A randomized, controlled, open-label trial of lopinavir–ritonavir in patients with severe COVID-19 shows no benefit for the primary endpoint beyond standard care but shows benefit for some secondary endpoints.
Currently, there are no effective antiviral treatments against the novel coronavirus SARS-CoV-2, the cause of the respiratory illness termed COVID-19. During the outbreak of severe acute respiratory syndrome (SARS) in 2003, in vitro testing identified lopinavir, an HIV aspartate protease inhibitor, to have activity against this virus.
Cao et al. carried out a randomized, controlled, open-label trial for lopinavir–ritonavir (ritonavir helps to stabilize lopinavir) in 199 hospitalized patients with severe COVID-19, of whom 99 were assigned to the treatment group, and 100 received the standard of care. The authors found no benefit of lopinavir–ritonavir time to clinical improvement beyond the standard of care, although lopinavir–ritonavir was found to have benefit for some secondary endpoints, the safety of the treatment was confirmed, and future trials will verify the results.
Background: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking.
Methods: Our study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19.
Results: This study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoint, the rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid, was similar between groups (all p>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest
CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical (P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group.
Conclusion: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care.
Objectives: This study aimed to evaluate the antiviral efficacy of lopinavir/ritonavir alone or combined with arbidol in the treatment of hospitalized patients with common coronavirus disease-19 (COVID-19)
Methods: In this retrospective observational study, COVID-19 hospitalized patients were identified and divided into two groups based on the antiviral agents used during their hospitalization. Group-LR patients were treated with single antiviral drug of lopinavir-ritonavir. Group-LR+Ar patients were treated with lopinavir-ritonavir combined with arbidol for antiviral therapy at least 3 days. Patients were assessed for different clinical outcomes.
Results: A total of 34 and 39 patients were identified for Group-LR and Group-LR+Ar, respectively. Treatment with lopinavir-ritonavir alone was not difference from lopinavir-ritonavir combined with arbidol in overall cure rate of COVID-19 hospitalized patients (92.3% and 97.1%, respectively). In a modified intention-to-treat analysis, lopinavir-ritonavir combined with abidol led to a median time of hospital stay that was shorter by 1.5 days than group-LR (12.5 days vs. 14 days). The percentages of COVID-19 RNA clearance was 92.3 in group-LR and 97.1 in group-LR+Ar. The mean time of virus turning negative was 11.5 plus-or-minus sign 9.0 days in group-LR+Ar that were longer than group-LR. Treatment of lopinavir-ritonavir combined with arbidol did not significantly accelerate main symptoms improvement and promote the image absorption of pulmonary inflammation.
Conclusion: No benefit was observed in the anti-virus effect of lopinavir-ritonavir combined with arbidol compared with lopinavir-ritonavir alone in the hospitalized patients with COVID-19. More clinical observations in COVID-19 patients may help to confirm or exclude the effect of antiviral agents.
An increase of Ct values was 0.9 per day in 2 cases of COVID-19 treated with lopinavir/ritonavir (LPV/r), an increase was 1.0 per day in 3 cases without LPV/r through illness day 1–10, indicating that LPV/r did not shorten the duration of SARS CoV-2 shedding. Cycle threshold (Ct) values are inversely related to the viral RNA copy number. Negative samples have a Ct value of 40, which is the limit of detection.