European Respiratory J., https://publications.ersnet.org/lookup/doi/10.1183/13993003.00799-2020, https://c19p.org/yan8

3. Di Castelnuovo et al., Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
2,972 patient lopinavir/ritonavir late treatment study: 6% lower mortality (p=0.52).
Retrospective 3,451 hospitalized COVID-19 patients in Italy showing higher mortality with darunavir/cobicistat.
Jun 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.639970/full, https://c19p.org/dicastelnuovo3lpv

4. SOLIDARITY Trial Consortium et al., Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
2,771 patient lopinavir/ritonavir late treatment RCT: no change in mortality (p=1) and 2% higher ventilation (p=0.89).
WHO SOLIDARITY open-label RCT showing no significant difference in outcomes with lopinavir/ritonavir treatment.
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidaritylpv

5. Ader et al., An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-beta-1a and hydroxychloroquine in hospitalized patients with COVID-19 - Final results from the DisCoVeRy trial
296 patient lopinavir/ritonavir late treatment RCT: 36% higher mortality (p=0.39) and 26% improved viral clearance (p=0.65).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial showing no significant differences with lopinavir/ritonavir.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discoverylpv

6. Zhou et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
137 patient lopinavir/ritonavir late treatment study: 10% slower viral clearance (p=0.06).
Retrospective 191 hospitalized COVID-19 patients in China showing no significant difference in viral clearance with lopinavir/ritonavir.
Mar 2020, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673620305663, https://c19p.org/zhou24

7. Değirmenci et al., Is vitamin D level important in pregnant women with COVID-19?
125 patient lopinavir/ritonavir late treatment study: 136% higher hospitalization (p=0.43).
Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencihlpv

8. Wen et al., The efficacy and safety of lopinavir/ritonavir and arbidol in patients with coronavirus disease 2019
117 patient lopinavir/ritonavir late treatment study: 21% slower viral clearance (p=0.008).
Retrospective 178 hospitalized COVID-19 patients in China
Jul 2020, Zhonghua Nei Ke Za Zhi, https://pubmed.ncbi.nlm.nih.gov/32388937/, https://c19p.org/wen4

9. Labhardt et al., Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial
318 patient lopinavir/ritonavir prophylaxis RCT: 630% higher progression (p=0.02) and 40% fewer symptomatic cases (p=0.17).
Open-label, cluster-randomized RCT 318 asymptomatic close contacts in Switzerland and Brazil showing no statistically significant difference in symptomatic COVID-19 at 21 days with LPV/r prophylaxis. The mid-trial changes in allocation and 10-month recruitment window introduces potential calendar-time confounding - e.g., if community incidence fell over time, this may over-represent lower-risk weeks in the LPV/r arm, thereby overestimating efficacy. Authors reports 2 hospitalizations but do not specify which group the patients were in.
Dec 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021004697, https://c19p.org/labhardt

10. Kokturk et al., The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients
1,500 patient lopinavir/ritonavir late treatment study: 118% higher mortality (p=0.38).
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference in mortality with treatment.
Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturklpv

11. Wong et al., Slower Recovery with Early Lopinavir/Ritonavir use in Pediatric COVID-19 Patients: A Retrospective Observational Study
933 patient lopinavir/ritonavir early treatment study: 96% lower hospital discharge (p<0.0001) and 96% worse recovery (p<0.0001).
Retrospective 933 pediatric COVID-19 patients in Hong Kong showing worse outcomes with early lopinavir/ritonavir (LPV/r) use.
Apr 2022, Pediatric Drugs, https://link.springer.com/10.1007/s40272-022-00500-7, https://c19p.org/wong7

12. Horby et al., Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
5,040 patient lopinavir/ritonavir late treatment RCT: 7% higher mortality (p=0.24), 15% higher ventilation (p=0.15), and 2% lower hospital discharge (p=0.53).
RCT 1,616 hospitalized COVID-19 patients showing no significant differences with lopinavir-ritonavir treatment compared to usual care. 6-month results are from [Horby]
Oct 2020, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673620320134, https://c19p.org/horby2

13. Lowe et al., Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 × 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19
120 patient lopinavir/ritonavir early treatment RCT: 200% higher hospitalization (p=1) and 7% improved viral clearance (p=0.56).
240 patient RCT comparing favipiravir, favipiravir + LPV/r, LPV/r, and placebo, showing improved viral clearance with favipiravir, but no significant difference for LPV/r. Efficacy was lower in the combined favipiravir + LPV/r arm, where plasma levels of favipiravir were lower. Favipiravir 1800mg twice daily on day 1 followed by 400mg four times daily on days 2-7.
Feb 2022, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004120, https://c19p.org/lowelpv

14. Huang et al., No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study
65 patient lopinavir/ritonavir early treatment RCT: 6% longer hospitalization (p=0.68), 33% faster recovery (p=0.32), 18% faster improvement (p=0.07), and 15% slower viral clearance (p=0.41).
RCT 101 mild to moderate COVID-19 patients showing no significant difference in antiviral effectiveness among three treatment regimens: ribavirin plus interferon-alpha, lopinavir/ritonavir plus interferon-alpha, and ribavirin plus lopinavir/ritonavir plus interferon-alpha.
Jul 2020, Frontiers in Pharmacology, https://www.frontiersin.org/article/10.3389/fphar.2020.01071/full, https://c19p.org/huang17

15. Reis et al., Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial
471 patient lopinavir/ritonavir late treatment RCT: 86% higher mortality (p=1) and 16% higher hospitalization (p=0.72).
Early terminated RCT in Brazil showing no significant differences with lopinavir/ritonavir treatment.
Apr 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044, https://c19p.org/reislpv

16. Kaizer et al., Lopinavir/ritonavir for treatment of non-hospitalized patients with COVID-19: a randomized clinical trial
446 patient lopinavir/ritonavir late treatment RCT: 203% higher mortality (p=0.49), 20% higher hospitalization (p=0.78), and 3% worse recovery (p=0.88).
RCT 437 non-hospitalized COVID-19 patients showing no significant differences with lopinavir/ritonavir (LPV/r) treatment.
Mar 2023, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222006658, https://c19p.org/kaizer

17. Li et al., Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial
51 patient lopinavir/ritonavir late treatment RCT: 100% higher progression (p=0.46) and 3% faster viral clearance (p=0.84).
RCT 86 mild/moderate COVID-19 patients showing no significant difference in outcomes with lopinavir/ritonavir or arbidol compared to control.
Dec 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300015, https://c19p.org/li44