Phase 2 study shows 3-drug combo shortens COVID-19 viral shedding

A phase 2 trial has shown that a 2-week course of triple antiviral therapy with (1) interferon beta-1b (used to treat the relapsing-remitting and progressive forms of multiple sclerosis), (2) lopinavir-ritonavir (for the treatment of HIV/AIDS) and (3) ribavirin (used to treat chronic hepatitis C and other flavivirus infections) is safe and better at shortening COVID-19 viral shedding than lopinavir-ritonavir alone (average 7 days vs. 12 days) in patients with mild to moderate illness if treatment is started within 7 days of symptom onset. The study is registered with, NCT04276688.

A Phase 3 study needs to be done and submitted to regulatory agencies for this regimen to be approved. Phase 3 study is a large, properly powered human clinical trial designed to evaluate whether this specific 3-drug combo is better than the other treatment, 2-drug combo, in patients infected with SAR-CoV-2, the coronavirus causing COVID-19.

The prospective study, published in The Lancet, involved 127 adult COVID-19 patients (mean age, 52 years) admitted to six Hong Kong hospitals from February 10 to March 20, 2020. Eighty-six patients were randomly assigned to receive 2 weeks of the triple-drug regimen every 12 hours plus as many as three doses of injectable interferon beta-1b every other day, while 41 received lopinavir-ritonavir alone every 12 hours.

The investigators detected no live coronavirus on nose-throat swabs within, on average, 7 days after the triple-drug combination started, 5 days earlier than with lopinavir-ritonavir alone (hazard ratio, 4.37; 95% confidence interval, 1.86 to 10.24; P = 0.0010). The 3-drug combination also reduced the mean time to complete symptom relief into half (4 versus 8 days) and Sequential Organ Failure Assessment score of 0 (3 versus 8 days) and shortened the mean hospital stay from 14.5 to 9 days.

The findings also suggest that interferon beta 1-b may be a key component of the combination and is worth further investigation for the treatment of COVID-19. Interferons are naturally occurring proteins, produced in response to viral infection and interferon beta-1b could potentially boost the body’s ability to fight SARS-CoV-2.

However, while patients who received the combination therapy within 7 days of symptom onset did better than those in the control group, there was no difference when they were treated 7 or more days after the start of symptoms. The researchers said that the results suggest that the 3-drug combination may minimize the risk of antiviral resistance and decrease risks to healthcare workers by reducing the duration and quantity of viral shedding.



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Dr. Melvin Sanicas

Dr. Melvin Sanicas


Physician 🩺 Scientist 🔬 | Writes about vaccines, viruses, infectious diseases, and global health