Lopinavir-Ritonavir has no effect on COVID-19, complete UK study data show | 2020-10-05

London – Clinical care guidelines recommending the use of HIV / AIDS combinations Lopinavir-Ritonaville Treatment of patients admitted with COVID-19 needs to be updated. The authors of a paper reporting the complete results of a British randomized study showing that antiviral drugs are ineffective in this situation, Lancet October 5th.

There was no significant difference in the primary 28-day mortality endpoint, 22.1% in the lopinavir-ritonavir group, compared to 21.3% with standard treatment (p = 0.58). Results were consistent across different subgroups of patients. There was also no evidence of a risk of progression to mechanical ventilation or a beneficial effect on length of stay, with 69% of the lopinavir-ritonavir group being discharged within 28 days, compared with those who received regular treatment. It was 70% of. The median length of stay for both groups was 11 days.

Between March 19 and June 29, 1,616 patients in the recovery trial were randomized to receive lopinavir-ritonavir, and 3,424 patients received only conventional treatment. Patients taking lopinavir-ritonavir were given lopinavir 400 mg and ritonavir 100 mg orally every 12 hours for 10 days, or until they were discharged earlier. The main result was a 28-day all-cause mortality rate.

Martin Landley, a professor of medicine and epidemiology at Oxford University, who co-leads the recovery trial, said: “Treatment of COVID-19 with a lopinavir-ritonavir drug combination is recommended in many countries, but the results of this study show that it is not an effective treatment for patients admitted with COVID-19. is showing.”

Since preliminary results Published On June 29, the World Health Organization discontinued the lopinavir-ritonavir treatment group in a solidarity trial and reported that interim results were consistent with UK data.

In accompanying comments, China’s Japan-China Friendship Hospital and Metropolitan Medical College, and Bin Khao and Frederick Hayden of the University of Virginia School of Medicine said they compared to the first randomized trial investigating patients’ lopinavir-ritonavir. In COVID-19 conducted by, the size of the lopinavir-ritonavir group in the recovery trial was much larger.

“Therefore, there is more solid evidence of the potential therapeutic effect of lopinavir-ritonavir,” said Cao and Hayden. “The results of these two open-label trials support each other and conclude that lopinavir-ritonavir is not effective in improving outcomes for patients admitted with COVID-19.”

However, Cao and Hayden said they believe that early antiviral treatment for mild cases of COVID-19 and preventive role in high-risk populations after exposure to the virus may still play a role. “Early use of sufficiently potent antivirals is an important determinant of clinical outcome given the association between efficient replication of SARS-CoV-2 immediately after infection and diagnostic mortality and viral RNA loading. “Can be,” they said. ..

Peter Hobby, a professor of emerging infectious diseases and global health at Oxford University and a co-principal researcher for recovery, said: “The results of the recovery test are clear. Combined with the findings from [Cao’s] Interim results from previous small trials and WHO provide strong evidence that lopinavir-ritonavir is not an effective treatment for patients admitted with COVID-19. “

REGN-COV added to recovery

Unfortunately, the HIV / AIDS combination was ineffective, but Hobby said, “These discoveries have allowed us to focus on other promising treatments and know how to treat individual patients. “.

As an example, on September 27th, the Recovery Trial was by Regeneron Pharmaceuticals Inc. Test started. Rain-COV2We will compare the effects of adding antibody cocktails to standard and standard treatments in patients hospitalized with COVID-19.

Like other drugs tested for recovery, this arm of the study assesses the effect of REGN-COV2 on mortality from all causes at 28 days. Other endpoints include shorter hospital stays and the need for ventilation. At least 2,000 patients will be randomly assigned to the REGN-COV2 arm.

REGN-COV2 is the first treatment specifically developed to treat COVID-19 and has been evaluated in a recovery trial that has so far recruited 13,130 patients. This product is based on a new safety profile in humans, preclinical data showing that it can protect against virus escape mutations, and studies of non-human primates showing that it reduced the amount of virus and associated lung damage. Was selected.

Previously, RMAN was looking at whether existing drugs could be reused, but was designed to allow new drugs such as REGN-COV2 to be tested quickly when they become available.

After commenting over the weekend after news that President Donald Trump was treated with REGN-COV2, Landray said that hundreds of patients with relatively mild illness were given the drug in a phase II trial. I pointed out. “But [the trials] It’s too small to know if it will improve patient outcomes, such as shorter hospital stays, reduced ventilator needs, and improved survival, “he said.

“No matter how one man with the disease pays the fare, we need evidence from the trial before we can reach a firm conclusion about this treatment,” Landray said.