{"id":7845,"date":"2015-11-08T08:42:27","date_gmt":"2015-11-08T13:42:27","guid":{"rendered":"http:\/\/blogs.nejm.org\/hiv-id-observations\/?p=7845"},"modified":"2015-11-08T08:45:36","modified_gmt":"2015-11-08T13:45:36","slug":"new-hiv-treatment-ecf-taf-is-really-all-about-the-taf-part","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/new-hiv-treatment-ecf-taf-is-really-all-about-the-taf-part\/2015\/11\/08\/","title":{"rendered":"New HIV Treatment &#8220;ECF-TAF&#8221; is Really All About the &#8220;TAF&#8221; Part"},"content":{"rendered":"<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/11\/espresso.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-medium wp-image-7860\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/11\/espresso-199x300.jpg\" alt=\"espresso\" width=\"199\" height=\"300\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/11\/espresso-199x300.jpg 199w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/11\/espresso.jpg 299w\" sizes=\"auto, (max-width: 199px) 100vw, 199px\" \/><\/a>HIV providers and patients recently got <a href=\"http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm471300.htm\" target=\"_blank\">this news from the FDA:<\/a><\/p>\n<p style=\"padding-left: 30px\">The U.S. Food and Drug Administration today approved Genvoya (a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older.<\/p>\n<p>(Disclosure: \u00a0I have been involved with the clinical trials;\u00a0you can read my full disclosures <a href=\"http:\/\/www.jwatch.org\/editors\/u027\" target=\"_blank\">here<\/a>. That involvement notwithstanding,\u00a0some sort of\u00a0comment seems appropriate &#8212; this is an HIV\/ID blog, after all.)<\/p>\n<p>The availability\u00a0of\u00a0elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide &#8212; hereafter abbreviated &#8220;ECF-TAF&#8221; &#8212; brings us the fifth one-pill-a-day treatment for HIV. Of course we already have something very similar, which is <a href=\"https:\/\/aidsinfo.nih.gov\/drugs\/507\/stribild\/0\/patient\" target=\"_blank\">ECF-<\/a><a href=\"https:\/\/aidsinfo.nih.gov\/drugs\/507\/stribild\/0\/patient\" target=\"_blank\">TDF<\/a><strong>,<\/strong> and hence the only thing new here is the TAF component.<\/p>\n<p>So what does ECF-TAF\u00a0bring us that we didn&#8217;t already have with ECF-TDF?<\/p>\n<p>Based on multiple clinical studies, here are what I think are the proven differences between the two:<\/p>\n<ul>\n<li><strong>Less effect on bone density.<\/strong>\u00a0As initial therapy, TAF induces less bone loss than TDF &#8212; the former is comparable to NRTI-sparing strategies. Furthermore, in multiple clinical studies, switching from TDF to TAF improves bone density.<\/li>\n<li><strong>Decreased renal toxicity.\u00a0<\/strong>In several\u00a0trials involving over 3000 patients, no case of tenofovir-related renal toxicity has occurred in an ECF-TAF-treated patient.\u00a0TAF&#8217;s\u00a0effect on urinary proteins (a surrogate marker for renal effects) is also\u00a0significantly\u00a0less than TDF. One unknown is whether it can be safely given to a patient with a history of tenofovir-related renal toxicity; that question is under study.\u00a0The regimen is approved for use in patients with estimated GFR down to 30 ml\/min.<\/li>\n<li><strong>A lower milligram dose.<\/strong> As part of ECF-TAF, the dose of TAF is only 10 mg, vs 300 mg for TDF. (When not given with cobicistat or ritonavir, the dose will be 25 mg.) A lower milligram dose means smaller pills and easier coformulations.<\/li>\n<li><strong>A novel\u00a0way to simplify complex regimens.<\/strong> As noted <strong><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/the-most-important-hiv-study-at-idweek-2015\/2015\/10\/29\/\" target=\"_blank\">here<\/a><\/strong>, ECF-TAF can be combined with 800 mg of darunavir to make a two-pill treatment for some patients with multi-drug resistant virus. You couldn&#8217;t do this with ECF-TDF, at least not with confidence &#8212; it hadn&#8217;t been studied, and the three-way drug-drug interaction between cobicistat, darunavir, and elvitegravir gave me pause.<\/li>\n<li><strong>Less\u00a0lipid-lowering effect.