November 13, 2023
2 min read
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on .
” data-action=subscribe>
Subscribe
We were unable to process your request. Please try again later. If you continue to have this issue please contact [email protected].
Back to Healio
Key takeaways:
- Half of patients who experienced virologic rebound after taking Paxlovid also reported symptom rebound.
- However, Paxlovid remains a critical treatment option for high-risk patients, researchers said.
About 20% of patients with COVID-19 experienced virologic rebound after receiving Paxlovid, according to an observational study published in Annals of Internal Medicine.
“We conducted this study to address lingering questions about Paxlovid and virologic rebound in COVID-19 treatment,” Mark Siedner, MD, MPH, an associate professor of medicine at Harvard University, said in a press release. “We found that the [virologic rebound (VR)] phenomenon was much more common than expected … and that individuals shed live virus when experiencing a rebound, implying the potential for transmission after initially recovering from the virus.”
Half of patients who experienced virologic rebound after taking Paxlovid also reported symptom rebound. Image Source: Adobe Stock.
There have been prior reports of VR with Paxlovid (nirmatrelvir/ritonavir; Pfizer), including in former CDC Director Rochelle P. Walensky, MD, and President Joe Biden.
However, previous research has suggested that viral RNA rebound and symptom rebound occurred at similar frequencies in patients who received nirmatrelvir/ritonavir and placebo.
For the current study, Siedner and colleagues compared VR outcomes of adults with acute COVID-19 who received a 5-day regimen of nirmatrelvir/ritonavir (n = 72) and those who did not receive treatment (n = 55).
Compared with untreated participants, those taking nirmatrelvir/ritonavir tended to be older, were vaccinated against COVID-19 and were more likely to be immunosuppressed.
The researchers found that 20.8% of participants who received nirmatrelvir/ritonavir had VR vs. 1.8% of participants left untreated, yielding an absolute difference of 19 percentage points (95% CI, 9-29).
In multivariable models that included demographics and other clinical characteristics, only nirmatrelvir/ritonavir use was linked to VR (adjusted OR = 10.02; 95% CI, 1.13-88.74).
VR was more common among participants who started therapy within 2 days of symptom onset (26.3%) compared with those who started 2 or more days after symptom onset (0%).
Additionally, 50% (95% CI, 25-75) of participants with VR also reported symptom rebound, whereas two were completely asymptomatic.
Although VR was more frequent than expected, “Paxlovid remains a lifesaving drug I prescribe to high-risk patients,” Johnathon Li, MD, a resident physician at the University of Pittsburgh, said in the release.
“This study, while informative, does not change the fact that this drug is very effective at preventing hospitalizations and death,” Li said. “Instead, it offers valuable insights to Paxlovid patients, helping them understand what to expect and how long they might be contagious.”
In a related editorial, Myron S. Cohen, MD, a Yeargan-Bate Professor of Medicine, Microbiology and Epidemiology at the University of North Carolina School of Medicine, and Elizabeth R. Brown, ScD, a professor of biostatistics, bioinformatics and epidemiology at the Fred Hutch Cancer Center, noted that patients who received nirmatrelvir/ritonavir in the study “likely had clinical benefit, and it is important to note that rebound was not observed in most treated participants.”
Still, “further consideration of the dosage, timing, and duration of treatment with [nirmatrelvir/ritonavir] is essential to inform optimal use of this drug,” Cohen and Brown wrote.
References:
Sources/Disclosures
Collapse
Disclosures:
Brown reports receiving support from the National Institute of Allergy and Infectious Diseases (NIAID) and grants from the Bill & Melinda Gates Foundation, National Cancer Institute and NIAID. Cohen reports receiving support from the NIH and consulting fees from Aerium, AstraZenica and Atea. Edelstein reports no relevant financial disclosures. Li reports receiving a grant from Merck.
Perspective
Back to Top
Amesh A. Adalja, MD
The study, which is limited by its observational nature, provides more evidence that there is likely a real correlation between Paxlovid use and viral rebound, although the causal process is still unknown. It remains unclear why the majority of Paxlovid users don’t have rebound and a minority do. The clinical implications of rebound have to be tempered by the fact that the chief purpose of the drug is to prevent severe disease — which it does irrespective of rebound. Rebound should not dissuade anyone from using this lifesaving medication. However, it is nonetheless important to understand the causal factors surrounding rebound and whether the phenomenon can be minimized with altered dosing or longer half-life SARS-CoV-2 protease inhibitors such as ensitrelvir (Shionogi) (available in Japan).
Amesh A. Adalja, MD
Senior scholar
Johns Hopkins Center for Health Security
Disclosures: Adalja reports no relevant financial disclosures.
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on .
” data-action=subscribe>
Subscribe
We were unable to process your request. Please try again later. If you continue to have this issue please contact [email protected].
Back to Healio
