Triple antiviral drug combo shows promise for treating COVID-19

A two-week course of antiviral therapy that combines the power of three drugs has shown promise in treating hospitalised patients with mild to moderate COVID-19 in a carefully undertaken phase 2 clinical trial.

The results of the trial, published in the journal The Lancet, involved 127 adults from six public hospitals in Hong Kong.

The drug combination tested in the trial included -- interferon beta-1b which was developed to treat multiple sclerosis (MS), lopinavir-ritonavir which is normally used to treat HIV and ribavirin, an oral hepatitis C virus drug.

The findings of the phase 2 trial provided evidence that early treatment with triple antiviral therapy alongside standard care is safe and shortens duration of viral shedding (when the virus is detectable and potentially transmissible) compared to lopinavir-ritonavir alone -- average 7 days vs 12 days -- in patients with mild to moderate COVID-19.

People in the triple combination group spent 5.5 days less in hospital on average compared to those in the control group who received the lopinavir-ritonavir treatment alone.

"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," said Professor Kwok-Yung Yuen from the University of Hong Kong who led the research.

"Furthermore, the treatment combination appeared safe and well tolerated by patients," Yuen said.

Previous research found that a combination of oral lopinavir-ritonavir and ribavirin significantly reduced respiratory failure and death in patients hospitalised with severe acute respiratory syndrome (SARS) during the 2003 outbreak.

Interferon beta-1b has been shown to reduce viral load and improve lung problems in animal studies of Middle East respiratory syndrome (MERS) coronavirus infection.

The new study involving COVID-19 patients enrolled 127 adults admitted to one of six public hospitals with laboratory-confirmed SARS-CoV-2 (the virus responsible for COVID-19) infection between February 10 and March 20 of this year.

Participants were randomly assigned to 14 days of either the triple combination of oral lopinavir-ritonavir (400mg/100mg) and ribavirin (400mg) every 12 hours, plus up to three doses of injectable interferon beta-1b (8 million international units) on alternate days for patients admitted to hospital less than seven days from symptom onset (86 patients; combination group); or lopinavir-ritonavir alone every 12 hours (41 patients; control group).

In the trial, all patients received standard care including ventilation support, dialysis support, antibiotics, and corticosteroids.

Treatment with the triple drug combination effectively suppressed viral load (with no detectable virus) in the nasopharyngeal swab within an average 7 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 (average 4 days vs 8 days) and resulting in significantly shorter average hospital stay (9 days vs 14.5 days).

"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 study co-author 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." [1] There was no difference in adverse events between the treatment groups, and none of the side effects in the combination group were severe.

No patients died during the study.

However, the researchers stressed the need for larger phase 3 trials to examine the effectiveness of this triple combination in critically ill patients.