Approved HIV treatment offers no benefit for adults with COVID-19
Treatment with lopinavir-ritonavir, a combination treatment for HIV, did not significantly advance the time to clinical improvement, decrease mortality or lower the detectable level of throat viral RNA among patients with serious cases of COVID-19, according to data from a recent study in The New England Journal of Medicine.
“Beginning in December 2019, a novel coronavirus, designated SARS-CoV-2, has caused an international outbreak of respiratory illness termed COVID-19,” Bin Cao, MD, of the Department of Pulmonary and Critical Care Medicine and the Center of Respiratory Medicine at the National Clinical Research Center for Respiratory Diseases and the China-Japan Friendship Hospital, and the Institute of Respiratory Medicine at the Chinese Academy of Medical Sciences, and colleagues wrote. “The full spectrum of COVID-19 ranges from mild, self-limiting respiratory tract illness to severe progressive pneumonia, multiorgan failure and death. Thus far, there are no specific therapeutic agents for coronavirus infections.”
Cao and colleagues performed a randomized, controlled, open-label trial among hospitalized adult patients with confirmed COVID-19 infection to test the efficacy and safety of lopinavir-ritonavir in addition to standard care compared with standard care alone. According to the study, 199 patients were randomly assigned in a 1:1 ratio to either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice per day for 14 days plus standard care (n = 99) or standard care alone (n = 100).
Overall, researchers found that treatment with lopinavir-ritonavir did not correlate with a difference from standard care in time to clinical improvement (HR = 1.24; 95% CI, 0.9-1.72). Through a modified intention-to-treat analysis, researchers found that lopinavir-ritonavir resulted in a median time to clinical improvement that was decreased by 1 day than that seen with standard care (HR = 1.39; 95% CI, 1-1.91). The study also showed that 28-day mortality was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25%; 95% CI, 17.3 to 5.7).
Gastrointestinal adverse events were more frequent in the lopinavir-ritonavir group. While 13 patients stopped treatment with lopinavir-ritonavir due to adverse events, serious adverse events were more common in the standard-care group.
“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,” the authors concluded. “These early data should inform future studies to assess this and other medication in the treatment of infection with SARS-CoV-2. Whether combining lopinavir-ritonavir with other antiviral agents, as has been done in SARS and is being studied in MERS-CoV, might enhance antiviral effects and improve clinical outcomes remains to be determined.”
In an accompanying commentary, Lindsey R. Baden, MD, associate professor of medicine at Harvard Medical School, and Eric J. Rubin, MD, PhD, Irene Heinz Given Professor of Immunology and Infectious Diseases at Harvard’s T.H. Chan School of Public Health, said that completing this study was “a heroic effort” and stressed that, despite the lack of efficacy, there are many “important takeaways” from the study.
“The investigators appropriately prioritized speed, designing a trial that could rapidly produce an answer,” Baden and Rubin wrote. “What we’ve learned from their work can help inform the design of new trials.”
The authors added that randomized clinical trials that are started quickly and of high quality are possible in epidemic conditions, even in “the trying circumstances” that existed in Wuhan.
“The results of such trials, providing either convincing positive or convincing negative findings, will be central to clinical care as the dangerous coronavirus outbreak continues,” Baden and Rubin wrote. – by Caitlyn Stulpin
Disclosures: Cao and Rubin reports no relevant financial disclosures. Baden reports receiving grants from the Gates Foundation, the NIH/NIAID and the Ragon Institute for HIV vaccine development outside the submitted work.