Despite its promising potential, a combination drug therapy commonly used to treat HIV does not appear to be an effective treatment against COVID-19, the severe illness caused by SARS-CoV-2.
The novel coronavirus began in December 2019 and has resulted in an international outbreak of respiratory illness in the months since. Symptoms range from mild illness to severe pneumonia, multi-organ failure, and death. As of March 19, there are more than 209,000 confirmed global cases and over 8,700 deaths, according to a situation report published by the World Health Organization. It took over three months to reach the first 100,000 confirmed cases and only 12 days to reach the next 100,000, the report adds.
“Unfortunately, the trial results were disappointing,” wrote researchers in an accompanying editorial. So far, there are no specific treatments or cures for coronavirus infections.
To determine whether lopinavir-ritonavir, a combination treatment used to control HIV infection, might play a role in the treatment of COVID-19, researchers randomly assigned 99 of 199 hospitalized adult patients with confirmed coronavirus infection and difficulty breathing. Lopinavir-ritonavir decreases the amount of human immunodeficiency virus in the body so that the immune system can better combat the disease. Patients were given (400 mg and 100 mg, respectively) twice a day for 14 days in addition to standard care. Their health outcomes were compared with the 100 patients who did not receive the drug.
Generally speaking, there was no significant difference in those who took the drug versus those who received standardized care. On average, both groups required around 16 days of medical treatment, though those who had been given the drug showed improvements about a day earlier.
“In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care,” write the researchers in the New England Journal of Medicine. “We found that lopinavir-ritonavir treatment did not significantly accelerate clinical improvement, reduce mortality, or diminish throat viral RNA detectability in patients with serious Covid-19."
However, a slightly lower number of deaths was seen in the lopinavir-ritonavir group, though it is difficult to interpret the results given the small scale of the study.
“Of note, the overall mortality in this trial was substantially higher than the 11 percent to 14.5 percent mortality reported in initial descriptive studies of hospitalized patients with Covid-19, which indicates that we enrolled a severely ill population,” write the scientists.
The researchers add that the number of patients who had received lopinavir-ritonavir with serious complications like secondary infections or required breathing assistance for respiratory failure were fewer than those who had not received the treatment, so further research is needed to determine whether the drug may be given at a certain stage to reduce complications in COVID-19. There were other limitations with the study, such as a lack of a double-blind trial, which means it's possible knowing who was being treated could have influenced clinical decision-making.
Why wasn’t lopinavir-ritonavir effective? It could be due to the circumstances of the study. For example, the medical team targeted patients late in infection, some of whom already had considerable tissue damage. The researchers conclude that future trials in patients with severe illness may help to “confirm or exclude the possibility of a treatment benefit.”