No benefit of Lopinavir–Ritonavir combo in severe COVID-19, says NEJM

China: With the rising cases of Coronavirus acrsoos the country, and no definite treatment that works on the disease, doctors have been experimenting with HIV combination drugs Lopinavir–Ritonavir on Covid-19 seriously ill patients.

Recently, Doctors at SMS Hospital took the decision of trying out the medicine on an Italian man and his wife who had developed severe respiratory problems following which a decision was taken to put them on the combination of lopinavir and ritonavir. 

Read Also : SMS Hospital Gives Anti-HIV Drugs To Coronavirus-Affected Elderly Italian Couple

As the couple's condition improved, a recent protocol by ICMR researchers was also published in the IJMR for the use of such drug restricted public health emergency use.

Read Also : HIV Drugs In Coronavirus Patients: ICMR Scientists Release Protocol For Restricted Public Health Emergency Use

However, this has given rise to a much-sparked debate, whether the improvement was one odd change or that the combination really works

In the view of sorting this issue, Cao and colleagues performed a randomized clinical trial to find the efficacy of lopinavir-ritonavir in patients with Covid-19 in Wuhan, China which does not seem to be in favor of the drugs.The results, which have been published in the NEJM clearly states 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 help to confirm or exclude the possibility of a treatment benefit, the researchers stated

Lopinavir acts against the viral 3CL protease have modest antiviral activity and ritonavir increases its plasma half-life through the inhibition of cytochrome P450.

On January 18, the first patient was enrolled in this open-label trial, about a week after SARS-CoV-2 had been identified and sequenced. The investigators recruited patients who 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 and who were receiving a range of ventilatory support modes, from nothing to mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Enrollment was stratified according to the severity of illness as indicated by the level of ventilatory support administered.

All the patients received standard care, and half were randomly assigned to receive lopinavir-ritonavir for 14 days. The primary endpoint was the time to clinical improvement, defined as the time from randomization to either discharge from the hospital or improvement on a multifactorial set of prespecified criteria, whichever came first. The trial aimed to enroll 160 patients.

Unfortunately, the trial results were disappointing. No benefit was observed in the primary endpoint of time to clinical improvement: both groups required a median of 16 days. But the results for certain secondary endpoints are intriguing. A slightly lower number of deaths was seen in the lopinavir-ritonavir group, although this observation is difficult to interpret, given the small numbers and the fact that the standard-care group appears to have been sicker at baseline.

Lopinavir-ritonavir lesser effectivity may be due to two major factors.

1)First, the authors chose a particularly challenging population. The patients recruited for the study were late in infection and already had considerable tissue damage (as evidenced by compromised lung function and 25% mortality in the control group).

2)Second, lopinavir simply isn't particularly potent against SARS-CoV-2. The concentration necessary to inhibit viral replication is relatively high as compared with the serum levels found in patients treated with lopinavir-ritonavir.Very little information about drug concentrations in the tissues where SARS-CoV-2 is replicating is available currently.

Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit, concluded the authors.

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DOI: 10.1056/NEJMoa2001282