Results from a randomised trial for treating COVID-19 with a two week triple drug combination therapy that included interferon beta-1b, lopinavir–ritonavir and ribavirin, has shown the combination is safe and effective at reducing the duration of viral shedding than lopinavir–ritonavir alone in patients with mild to moderate illness.
These early but important findings, published in The Lancet, do not include severe cases of COVID-19, and the authors stress the need for larger phase 3 trials to examine the effectiveness of this triple combination in critically ill patients.
Experience with influenza suggests that treating hospitalised patients with a combination of multiple antiviral drugs may be more effective than single drug treatments, and minimise the risk of antiviral resistance. The authors hypothesised that this could be a possible therapeutic approach for COVID-19, in which the viral load also peaks around the time of symptom onset.
Professor Kwok-Yung Yuen, from the University of Hong Kong who led the research, said: “Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to health-care workers by reducing the duration and quantity of viral shedding (when the virus is detectable and potentially transmissible). Furthermore, the treatment combination appeared safe and well tolerated by patients.
“Despite these encouraging findings, we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate).”
Secondary outcomes in the new study suggest that clinical improvement and length of hospital stay may be significantly shorter in people treated with triple combination less than seven days after showing symptoms, compared to lopinavir-ritonavir alone.
Previous research found that a combination of oral lopinavir-ritonavir, which is normally used to treat HIV, and ribavirin, an oral hepatitis C virus drug, significantly reduced respiratory failure and death in patients hospitalised with severe acute respiratory syndrome (SARS) during the 2003 outbreak. Interferon beta-1b, which was developed to treat multiple sclerosis (MS), has been shown to reduce viral load and improve lung problems in animal studies of Middle East respiratory syndrome (MERS) coronavirus infection.
In the trial, all patients received standard care including ventilation support, dialysis support, antibiotics, and corticosteroids. The average number of days from symptom onset to start of study treatment was five days.
Treatment with the triple drug combination effectively suppressed viral load (with no detectable virus) within an average seven days of starting treatment, which was significantly shorter than the average 12 days in the control group, treated with lopinavir–ritonavir alone.
Secondary outcomes supported the findings, indicating that clinical improvement was significantly better in the triple combination group, with the triple therapy halving the time to complete alleviation of symptoms.
Co-author Dr Jenny Lo from Ruttonjee Hospital in Hong Kong said: “These findings suggest that interferon beta 1-b may be a key component of the combination treatment and is worth further investigation for the treatment of COVID-19.
“Interferons are naturally occurring proteins, produced in response to viral infection, and the hope is that interferon beta-1b will boost the body’s ability to fight SARS-CoV-2. Future phase 3 trials will soon confirm or refute the usefulness of this candidate drug as a backbone treatment for COVID-19.”
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