{"id":932,"date":"2015-12-23T16:00:36","date_gmt":"2015-12-23T16:00:36","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=932"},"modified":"2017-08-21T11:12:51","modified_gmt":"2017-08-21T11:12:51","slug":"primary-care-corner-with-geoffrey-modest-md-hiv-therapy-without-nrtis","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/12\/23\/primary-care-corner-with-geoffrey-modest-md-hiv-therapy-without-nrtis\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: HIV Therapy Without NRTI&#8217;s"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest <\/strong><\/p>\n<p>The vast majority of recommended HIV drug regimens include tenofovir (TDF)\/emtricitabine (FTC) or abacavir (ABC)\/lamivudine (3TC) as the nucleoside\/tide reverse transcriptase inhibitor (NRTI) backbone.\u00a0From the 2015 HIV\u00a0guidelines (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/04\/17\/primary-care-corner-with-geoffrey-modest-md-updated-hiv-guidelines-2015\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/04\/17\/primary-care-corner-with-geoffrey-modest-md-updated-hiv-guidelines-2015\/<\/a>\u00a0for review) \u200bof\u00a0the 5 initial\u00a0recommended regimens, all have NRTI backbones:\u00a04 include TDF\/FTC and one has ABC\/3TC. Similarly,\u00a0of the\u00a02 NNRTI-based (non-nucleoside reverse transcriptase inhibitor)\u00a0and 4 PI-based (protease inhibitor)\u00a0alternative regimen options, 5 have TDF\/FTC and 1 has ABC\/3TC as the backbone;\u00a0and of the &#8220;other regimen options&#8221;, 5 have either ABC\/3TC or TDF\/FTC. For those &#8220;who cannot have TDF or ABC&#8221;, there is only one which is NRTI-free: darunavir\/ritonavir (DRV\/r) plus raltegravir (RAL), with the caveat not to\u00a0use if the HIV viral load is &gt;100K copies\/ml. For treatment-experienced patients, they recommend\u00a0at least 2 and preferably 3 fully active agents. They\u00a0comment that a boosted PI plus an INSTI (integrase strand transfer inhibitor)\u00a0may be a viable option in patients with no INSTI resistance\u200b, as the only mention of an\u00a0NRTI-free regimen. So, almost all of the studies and\u00a0recommendations include an NRTI backbone.\u00a0In this light, there was a recent article looking specifically at the efficacy of NRTI-free regimens in treatment-experienced patients failing therapy (See\u00a0Ann Intern Med. 2015;163:908-917).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>360 people (26% women, median age 46, 32% white\/41%black\/23% hispanic, 80% with HIV viral load\u00a0&lt;50K, median CD4\u00a0of 207,\u00a047% with\u00a0AIDS)\u00a0who were treatment-experienced with HIV infections and had viral resistance (though\u00a066% were sensitive\u00a0to TDF, 30% to 3TC, 29% to FTC, 40% to AZT, 49% to ABC)\u00a0from 2008-2011. All had been on PI-based therapy and had either used or were\u00a0found to be resistant to some\u00a0NRTIs and NNRTIs.<\/li>\n<li>Put on\u00a0open-label optimized regimens not including NRTIs,\u00a0based on treatment history and resistance testing, then were\u00a0randomized to adding or omitting NRTIs.<\/li>\n<li>For the optimized regimens, they\u00a0assessed the cPSS (continuous phenotypic susceptibility)\u00a0score, a research tool to\u00a0measure antiretroviral activity, making sure it was greater than\u00a02 (this score is the sum of the scores of the individual agents used, where a score of &#8220;1&#8221; signified that the HIV was susceptible to the drug, &#8220;0&#8221; if resistant, and the continuum from 0-1 if there were partial resistance, reflecting the degree of resistance from the upper limit of &#8220;non-resistant&#8221; to the lower-limit of &#8220;resistant&#8221; &#8212; see their Appendix Table 1 for details).<\/li>\n<li>93% completed a 48-week visit<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>\u200bThe optimized regimens turned out to be: RAL (raltegravir)+DRV\/r(darunavir\/ritonavir)+ETR\u00a0(etravirine) in 56%; RAL+DRV\/r+MVC (maraviroc) in 14%, and about 8% each\u00a0to RAL+DRV\/r+ETR+MVC, RAL+ETR+MVC, RAL+DRV\/r+ETR+ENF (enfuvirtide), or other<\/li>\n<li>\u200bThe added NRTI mix was 81% TDF+(3TC or FTC); 14%\u00a0TDF+(3TC or FTC)+AZT;\u00a06% other<\/li>\n<li>Cumulative probability of treatment failure was:\n<ul>\n<li>8% in the omit-NRTI group vs\u00a025.9% in the add-NRTI group (nonsignificant)<\/li>\n<li>No difference in \u00a0primary safety endpoints or % of people achieving HIV viral load &lt;50 copies\/ml<\/li>\n<li>No deaths in the omit-NRTI group vs 7 in the add-NRTI one<\/li>\n<\/ul>\n<\/li>\n<li>Conclusion was that it&#8217;s okay to omit NRTIs in these patients starting a new optimized regimen, thereby reducing pill burden, cost, and toxicities.<\/li>\n<\/ul>\n<p>So, this is a useful article for patients either with broad HIV resistance to NRTIs, or to patients who are intolerant of them (and I have had one treatment-naive patient\u00a0who pretty\u00a0clearly developed a neuropathy to 3TC, thereby\u00a0eliminating\u00a0virtually\u200b\u00a0all of the current and past recommended initial therapies). The basic approach in the past was to include NRTIs, even if there were resistance (e.g., continuing the pressure of 3TC on the virus\u00a0in patients resistant to 3TC\u00a0selected a less-fit and less-aggressive virus). This article shows that with our newer and better and easier-to-take and tolerate regimens, there is no compelling reason to add an NRTI-based backbone, even though a pretty good % of the patients in this study\u00a0were in fact not resistant to them.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: HIV Therapy Without NRTI&#8217;s [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/12\/23\/primary-care-corner-with-geoffrey-modest-md-hiv-therapy-without-nrtis\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-932","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/932","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=932"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/932\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=932"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=932"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=932"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}