<\/strong> Tenofovir lowers\u00a0lipid levels (mechanism still unclear), and since TAF delivers 90% lower blood levels of tenofovir than TDF, there is\u00a0less of this effect. This lower tenofovir exposure is mostly a good thing (see renal and bone above), but not here. I suspect this won&#8217;t be clinically relevant, but of course we don&#8217;t have enough follow-up data since the incidence of cardiovascular events\u00a0in short-term clinical trials is so low.<\/li>\n<\/ul>\n<p>And here&#8217;s what&#8217;s <em>not<\/em> different:<\/p>\n<ul>\n<li><strong>Antiviral activity.<\/strong> Though in phase I studies <strong><a href=\"http:\/\/jac.oxfordjournals.org\/content\/69\/5\/1362.long\" target=\"_blank\">TAF induced greater declines in HIV RNA than TDF<\/a><\/strong>, virologic outcomes (meaning failures and incident resistance) in studies comparing ECF-TAF with ECF-TDF have been similar.<\/li>\n<li><strong>Drug-drug interactions. <\/strong>The &#8220;C&#8221; in both ECF-TAF and ECF-TDF stands for cobicistat, the ritonavir-like PK &#8220;booster&#8221; that is necessary for elivitegravir&#8217;s once-daily dosing. A cytochrome p450 inhibitor, cobicistat has <strong><a href=\"http:\/\/hivinsite.ucsf.edu\/insite?page=ar-00-02&amp;param=225&amp;post=4\" target=\"_blank\">numerous drug-drug interactions<\/a><\/strong> &#8212; watch those medication lists carefully! Note that a combination of TAF\/FTC and 9883 &#8212; an unboosted integrase inhibitor, no cobicistat required &#8212; <strong><a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02397694?term=9883&amp;rank=1\" target=\"_blank\">is in development.<\/a><\/strong><\/li>\n<li><strong>Subjective side effects.<\/strong> There&#8217;s no significant difference in the incidence of patient-reported side effects. In other words, if your patient didn&#8217;t tolerate ECF-TDF, there is little point in trying ECF-TAF. Good news is that both are very well tolerated, with extremely low discontinuation rates for adverse events.<\/li>\n<li><strong>The price.<\/strong> Encouragingly, ECF-TAF is <strong><a href=\"http:\/\/abcnews.go.com\/Business\/wireStory\/gileads-hiv-pill-genvoya-wins-us-approval-35006087\" target=\"_blank\">priced the same as ECF-TDF<\/a><\/strong>, a decision <strong><a href=\"http:\/\/fairpricingcoalition.org\/\" target=\"_blank\">lauded by this group.<\/a><\/strong> However, integrase-inhibitor based regimens remain relatively expensive (average wholesale price around $30,000\/year) compared to NNRTI-based therapies, though cheaper than those that include a boosted PI.<\/li>\n<\/ul>\n<p>Overall, ECF-TAF is welcome new option for treatment, and to emphasize again it&#8217;s the TAF part that makes the (only) difference.\u00a0Future TAF formulations will include TAF-FTC-rilpivirine and TAF-FTC (which will need at least one other active drug) &#8212; these are expected some time next year. TAF-FTC-9883 is further away.<\/p>\n<p>Meanwhile, we can continue to ponder\u00a0the mysteries of choosing a brand name for a drug &#8212; &#8220;Genvoya&#8221; sounds to me like\u00a0a\u00a0<a href=\"http:\/\/www.cnet.com\/news\/fancy-coffeemakers-for-brewing-right-at-home\/\" target=\"_blank\">high-end coffee maker.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>HIV providers and patients recently got this news from the FDA: The U.S. Food and Drug Administration today approved Genvoya (a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older. (Disclosure: \u00a0I have [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,4,8,10],"tags":[205,316,423,1095,901,1092],"class_list":["post-7845","post","type-post","status-publish","format-standard","hentry","category-health-care","category-hiv","category-patient-care","category-research","tag-cobicistat","tag-elvitegravir","tag-hiv","tag-taf","tag-tdf","tag-tenofovir-alafenamide"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/7845","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=7845"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/7845\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=7845"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=7845"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=7845"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}