By Jennifer Kearney-Strouse
The decision to prescribe nirmatrelvir/ritonavir (Paxlovid) shouldn't be based on symptoms, said Carlos del Rio, MD, FACP, at a Friday morning session.
"I frequently hear somebody say, 'Well, you know, I'm 75 years old, I got infected with COVID. But my doctor doesn't want to prescribe it because I have mild symptoms,'" Dr. del Rio said. "It's not the severity of symptoms that determines whether you need to be treated or not. It's your risk of progression to severe disease."
Dr. del Rio discussed this and other guidance on the drug during his talk, "COVID-19 Update 2023: Where Are We Now?"
Nirmatrelvir/ritonavir is authorized for patients with mild to moderate COVID-19 who are at high risk for disease progression, he explained, and it must be started within five days of symptom onset. The dose should be reduced in those with moderate renal insufficiency, and the drug is not recommended for patients with severe renal insufficiency or severe hepatic impairment, Dr. del Rio said.
The hardest part of prescribing the drug is the long list of interactions with ritonavir, said Dr. del Rio, who is a distinguished professor of medicine and executive associate dean for Emory at Grady in Decatur, Ga., and president of the Infectious Diseases Society of America.
Some medicines should not be coadministered, such as amiodarone, clopidogrel, rifampin, and rivaroxaban, while with others, such as calcineurin inhibitors, the drug may need to be paused or the dose markedly reduced. Statins, meanwhile, can usually just be stopped temporarily, Dr. del Rio said.
"In general, again, I hear frequently people say 'Well, my doctor said I shouldn't take [Paxlovid] with some medications I'm taking.' Ninety-nine percent of the time that medication is a statin, and there's very few people that cannot stop statins," he said.
For guidance, he recommended COVID-19 treatment guidelines from the NIH and IDSA and the University of Liverpool's COVID‐19 drug interaction checker. The IDSA has also developed a resource for clinicians on managing drug interactions with nirmatrelvir/ritonavir.
Dr. del Rio also addressed the phenomenon of so-called "Paxlovid rebound," in which people test positive for COVID-19, take the medication, test negative, and then eventually test positive again. "I remind people it's not rebound from Paxlovid," he said. "Anybody can have a relapse, even if you don't get treatment."
The EPIC-HR study found that rebound infection after Paxlovid was about 5%, Dr. del Rio said. "If you look at Twitter, it's about 100%," he said, to laughter from the audience. "It's somewhere in the middle of that."
He pointed to a preprint study in which Paxlovid-eligible patients with COVID-19 who took the drug were compared with those who opted not to. Both groups tested regularly at home and answered surveys about symptoms. Viral rebound occurred in 14% of people who took Paxlovid versus 9% of those who did not, while symptomatic rebound was 18% versus 7%. Five percent of those who took the drug remained consistently positive versus 0% of those who did not, and the time from symptom start to negative test result was 6.4 days versus 6.1.
"There's really not a difference here," Dr. del Rio said. "Basically, yes, you probably have a little bit more rebound in people that get treated with Paxlovid, but it's not a Paxlovid phenomenon."
Dr. del Rio stressed that nirmatrelvir/ritonavir is not reaching the patient population that is most likely to benefit from it. Data published by The Economist in July 2022 found that although 2.4 million doses of Paxlovid had been administered in the U.S., mortality and hospitalizations had not decreased. A likely reason is that the counties in which the drug was most heavily prescribed were also the ones that had the highest vaccination rates and the lowest rates of comorbidity, he explained.
"The places where you are not getting a lot of Paxlovid are also places where you didn't get a lot of the population vaccinated, and you had higher comorbidities. Not surprisingly, you still continue to see mortality," he said. "So we're not getting the drug to the people that need it the most, and I think that's really a challenge that we still have ahead." ■