When President Joe Biden tested positive for Covid-19 on July 21, his doctor advised him to take the antiviral drug paxlovide. The drug significantly reduces the likelihood of hospitalization or death in someone at high risk of developing severe Covid. Biden began a five-day course that day, and within six days he tested negative for the virus and was cleared to leave isolation, according to the White House.
Biden’s chief medical adviser. Anthony Fauci also took paxlovide when he contracted Covid in June but soon tested positive for the disease again. So he took a second round of the drug even though it wasn’t approved.
Since paxlovid became available seven months ago, it has overtaken other available therapies designed to prevent life-threatening Covid symptoms in high-risk patients. Some doctors are quick to prescribe it, but much about the Covid pandemic is controversial. Some patients worry about the possible return of the disease, while others have difficulty convincing their doctors that they are good candidates for the drug.
“Paxolid is still a viable drug,” says Dr. Priya Nori, an infectious disease physician at Montefiore Health System, although it may not be right for everyone.
In a clinical trial, people who had mild to moderate Covid and were at high risk of becoming seriously ill had an 88% lower risk of being hospitalized or dying from the disease if they took paxlovide within five days of symptoms.
But even as infectious disease experts praise the treatment’s effectiveness, many doctors say they have questions about prescribing the drug and want better data.
Here are answers to some common questions about Paxlovid.
Q: What is Paxlovid and how does it work?
Paxlovide is an antiviral drug made up of two drugs: one blocks a key enzyme needed to replicate the Covid virus, and the second blocks the metabolism of the first drug in the liver so it doesn’t leave the body as quickly. Patients take three pills twice a day for five days.
Q: Who should take Paxlovide?
When the FDA approved the emergency use of paxlovide, it specified that the drug be prescribed to people at high risk of becoming seriously ill from Covid. The high-risk list is long, including people over 65 and those with chronic or serious health conditions such as cancer, obesity, diabetes, asthma and heart disease.
Seven months after paxlovide was approved, some patients still have the protection of two booster shots of a Covid vaccine, and many were previously infected with the Omicron variant of the virus. So doctors are left to evaluate how much a patient’s history increases or decreases their risk of serious infection, balancing the utility of prescribing a drug that also has downsides.
Some people who fall into the high-risk category cannot take paxlovide if they take any of the long list of drugs that can interact with antivirals. Temporarily stopping certain medications on the list — such as those used to treat high cholesterol or high blood pressure — until a course of paxlovide is completed may not pose a risk of serious health problems. But in people taking medications such as transplant rejection drugs or antiarrhythmic drugs that control their heart rate, “these can cause catastrophic complications” when taken with paxlovide, said Dr. Scott Roberts says.
Paxlovide is not recommended for people who are unlikely to become seriously ill from Covid. In June, the drug’s maker, Pfizer, announced it was stopping a clinical trial for standard-risk people because paxlovide did not significantly reduce hospitalizations and deaths in that group. The trial included both vaccinated and unvaccinated subjects.
Perhaps these results are not surprising, since “for people who are at low risk, the risk of hospitalization is so low that taking paxlovide is not adding any benefit,” said infectious disease chief Dr. Daniel Kuritzkes at Brigham and Women’s Hospital in Boston.
Also in June, Pfizer announced that it had applied to the FDA for full approval of Paxlovid.
Q: What are the alternatives for people who cannot take Paxlovide?
Several other antiviral drugs (Vecluri and Legevrio) and a monoclonal antibody drug (bebtelovimab) also reduce the risk of hospitalization and death from Covid. But they are less convenient, require injections or infusions, or are not as effective as paxlovide. However, they are likely if one cannot take Paxlovide.
Q: How often do people experience rebound infections after taking Paxlovide?
A small number of people get Covid symptoms after finishing a five-day course of Paxlovide and test positive for the coronavirus again. But there is much debate about how many patients are affected and why rebound occurs.
In Pfizer clinical trials, 1% to 2% of participants tested positive for Covid again after completing a course of paxlovide. Because rebound occurred in both those who received the drug and those who received placebo, the FDA concluded that “it is unclear whether this is related to drug treatment.”
