{"id":27985,"date":"2015-03-24T09:20:45","date_gmt":"2015-03-24T09:20:45","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=27985"},"modified":"2015-03-24T16:14:00","modified_gmt":"2015-03-24T16:14:00","slug":"weekend-off-art-is-non-inferior-to-continuous-art-in-young-people-taking-efavirenz-based-regimens-results-from-breather-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/27985","title":{"rendered":"Weekend-off ART is non-inferior to continuous ART in young people taking efavirenz-based regimens: results from BREATHER study"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

\"CROI<\/p>\n

Viral load suppression taking ART five days on and two days off (short cycle therapy) was non-inferior to that achieved with continuous therapy in young people receiving efavirenz-based first line treatment, at 48 weeks. These results from the BREATHER trial were presented as a late breaker at CROI 2015.<\/strong><\/p>\n

Young people have reported difficulties with adherence during weekend, especially when socialising. BREATHER was designed to exploit the pharmacokinetics of long acting drugs such as efavirenz and look at whether a weekend off treatment strategy was feasible in this population.<\/p>\n

Karina Butler from Our Lady’s Children’s Hospital, Dublin, Ireland presented the results on behalf of the BREATHER investigators.<\/p>\n

BREATHER is a randomised, Phase 2, multicentre, non-inferiority trial conducted in 11 countries. Young people 8 to 24 years of age were eligible if they had a stable viral load <50 copies\/mL and no previous virological failure, CD4 > 350 cells\/mm3 and were receiving efavirenz plus two NRTIs. They were randomised to continue daily ART or change to short cycle therapy.<\/p>\n

Follow up was for a minimum of 48 weeks, with study visits at 0, 4 and 12 weeks, then 12-weekly. The primary outcome was the difference between arms in proportion with viral load >50 copies\/mL at 48 weeks, using Kaplan-Meier estimation method adjusted for region and age. The non-inferiority margin was 12%.<\/p>\n

A total of 199 young people were randomised: 99 to short cycle and 100 to continuous therapy. They were regionally diverse: 35% Uganda, 18% Thailand, 6% Argentina and 41% Europe and US.<\/p>\n

Because of concerns about the trial there was a pilot phase with 32 participants and more intensive monitoring, including viral load testing on Monday mornings, before resuming ART.<\/p>\n

The median age of the participants was 14.1 years (IQR: 11.9 – 17.6); 90% were vertically infected; 56% were black, 21% white and 19% Asian. Their median CD4 was 735 cells\/mm3 (IQR: 575.5 – 967.5). One fifth of the population was over 18 years of age: 39%, 8 to 13; 40%, 13 to 18; and 21%, 18 to 24.<\/p>\n

Median follow up was 85 weeks, with >98% of clinic visits attended up to week 48. Only one participant was lost to follow up by week 48.<\/p>\n

Participants reported taking >95% of scheduled drugs in an adherence questionnaire – and this also revealed 27% decreased drug exposure in the short cycle therapy arm. A substudy using MEMs caps in 61 participants (but only 46 by week 48 – MEMs caps were not popluar) showed median weekly cap openings of 5 and 7 in the short cycle and continuous therapy arms, respectively.<\/p>\n

At 48 weeks, 6 vs 7 participants in the short cycle and continuous therapy arms had detectable viral load >50 copies\/mL. This gave a difference of -1.2% (90% CI, -7.3 to 4.9) in favour of short cycle therapy. The upper bound of difference between Kaplan Meier survival curves of 4.9% was inside the non-inferiority margin of 12%.<\/p>\n

There were 4 vs 11 changes in ART regimen in the short cycle vs continuous therapy arms, p=0.1, NS. The changes were: 8 for toxicity, 4 for simplification, 2 for adherence and 1 for viral failure.<\/p>\n

There were no differences in clinical, immunologic or virologic parameters, inflammatory markers, or resistance among participants with virologic failure.<\/p>\n

Short cycle therapy was popular in a qualitative substudy: 74% of participants said this strategy made things a lot easier and the remainder a little easier. Notably the participants reported fewer side effects at weekends and these had often not previously been disclosed to caregivers.<\/p>\n

Pre- and post-trial questionnaires comparing the two strategies showed modest improvement in most things participants found difficult with continuous ART. Only “going out with friends” was statistically significant, p=0.001.<\/p>\n

Most participants are continuing follow up for an additional two years.<\/p>\n

Comment<\/h3>\n

During the presentation and at the press conference following, it was emphasised that this study was conducted in a carefully selected group of participants. This included a previous history of viral suppression on their first regimen and close to 100% adherence on weekdays. This is not likely to be suitable for everyone.<\/strong><\/p>\n

It is notable that not all the participants were on tenofovir containing regimens – which also has a long half- life. A considerable proportion, particularly in Uganda, received AZT.<\/strong><\/p>\n

Reference:<\/p>\n

Butler KM et al. ART with weekends off is noninferior to continuous ART in young people on EFV+2NRTI. 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015), 23-26 February 2015, Seattle. Oral abstract 38LB.
\nAbstract:
\nhttp:\/\/www.croiconference.org\/sessions\/art-weekends-noninferior-continuous-art-young-people-efv2nrti<\/a>
\nWebcast:
\nhttp:\/\/www.croiwebcasts.org\/console\/player\/25558<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Viral load suppression taking ART five days on and two days off (short cycle therapy) was non-inferior to that achieved with continuous therapy in young people receiving efavirenz-based first line treatment, at 48 weeks. These results …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,41,32],"tags":[187],"class_list":["post-27985","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-treatment-strategies","category-paediatric-care","tag-croi-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27985","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=27985"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27985\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=27985"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=27985"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=27985"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}