{"id":10411,"date":"2022-04-12T12:56:06","date_gmt":"2022-04-12T16:56:06","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=10411"},"modified":"2022-04-12T14:14:23","modified_gmt":"2022-04-12T18:14:23","slug":"should-we-prescribe-nirmatrelvir-r-paxlovid-to-low-risk-covid-19-patients","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/should-we-prescribe-nirmatrelvir-r-paxlovid-to-low-risk-covid-19-patients\/2022\/04\/12\/","title":{"rendered":"Should We Prescribe Nirmatrelvir\/r (Paxlovid) to Low-Risk COVID-19 Patients?"},"content":{"rendered":"<div id=\"attachment_10414\" style=\"width: 236px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-10414\" class=\"wp-image-10414\" src=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-11.05.57-AM.png\" alt=\"\" width=\"226\" height=\"336\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-11.05.57-AM.png 575w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-11.05.57-AM-202x300.png 202w\" sizes=\"auto, (max-width: 226px) 100vw, 226px\" \/><p id=\"caption-attachment-10414\" class=\"wp-caption-text\">I usually put a clever caption below these vintage public health posters, but can&#8217;t think of one. Happy to take suggestions!<\/p><\/div>\n<p>The top recommended treatment for <em>high-risk<\/em> outpatients with COVID-19 in the <a href=\"https:\/\/www.covid19treatmentguidelines.nih.gov\/management\/clinical-management\/nonhospitalized-adults--therapeutic-management\/?utm_source=site&amp;utm_medium=home&amp;utm_campaign=highlights\" target=\"_blank\" rel=\"noopener\">NIH Guidelines<\/a> is nirmatrelvir\/r (Paxlovid). It&#8217;s quite clear why.<\/p>\n<p>In the <a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2118542\" target=\"_blank\" rel=\"noopener\">EPIC-HR study<\/a>, unvaccinated people at high risk for severe outcomes had an 89% reduction in the risk for hospitalization or death compared to placebo. If we just look at mortality &#8212; another important endpoint, don&#8217;t you think? &#8212; nirmatrelvir\/r beat out placebo by a score of 0 (nirmatrelvir\/r) to 13 (placebo).<\/p>\n<p>Let&#8217;s add to this very favorable outcome several other benefits:<\/p>\n<ul>\n<li><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMc2119407\" target=\"_blank\" rel=\"noopener\">The reliable activity against all variants<\/a><\/li>\n<li>The relatively good safety profile<\/li>\n<li>The short course of treatment (5 days)<\/li>\n<li>The substantial reduction in viral load, the most of any drug tested to date<\/li>\n<li>That it is pills rather than an IV<\/li>\n<\/ul>\n<p>Yes, folks, we have a winner! Sure, it has lots of drug interactions and it tastes terrible, but it&#8217;s far and away the best choice out there right now.<\/p>\n<p>So if we recommend this treatment for high-risk people with COVID, what about for symptomatic people who are <em>not<\/em> at high risk? Not now, but imagine a time when we had sufficient supply. Should we also recommend it for them?<\/p>\n<p>I thought the answer was straightforward, and will give my views below. But I had an inkling that this wasn&#8217;t so clear a few weeks ago when one of my smart colleagues held the opposite opinion.<\/p>\n<p>To test these choppy waters, I posted this poll online:<\/p>\n<blockquote class=\"twitter-tweet\" data-width=\"500\" data-dnt=\"true\">\n<p lang=\"en\" dir=\"ltr\">Let&#39;s suppose there&#39;s an ample supply of nirmatrelvir\/r (Paxlovid), and you can prescribe it for anyone with symptomatic COVID-19. Cost not an issue. Based on what we know today, would you do so for &quot;low-risk&quot; cases? Why or why not?<\/p>\n<p>&mdash; Paul Sax (@PaulSaxMD) <a href=\"https:\/\/twitter.com\/PaulSaxMD\/status\/1513118888703234056?ref_src=twsrc%5Etfw\">April 10, 2022<\/a><\/p><\/blockquote>\n<p><script async src=\"https:\/\/platform.twitter.com\/widgets.js\" charset=\"utf-8\"><\/script><\/p>\n<p>Wow. Not only is there a pretty even split, but responses are <em>so<\/em> interesting, and quite strongly held. It&#8217;s fascinating to read them.<\/p>\n<p>(And, by the way Dr. Titanji, <a href=\"https:\/\/twitter.com\/Boghuma\/status\/1513127490218246144?s=20&amp;t=NfvkzCCMUp2G3flEea-DBg\" target=\"_blank\" rel=\"noopener\">good call.<\/a>)<\/p>\n<p>My own view? Given sufficient supply &#8212; and we&#8217;re not there yet &#8212; I\u2019d certainly recommend nirmatrelvir\/r even for low-risk symptomatic people.\u00a0The motivation lies in the already summarized favorable results of the high-risk study, and hinted at even in the interim analysis of EPIC-SR, the study in low-risk people.<\/p>\n<p>Remember<em>,<\/em>\u00a0<em>some<\/em> <a href=\"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/fullarticle\/2770542\" target=\"_blank\" rel=\"noopener\">low-risk younger people get severe disease<\/a>. (Here&#8217;s a <a href=\"https:\/\/twitter.com\/AnnalijnConklin\/status\/1513146888622465026?s=20&amp;t=-RaaMeprXjvHQbWq149HzA\" target=\"_blank\" rel=\"noopener\">notable recent example<\/a> &#8212; speedy recovery!) The reasons are poorly understood why this happens to some unlucky few (OK, not understood at all), and it&#8217;s rare, but all of us have seen these unfortunate cases. Could nirmatrelvir\/r reduce the risk for severe disease even in this population?