No Observable Benefits of Lopinavir-Ritonavir for Severe COVID-19

The treatment was no better than standard care.

Bin Cao, MD

The article, “Lopinavir-Ritonavir Not Better than Standard Care for COVID-19 Patients,” was originally published on ContagionLive.

Recent study findings showed that there were no observable benefits of lopinavir-ritonavir treatment for patients with severe coronavirus disease 2019 (COVID-19) compared to standard care.

Currently, no therapeutics have proven effective against severe COVID-19, leading a team investigators from China conducted a randomized, controlled trial involving 199 patients with laboratory-confirmed coronavirus. Lopinavir is an HIV drug which has shown in vitro inhibitory activity against SARS-CoV-2. Ritonavir can be combined with lopinavir to increase its plasma half-life, Bin Cao, MD, and colleagues wrote.

There were 99 patients randomized to receive lopinavir-ritonavir 400 mg/100 mg twice daily for 14 days plus standard care. However, 5 patients in this group did not receive any doses of lopinavir-ritonavir because of 3 early deaths within 24 hours after randomization and 2 others whose attending physician refused to prescribe lopinavir-ritonavir following randomization.

The 100 other patients in the study received standard care alone. The investigators aimed to measure time to clinical improvement and hospital discharge, whichever came first.

The investigators found that the median interval time between symptom onset and randomization was 13 days. They added that there were no major differences between the two groups. The median age of the patients was 58 years and 60% of the patients were men.

Patients that received lopinavir-ritonavir did not have a time to clinical improvement different from the patients who received standard care only, the investigators found. Those treated with lopinavir-ritonavir had a 15-day median time to clinical improvement, compared to 16 days in the standard care group.

Investigators observed no differences between the groups on the time to clinical deterioration, which they defined as a one-category increase on a seven-category scale.

However, the Cao and the team did find that the 28-day mortality was numerically lower in the lopinavir-ritonavir-treated group compared to the standard care-only group (19% vs 25%).

The patients treated with lopinavir-ritonavir were also found to have a shorter stay in the intensive care unit compared to standard care patients (6 days vs 11 days). The intervention group also had shorter duration from randomization to hospital discharge compared to the standard care cohort (12 days vs 14 days), investigators found.

Additionally, the team found that on day 14, a higher percentage of lopinavir-ritonavir-treated patients showed clinical improvement compared to the standard care group (45% vs 30%). But duration of oxygen therapy, duration of hospitalization, and time from randomization to death measures showed no differences between the groups, the study authors added.

Half of the lopinavir-ritonavir patients and half of the standard care patients reported adverse events in the time between randomization and day 28 including nausea, vomiting, and diarrhea. These gastrointestinal events were more common in the lopinavir-ritonavir patients, investigators noted.

Four gastrointestinal events were observed in the lopinavir-ritonavir patients but none in the standard care group. Cao and the investigators judged all of these serious adverse events to be related to the lopinavir-ritonavir treatment. The deaths that occurred within the study period were all COVID-19-related.

“We found that lopinavir-ritonavir treatment did not significantly accelerate clinical improvement, reduce mortality, or diminish throat viral RNA detectability in patients with serious Covid-19,” Cao and the team concluded. “These early data should inform future studies to assess this and other medication in the treatment of infection with SARS-CoV-2.”

The study, “A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19,” was published online in The New England Journal of Medicine.