A study published in June by Mayo Clinic researchers found that less than 1% of 483 high-risk patients who received paxlovide experienced rebound symptoms.
Anecdotal reports suggest that the rebound figure is higher though. Several prominent people in the medical community have reported experiencing rebound infections and symptoms, although they are usually mild. In addition to Fauci, director of the National Institute of Allergy and Infectious Diseases, Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University and Dr. Peter HotzDean of the National School of Tropical Medicine at Baylor College of Medicine.
“I’m still confused about it, and most of the people I talk to about it are still confused, because we don’t know exactly why it’s happening,” said Dr. Robert Wachter, a professor and department chair of medicine at the University of California-San Francisco. In May, Wachter Tweeted about his wife’s rebound experience, author Katie Hafner. “Public data on frequency doesn’t sync with everyone’s experience.”
There are several theories as to why rebound occurs. Some experts suspect that the drug does not completely eradicate the virus in some people with high viral loads, leading to relapses after a five-day course. Others suggest that because treatment is started as soon as Covid symptoms appear, the body’s immune system doesn’t get a chance to get a good look at the virus and ramps up to fight it once treatment ends. Or it could be that some people clear antiviral drugs from their bodies faster than others.
“If you have rapid clearance, you may not have the exposure necessary to clear the virus,” says Ashley Brown, a virologist at the University of Florida in Orlando.
“We continue to monitor the data, but to date we have not seen the emergence of resistance in paxlovide-treated patients and believe that the return of elevated nasal viral RNA is uncommon and not uniquely associated with treatment,” Pfizer spokesman Keith Longley said in an email.
Q: Given the rebound effect, do current prescribing guidelines need to be revised?
Some medical experts think that changing the timing or duration of a course of paxlovide may eliminate the rebound effect some patients experience. If people start taking paxlovide on day 3 of symptoms, for example, their body’s defenses may be boosted, boosted by vaccines or previous infections, Norrie said.
“Then we boost with antivirals, and this rebound can be mitigated,” he said.
Many experts believe a five-day course is too short, says Wachter, who wants more data. “You would think that doing a study in five days versus seven days versus 10 days wouldn’t be that difficult,” he said.
According to Pfizer’s Longley: “There may be some patient populations who may benefit from longer treatment or repeated treatments, and we are considering additional studies to evaluate this in some populations.”
Q: Fauci took a second course of paxlovid after experiencing a rebound effect. Can other patients do it?
Fauci said she took a second course of paxlovid after she tested positive for Covid and felt sicker with a second round with the virus.
Prescription guidelines clearly state that “Paxovid is not approved for use for more than five consecutive days.”
Not all physicians agree with the guidelines. “For people who are really high-risk, it’s hard to say, ‘Just take Tylenol,'” said Dr. David Wohl, professor of medicine in the department of infectious diseases at the University of North Carolina-Chapel Hill.
At Brigham and Women’s Hospital, physicians generally do not recommend a second course of paxlovide for patients who experience a rebound, Kuritzkes said, “although there is some variation in opinion.”
In an FDA directive to providers in May, the director of the Office of Infectious Diseases said. John Farley says, “At this time there is no evidence of benefit for longer courses of treatment (eg, 10 days versus 5 days). recommended in the provider fact sheet for paxlovide) or repeating a course of treatment with paxlovide in patients with recurrent COVID-19 symptoms after completion of the treatment course.”
Fauci’s move was disturbing to some physicians.
“I was a little surprised and surprised that the top doctor in the country went against the guidance,” said Yale’s Roberts. “It sends a mixed message to me. I imagine I’ll get patients who say, ‘Dr. Fauci got two courses. Why not me?'”
Q: Are people contagious if they have a rebound? What should separate them?
If people test positive again after a course of paxlovide, Kuritzkes said, it’s assumed they’re contagious, and they should be isolated from others.
Q: Will the coronavirus become resistant to Paxlovide?
That’s a concern, experts say, but there’s no evidence yet that it’s happened.
“The virus is always mutating in all regions of its genome, so at some point paxlovide will probably be less effective than it was in the study a year ago,” Roberts said.
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