The first clinical trial conducted to prove the effect of anti-HIV drugs- -lopinavir and ritonavir combination- -for treating severe COVID-19 produced negative results. The results of the trial published in The New England Journal of Medicine today said that no benefit was observed with lopinavir–ritonavir treatment in hospitalized adult patients with severe Covid-19, beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit, the report added.
The trial was supported by Major Projects of National Science and Technology on New Drug Creation and Development and others including the Chinese Academy of Medical Sciences (CAMS) Emergency Project of Covid-19 and a National Science Grant for Distinguished Young Scholars.
The authors of The NEJM report stated that they conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. “Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first,” they said in the report.
A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization in the trial. Ninety nine patients were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). But, mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.
The trial concluded that in hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may or may not help to confirm or exclude the possibility of a treatment using these drugs, the study report said.