{"id":4381,"date":"2013-07-14T21:35:48","date_gmt":"2013-07-15T01:35:48","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=4381"},"modified":"2015-06-04T14:33:21","modified_gmt":"2015-06-04T18:33:21","slug":"will-dolutegravir-instantly-become-the-integrase-inhibitor-of-choice-in-patients-with-treatment-failure","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/will-dolutegravir-instantly-become-the-integrase-inhibitor-of-choice-in-patients-with-treatment-failure\/2013\/07\/14\/","title":{"rendered":"Will Dolutegravir Instantly Become the Integrase Inhibitor of Choice in Patients with Treatment Failure?"},"content":{"rendered":"<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2013\/07\/sailing-in-Boston1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\" wp-image-4382 alignright\" alt=\"sailing in Boston\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2013\/07\/sailing-in-Boston1.jpg\" width=\"320\" height=\"214\" \/><\/a>Here&#8217;s the short answer : Yes. Probably.<\/p>\n<p>And here&#8217;s why.<\/p>\n<p>In a randomized, double blind clinical trial <a href=\"http:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(13)61221-0\/abstract\" target=\"_blank\">just published in the <em>Lancet<\/em><\/a> &#8212; it&#8217;s called SAILING &#8212; once-daily dolutegravir was compared to twice daily raltegravir in treatment-experienced patients. The site investigators could choose one or two other fully active agents to develop an optimized background regimen (OBR). There was a protocol-specified stratification based on fully-active darunavir and baseline viral load.<\/p>\n<p>There were over 700 study subjects; they were recruited from 156 sites, located in every continent except Antarctica.<\/p>\n<p>(Yes, 156 sites. Hey, it&#8217;s hard to find patients who fail treatment who are good candidates for clinical trials!)<\/p>\n<p>And here are the results:<\/p>\n<ul>\n<li><span style=\"line-height: 13px\">Virologic outcome: \u00a0Dolutegravir was superior to raltegravir, 71% suppressed at 48 weeks, vs 64%, p=0.03.<\/span><\/li>\n<li>Those experiencing virologic failure had less resistance on dolutegravir than raltegravir.<\/li>\n<li>In the hardest-to-treat subgroups &#8212; those with no active darunavir in their OBR, or the higher viral load stratum &#8212; the differences favoring dolutegravir over raltegravir were even greater than in study overall.<\/li>\n<li>Adverse events, serious or otherwise &#8212; pretty much the same.<\/li>\n<\/ul>\n<p>Now I&#8217;ve said before that raltegravir is one of our very best antiretroviral agents: it&#8217;s highly potent, well tolerated, has very few drug-drug interactions, an extensive safety record dating back to clinical trials that started in the mid-2000s, and and even more extensive favorable clinical experience since its approval in 2007.<\/p>\n<p>But dolutegravir is once daily, seems just as well tolerated as raltegravir, has a similar drug-drug interaction profile &#8212; and based in the results of SAILING, is probably more potent and less prone to resistance.<\/p>\n<p>Note that elvitegravir isn&#8217;t currently in the discussion, since it&#8217;s not available except as part of this one pill &#8212; TDF\/FTC\/EVG\/COBI &#8212; which can&#8217;t be given with boosted PIs, so is a difficult choice in those with treatment failure.<\/p>\n<p>Bottom line: \u00a0barring some unexpected toxicity when it gets into broader use after approval &#8212; always a possibility &#8212; dolutegravir will instantly become the integrase inhibitor (II, INI, INSTI, InSTI) of choice in treatment experienced patients with treatment failure.<\/p>\n<p>(Still need a <a href=\"http:\/\/blogs.nejm.org\/index.php\/integrase-inhibitors-in-search-of-an-abbreviation\/2009\/09\/18\/\" target=\"_blank\">good abbreviation<\/a> for this drug class.)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Here&#8217;s the short answer : Yes. Probably. And here&#8217;s why. In a randomized, double blind clinical trial just published in the Lancet &#8212; it&#8217;s called SAILING &#8212; once-daily dolutegravir was compared to twice daily raltegravir in treatment-experienced patients. The site investigators could choose one or two other fully active agents to develop an optimized background [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,8,10],"tags":[284,316,423,509,779],"class_list":["post-4381","post","type-post","status-publish","format-standard","hentry","category-hiv","category-patient-care","category-research","tag-dolutegravir","tag-elvitegravir","tag-hiv","tag-integrase-inhibitors","tag-raltegravir"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/4381","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=4381"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/4381\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=4381"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=4381"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=4381"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}