Triple antiviral combo shows early promise: Study

A two-week course of antiviral therapy with interferon beta-1b plus lopinavir–ritonavir and ribavirin, started within seven days of onset of coronavirus symptoms, is safe and more effective at reducing the duration of viral shedding than lopinavir–ritonavir alone in patients with mild to moderate illness, according to the first randomised trial of this triple combination therapy involving 127 adults (18 years and older) from six public hospitals in Hong Kong. The subjects did not include severe cases of coronavirus.

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The study suggests 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. “The treatment combination appeared safe and well tolerated by patients,” said Professor Kwok-Yung Yuen from the University of Hong Kong, who led the research.

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Experience with influenza, which has a high viral load (how much virus is present in an infected person’s body) around the time symptoms appear, 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 to coronavirus, in which the viral load also peaks around the time of symptom onset.

“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). 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),” he said in the Lancet.

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Previous research found that a combination of oral lopinavir-ritonavir (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.

The open label study enrolled 127 adults (average age 52 years) admitted to one of six public hospitals with laboratory-confirmed SARS-CoV-2 infection between February 10 and March 20 — in Hong Kong, everyone who tests positive for COVID-19 is admitted to hospital.

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) in the nasopharyngeal swab 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.

“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,” said co-author Dr Jenny Lo from Ruttonjee Hospital in Hong Kong. “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.”