{"id":13806,"date":"2010-08-26T12:05:32","date_gmt":"2010-08-26T12:05:32","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=13806"},"modified":"2012-07-27T10:23:42","modified_gmt":"2012-07-27T10:23:42","slug":"unboosted-twice-daily-atazanavir-plus-raltegravir","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/13806","title":{"rendered":"Unboosted twice-daily atazanavir plus raltegravir"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

A phase 2b comparison study compared an experimental unboosted combination of atazanavir (ATZ) 300mg plus 400mg raltegravir (RAL), both twice-daily, to boosted atazanavir\/r (300\/100mg) plus tenofovir\/FTC, both once-daily (the SPARTAN study). The results were presented as a late breaker.<\/p>\n

This small study randomised 94 people 2:1 to atazanavir\/raltegravir (n=63) or the control group (n=31). The primary analysis at week 24 (percentage of patients with viral load < 50 copies\/mL) used confirmed virologic response (CVR NC=F). The study was not powered to detect differences between the
\ngroups.<\/p>\n

Baseline characteristics included 90% male, 85% white, mean CD4 250 cells\/mm3 and mean viral log of 4.9 logs with approximately 50% patient having viral load >100,000 copies\/mL.<\/p>\n

About 10% patients in each arm discontinued treatment, all of who were undetectable in the atazanavir\/raltegravir and they remained suppressed to week 24. The raltegravir arm produced a more rapid virological response, with 75% vs 63% undetectable at week 24, with higher CD4 increases in the experimental arm +166 vs +127 cells\/mm3. Viral response rates were slightly higher using less stringent analyses. Of the 11 patients with virlogical failure in the raltegravir arm (>50 copies\/mL; 6\/11 were >400 copies\/mL), eight had baseline viral load >250,000 copies\/mL. Four patients had resistance testing, with 3\/4 showing integrase mutations and the fourth phenotypic resistance. In the control group there were eight failures >50 copies\/mL (4\/8 with baseline viral load >250,000 copies\/mL) but only one at >400 copies\/mL. No resistance was indentified to atazanavir in either arm.<\/p>\n

A PK substudy showed approximately 39% increased AUC and 30% increased Cmin for atazanavir twice-daily compared to levels seen with ritonavir boosted plus tenofovir.<\/p>\n

Side effects were broadly similar, except significantly higher bilirubin levels in the raltegravir arm (60% vs 43% grade 3\/4; and 20% vs 0% grade 4). Lipid differences included higher HDL cholesterol and lower triglycerides in the raltegravir arm. LDL and total cholesterol were similar.<\/p>\n

These differences, together with no virological benefits compared to standard of care regimens, and the twice-daily regimen, were sufficient for BMS to close the study early.<\/p>\n

comment<\/h2>\n

For UK patients at least, the cost of double-dose atazanavir plus raltegravir would limit the use of this combination, even if the results had been more successful.<\/strong><\/p>\n

Reference:<\/p>\n

    \n
  1. Kozal MJ et al. The SPARTAN study: a pilot study to assess the safety and efficacy of an investigational NRTI- and RTV-sparing regimen of atazanavir (ATV) experimental dose of 300mg BID plus raltegravir (RAL) 400mg BID (ATV+RAL) in treatment-naive HIV-infected subjects. 18th IAS Conference, 18\u009623 July 2010, Vienna. Vienna. Late breaker abstract THLBB204. http:\/\/pag.aids2010.org\/Abstracts.aspx?SID=1990&AID=17423<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base A phase 2b comparison study compared an experimental unboosted combination of atazanavir (ATZ) 300mg plus 400mg raltegravir (RAL), both twice-daily, to boosted atazanavir\/r (300\/100mg) plus tenofovir\/FTC, both once-daily (the SPARTAN study). The results were presented as …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[153],"class_list":["post-13806","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-aids-18th-vienna-2010"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/13806","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=13806"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/13806\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=13806"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=13806"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=13806"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}