{"id":2809,"date":"2012-06-08T06:47:07","date_gmt":"2012-06-08T10:47:07","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=2809"},"modified":"2015-06-04T15:14:34","modified_gmt":"2015-06-04T19:14:34","slug":"spartan-two-drug-nrti-sparing-strategies-continue-to-disappoint","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/spartan-two-drug-nrti-sparing-strategies-continue-to-disappoint\/2012\/06\/08\/","title":{"rendered":"SPARTAN: Two-Drug, NRTI-Sparing Strategies Continue to Disappoint"},"content":{"rendered":"

\"\"<\/a>Just published is the cleverly named “SPARTAN” study<\/a> — spartan<\/a> because it leaves out both NRTIs and<\/em> ritonavir\u00a0— and the results are very interesting.<\/p>\n

Ninety-three treatment-naive HIV-positive study subjects were randomized 2:1 to receive either a two-drug regimen of raltegravir 400 mg BID + atazanavir 300 mg BID, or\u00a0a standard regimen of TDF\/FTC + boosted atazanavir. (The higher ATV dose in the two-drug arm targeted ATV exposures comparable to those achieved by ritonavir-boosting.)<\/p>\n

At week 24, virologic suppression rates numerically favored the two-drug regimen (75% vs 63%); as a small pilot study, the trial was not powered for a statistical comparison between the two arms. As has been observed in other studies of integrase inhibitors, the non-integrase group had a slower initial response and appeared to be catching up.<\/p>\n

Despite these early favorable results, there were 6 virologic failures in the RAL + ATV group — vs only 1 in the standard arm — and 4 of these failures showed evidence of raltegravir resistance. Notably, all 4 of these patients with resistance had baseline HIV RNA > 100,000, a similar finding to ACTG 5162<\/a>\u00a0(which examined RAL + darunavir\/r). Rates of grade 3-4 and grade 4 hyperbilirubinemia were also higher in the ATV + RAL arm. Based on these efficacy and safety results, the sponsor elected to terminate the study.<\/p>\n

As I’ve noted before<\/a>, initial two-drug HIV therapy without NRTIs hasn’t fared well, even when it includes our best drugs. In addition,\u00a0we still don’t know why these two-drug regimens don’t do as well, especially in patients with high viral loads.<\/p>\n

Furthermore, the protective effect that boosted PIs have on the development of NRTI resistance doesn’t apply either to NNRTIs (as shown in ACTG 5142<\/a>) or to raltegravir (again, ACTG 5162). And though in SPARTAN ritonavir-boosting wasn’t used, it doesn’t appear we can blame PK, as ATV exposures indeed were comparable to those seen with ATV\/r dosed at 300\/100 mg daily. Do the NRTIs provide some key antiviral component mechanistically? Do we just not have the right<\/em> two active drugs? Or is there something magic about using 3 rather than 2 drugs, regardless of mechanism of action?<\/p>\n

Suffice to say, the results of the fully powered NEAT study<\/a> — which compares RAL to TDF\/FTC, with all study subjects receiving boosted darunavir — will be of great interest, as will a similar study that uses maraviroc<\/a> instead of raltegravir.<\/p>\n","protected":false},"excerpt":{"rendered":"

Just published is the cleverly named “SPARTAN” study — spartan because it leaves out both NRTIs and ritonavir\u00a0— and the results are very interesting. Ninety-three treatment-naive HIV-positive study subjects were randomized 2:1 to receive either a two-drug regimen of raltegravir 400 mg BID + atazanavir 300 mg BID, or\u00a0a standard regimen of TDF\/FTC + boosted […]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,4,5,10],"tags":[87,779,817,866,909],"class_list":["post-2809","post","type-post","status-publish","format-standard","hentry","category-health-care","category-hiv","category-infectious-diseases","category-research","tag-atazanavir","tag-raltegravir","tag-ritonavir","tag-spartan","tag-tenofovirftc"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/2809","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=2809"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/2809\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=2809"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=2809"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=2809"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}