<\/p>\n<p>Highly plausible. Look at the interim results of EPIC-SR which, though not showing benefit in the primary endpoint of time to symptom resolution, <a href=\"https:\/\/s28.q4cdn.com\/781576035\/files\/doc_presentation\/2021\/12\/17\/COVID-Analyst-and-Investor-Call-deck_FINAL.pdf\" target=\"_blank\" rel=\"noopener\">did appear to yield clinical benefits for this prespecified clinical endpoint<\/a>:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-10412\" src=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM.png\" alt=\"\" width=\"543\" height=\"271\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM.png 2022w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM-300x150.png 300w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM-1024x511.png 1024w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM-768x384.png 768w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2022\/04\/Screen-Shot-2022-04-12-at-6.04.58-AM-1536x767.png 1536w\" sizes=\"auto, (max-width: 543px) 100vw, 543px\" \/><\/p>\n<p>A further advantage is the virologic response, which should reduce the likelihood of onward transmission. For those needing negative antigen tests prior to returning to work or school, it&#8217;s another plus to hasten this process.<\/p>\n<p>Also, there&#8217;s the theoretical benefit that treatment will reduce the risk for long COVID, or other <a href=\"https:\/\/twitter.com\/michaelmina_lab\/status\/1512255733991190529?s=20&amp;t=98ShI7A1Kv-a6pJMJXbsbw\" target=\"_blank\" rel=\"noopener\">prolonged post-infectious symptoms.<\/a> Both most certainly occur in people at low-risk for severe disease. Since at its genesis these are virus-induced complications, it&#8217;s not crazy to think that inhibiting and shortening viral replication will make these dreaded outcomes less likely. It will be challenging (and take some time) to prove, but it&#8217;s an important part of the research agenda.<\/p>\n<p>Finally, treating symptomatic COVID-19 falls right in line with the first principles of our specialty. If there&#8217;s a safe, effective, and readily available treatment or prevention strategy for a symptomatic infection that is potentially serious, we treat it &#8212; even if most people will do fine.<\/p>\n<p>I&#8217;m not alone in my view, obviously &#8212; 52% of respondents agreed.\u00a0One respected ID researcher (who recently experienced her own household outbreak that was &#8220;not fun&#8221;), emailed me:<\/p>\n<blockquote><p>I agree with you 100%! I almost commented on that poll to say I thought it was a no-brainer but then saw how many people disagreed and stayed quiet!\u00a0If it cuts short viral replication, the impact on secondary transmission could be enormous &#8212; far more than our vaccine responses are doing. What a huge benefit that could be!<\/p><\/blockquote>\n<p>The opposing view says it&#8217;s not yet been shown to benefit this population of lower-risk people. That these clinical endpoint results are &#8220;fragile&#8221; &#8212; so few outcomes that it could be an accident (and maybe motivated the increased sample size in the EPIC-SR study). That even if there is a clinical benefit, the number needed to treat will be gigantic. That resistance may develop. That the reduction in transmission effect isn&#8217;t proven. That there are places that don&#8217;t have this treatment at all, and our\u00a0indiscriminate prescribing of nirmatrelvir\/r will prevent it from being available abroad.<\/p>\n<p>Lots of echoes of the <a href=\"https:\/\/theconversation.com\/controversies-in-medicine-the-rise-and-fall-of-the-challenge-to-tamiflu-38287\" target=\"_blank\" rel=\"noopener\">oseltamivir controversies<\/a> over the years.\u00a0These are valid concerns, all of them.\u00a0So I really do get this opposing view.<\/p>\n<p>It&#8217;s just not mine.<\/p>\n<p>What do you think?<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The top recommended treatment for high-risk outpatients with COVID-19 in the NIH Guidelines is nirmatrelvir\/r (Paxlovid). It&#8217;s quite clear why. In the EPIC-HR study, unvaccinated people at high risk for severe outcomes had an 89% reduction in the risk for hospitalization or death compared to placebo. If we just look at mortality &#8212; another important [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,8,9],"tags":[4601,5830],"class_list":["post-10411","post","type-post","status-publish","format-standard","hentry","category-health-care","category-patient-care","category-policy","tag-covid-19","tag-nirmatrelvir"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10411","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=10411"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/10411\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=10411"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=10411"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=10411"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}