Lopinavir-Ritonavir Shows No Substantial Benefit for Patients with COVID-19

March 25, 2020

A study investigated the use of lopinavir-ritonavir for the potential treatment of hospitalized patients with severe COVID-19.

Lopinavir-ritonavir treatment showed no benefit in hospitalized adult patients with severe COVID-10, according to results from a clinical study published in the New England Journal of Medicine.

There are no specific therapeutic agents for coronavirus infection. However, after the emergence of severe acute respirator syndrome (SARS) in 2003, lopinavir was identified as having in vitro inhibitory activity against SARS-CoV, the virus that causes SARS. Lopinavir is a HIV type 1 aspartate protease inhibitor. Ritonavir combined with lopinavir increases its plasma half-life through the inhibition of cytochrome P450, according to the study.

The study included a total of 199 patients with laboratory-confirmed SARS-CoV-2 infection who were hospitalized. Patients had an oxygen saturation of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of less than 300 mm Hg. For the trial, patients received either lopinavir-ritonavir (400 mg or 100 mg, respectively) twice per day for 14 days, in addition to standard care, or standard care alone.

Overall, treatment with lopinavir-ritonavir was not associated with a difference from standard of care in time to clinical improvement (hazard ratio for clinical improvement, 1.24; 9% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% versus 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7), according to the study. Additionally, the percentages of patients with detectable viral RNA at various time points were similar.

The study results determined that lopinavir-ritonavir treatment added to standard supportive care was not associated with clinical improvement or mortality in seriously ill patients with COVID-19 compared with standard care alone.

“However, in the modified intention-to-treat analysis, which excluded 3 patients with early death, the between-group difference in the median time to clinical improvement (median, 15 days vs 16 days) was significant, albeit modest,” the researchers wrote.

Additionally, the overall mortality in the trial (22%) was substantially higher than the 11% to 14.5% mortality reported in initial descriptive studies of hospitalized patients with COVID-19, which indicates the enrollment of a severely ill population, they noted.

“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,” the researchers concluded.

References:

1. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. New England Journal of Medicine. 2020. Doi: 10.1056/NEJMoa2001282