{"id":10417,"date":"2022-04-25T11:29:21","date_gmt":"2022-04-25T15:29:21","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10417"},"modified":"2022-05-23T15:04:02","modified_gmt":"2022-05-23T19:04:02","slug":"yes-relapses-after-paxlovid-happen-now-what","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/yes-relapses-after-paxlovid-happen-now-what\/2022\/04\/25\/","title":{"rendered":"Yes, Relapses After Paxlovid Happen — Now What?"},"content":{"rendered":"
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Young Monk in the Greek Style, from Mascarade \u00e0 la Greque, Alexandre Petitot (1727-1801).<\/p><\/div>\n

Around two weeks ago, one of my long-term, very stable patients with HIV called me saying she’d just been diagnosed with COVID-19. Over 60 with hypertension, and overweight, she qualified for nirmatrelvir\/r (Paxlovid) under the Emergency Use Authorization (EUA), and took it without problem.<\/p>\n

(Certain details changed for confidentiality.)<\/p>\n

In fact, she started to improve within 24 hours of the first dose. Complained a bit about the metallic taste, but was thrilled at this rapid recovery.<\/p>\n

She then contacted me again a week later, saying she’d relapsed. More nasal congestion, cough, and fatigue — not as bad as when the illness started, but unmistakably a relapse. Not only that, the home antigen test, which started out as a dark line at the outset, became a barely discernible line after the treatment, and now was clearly positive again.<\/p>\n

Her biggest concern was getting back out in the world without infecting someone. She really wasn’t that sick; she just wanted advice about when she could return to work and start socializing again.<\/p>\n

“Avoid close contact with others until that test clears,” I said. (Which it did a few days later, and she completely recovered.) But certainly the whole thing was a head-scratcher for both of us.<\/p>\n

Turns out these relapses do occur; this was just the first time I saw it. The investigators from Pfizer observed them in their clinical trial EPIC-HR, and reported it to the FDA. Take a look at this figure from their study, which was not included in the NEJM<\/em> paper<\/a>, but did appear in an FDA report:<\/a><\/p>\n

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See those lines heading upwards from day 10-14? Those are relapses. Sequencing of SARS-CoV-2 from these cases did not demonstrate resistance mutations either at baseline or at relapse that correlated with resistance. Specifically:<\/p>\n

In summary, currently there are no clear signals of baseline or treatment-emergent NIR resistance from the preliminary analyses of clinical trial EPIC-HR. These analyses will continue to be conducted as more complete data from EPIC-HR are obtained and reported.<\/p><\/blockquote>\n

A detailed analysis of a similar relapsing case is available as a pre-print<\/a> — viral sequence the same at 3 time points (no resistance or reinfection), respiratory multiplex PCR negative (no new pathogen), good antibody response.<\/p>\n

Not surprisingly, as use of Paxlovid increases along with the supply, the anecdotal reports of these relapses increase in parallel. Not just in clinical practice — they’ve popped up on social media<\/a> and in the press<\/a>. It’s now become a standard part of my counseling to people, that this return of symptoms and test positivity might happen.<\/p>\n

So we know that relapses happen. What don’t<\/em> we know about these cases? Quite a bit, actually.<\/p>\n