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Infectious Disease Virologist: “Nobody Should be Scared of Paxlovid Rebound”

The benefits outweigh the possible rebound of symptoms, according to an investigator who studied the antiviral.


Some people with COVID-19 taking Paxlovid (nirmatrelvir/ritonavir, NM/R) have been experiencing a “rebound” of symptoms and testing positive for COVID-19 after a regimen of the antiviral. President Joe Biden was recently diagnosed with COVID-19, was treated with Paxlovid, and had the “Paxlovid rebound” phenomenon. He has had to quarantine for a few extra days until symptoms subside and he tests negative.

Davey Smith, MD, MAS, head, Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, and a team of investigators studied Paxlovid in a small study published in Clinical Infectious Diseases looking at the Paxlovid rebound and if resistance was taking place.

“This study found that neither development of NM resistance or absence of neutralizing antibody were likely causes of the recrudescence,” the investigators wrote in their study.

Although they were not able to measure treatment levels and T cell responses, Smith et al felt the most likely possibility for the observed recrudescence was insufficient drug exposure.

In thinking about strategies to avoid the recrudescence, one potential idea has been to consider changing the dosing schedule from 5 to 10 days.

“I think we should do studies on that particular option,” Smith stated. “The original study was great. It showed for 5 days of Paxlovid, it prevented people from having to go to the hospital or dying by over 80%. That was amazing compared to those who got placebo. So we know that 5 days works to do what we want it to do in terms of decreasing disease severity.”

He also points out that in that study people did rebound but it "did not greatly increase the need for hospitalization or having people die.”

He says studies looking at a 10 day regimen are important to identify the benefits and risks. Smith is candid in saying they are not sure why this phenomenon is happening, but believes the clinical benefits far outweigh the potential recrudescence.

“Nobody should be scared of a Paxlovid rebound for prescribing this medication," Smith said.

Contagion spoke to Smith about his study, the efficacy of Paxlovid, and why clinicians should consider prescribing the antiviral.