{"id":19937,"date":"2012-08-01T13:01:53","date_gmt":"2012-08-01T13:01:53","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=19937"},"modified":"2012-08-16T17:34:54","modified_gmt":"2012-08-16T17:34:54","slug":"dolutegravir-vs-raltegravir-in-treatment-naive-patients-48-week-results-from-the-spring-2-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/19937","title":{"rendered":"Dolutegravir vs raltegravir in treatment-naive patients: 48 week results from the SPRING 2 study"},"content":{"rendered":"

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

Francois Raffi, from University of Nantes, France, presented the SPRING-2 study as an oral late breaker.<\/strong><\/p>\n

This was a randomised, double-blind, double-placebo controlled, non-inferiority study in treatment-naive patients. Participants (from Canada, US, Australia and Europe) were randomised (1:1; n=411 in each arm) to receive either 50 mg dolutegravir once-daily or 400 mg raltegravir twice-daily (plus matching placebo) with investigator selected tenofovir\/FTC (60%) or abacavir\/3TC (40%), stratified by baseline viral load (above and below 100,000 copies\/mL) and by NRTI choice. The primary endpoint was viral suppression to <50 copies\/mL with a lower margin confidence interval set at \u201310% to determine non-inferiority.<\/p>\n

This was a largely white, male study population in patients with early-stage HIV. Approximate baseline characteristics for the study included median age of 36 years, 85% male, 85% white and 10% African American. Median viral load and CD4 count were approximately 35,000 copies\/mL and 360 cells\/mm3 respectively. No figures for the range or IQR were provided for the median values. However, 28% of patients had baseline viral load >100,000 copies\/mL and 12% had a CD4 count <200 cells\/mm3. Approximately 2% and 10% were coinfected with hepatitis B and C respectively.<\/p>\n

Viral efficacy rates were 88% for dolutegravir and 85% for raltegravir, which, after adjusting for baseline viral load and NRTI, met the criteria for non-inferiority (difference 2.5%; 95% CI: -2.2% to 7.1%). Dolutegravir had a similarly rapid, or perhaps slightly faster, response compared to the already racy drop seen with raltegravir, with 70% of patients undetectable by week 4 and >80% by week 8.<\/p>\n

Discontinuations were similar between the dolutegravir and raltegravir arms (11% vs 14%) and occured for similar reasons (4% vs 6% for lack of efficacy, 3% each for protocol violations, 2% each for side effects, and <1% vs 2% for each of loss to follow up and withdrawal of consent).<\/p>\n

There were 7% of patients in each arm without 48-week data, with these discontinuations driven predominantly by reasons other than side effects.<\/p>\n

Median CD4 counts increases were similarly close at weeks 8, 24 and 48: +88, +182 and +230 cells\/mm3 in each arm.<\/p>\n

Stratification by baseline viral load and nucleoside\/tide use also met non-inferiority endpoints. Response rates were 90% vs 89% with <100,000 copies\/mL (difference 0.4; 95%CI -4.5, 5.3) and 82% vs 75% (difference: 7.5; 95%CI -3.1, 18.0) with >100,000 copies\/mL; and 86% vs 87% using abacavir\/3TC (difference \u20130.8; 95%CI \u20138.2, 6.6) and 89% vs 85% using tenofovir\/FTC (difference 4.6; 95%CI \u20131.3, 10.6) \u2013 all dolutegravir vs raltegravir, respectively.<\/p>\n

There were slightly fewer patients with virological failure, defined as confirmed viral load >50 copies\/mL at week 24 or after, in the dolutegravir arm (5% vs 7%; n=20 vs 28) with most (19\/20) being between 50 and 400 copies\/mL. Two patients in the raltegravir arm rebounded to 10-50,000 copies\/mL and one to >100,000 copies\/mL. One of these patients developed integrase inhibitor and NRTI mutations, with NRTI resistance only in three others. No mutations were detected in the dolutegravir arm.<\/p>\n

Tolerability was good in both arms with low numbers of patients with grade 3 (n=2 vs 5) and grade 4 (n=2 vs 0) side effects. Serious adverse events occurred in 7% vs 8% (n=29 vs 31) but were only judged to be drug-related in 3 vs 5 patients. These included arrhythmia, hypersensitivity and hepatitis (dolutegravir) and convulsion (2), hypersensitivity\/hepatitis, diarrhoea (raltegravir). Only 2% of patients in each arm discontinued due to side effects.<\/p>\n

Grade 3\/4 laboratory abnormalities were infrequent and included increases in creatinine phophokinase (5 vs 3%), AST (3 vs 2%) ALT (2 vs 2%) and lipase (2 vs 3%), all dolutegravir vs raltegravir. Slightly higher increases in mean creatinine (+12\/3 vs +4.7 mmol\/L; p=NS) and changes in creatinine clearance (\u201315.5 vs \u20135.4 mL\/min; p=NS) occurred in the dolutegravir arm but dolutegravir does not affect eGFR and there were no discontinuations related to renal events in either arm.<\/p>\n

comment<\/h2>\n

These results show similar levels of efficacy for both integrase inhibitors in treatment-naive easier to treat patients, with good tolerability.<\/strong><\/p>\n

Of note, both drugs also have paediatric formulations currently in development and\/or clinical studies.<\/strong><\/p>\n

Reference:<\/p>\n

Raffi F et al. Once-daily dolutegravir (DTG; S\/GSK1349572) is non-inferior to raltegravir (RAL) in antiretroviral-naive adults: 48 week results from SPRING-2 (ING113086). 19th International AIDS Conference. 22-27 July 2012, Washington. Late breaker oral presentation THLBB04.<\/p>\n

http:\/\/pag.aids2012.org\/abstracts.aspx?aid=20990<\/a><\/p>\n

http:\/\/pag.aids2012.org\/flash.aspx?pid=3888<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Francois Raffi, from University of Nantes, France, presented the SPRING-2 study as an oral late breaker. This was a randomised, double-blind, double-placebo controlled, non-inferiority study in treatment-naive patients. Participants (from Canada, US, Australia and Europe) were …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[161],"class_list":["post-19937","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-aids-19th-washington-2012"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/19937","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=19937"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/19937\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=19937"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=19937"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=19937"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}