{"id":30376,"date":"2016-08-01T09:24:50","date_gmt":"2016-08-01T09:24:50","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=30376"},"modified":"2016-08-14T19:02:07","modified_gmt":"2016-08-14T19:02:07","slug":"dolutegravir-is-superior-to-boosted-atazanavir-in-women-in-the-aria-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/30376","title":{"rendered":"Dolutegravir is superior to boosted atazanavir in women in the ARIA study"},"content":{"rendered":"

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

Dolutegravir-based ART was superior to a boosted atazanavir-based regimen in treatment naive women at 48 weeks, according to data from the ARIA study presented at AIDS2016.<\/strong><\/p>\n

The ARIA study was performed to provide additional data on women receiving the dolutegravir (DTG)-based fixed dose combination (FDC) in which it is co-formulated with abacavir (ABC) and lamivudine (3TC). [1] The FDC is marketed by ViiV Healthcare as Triumeq and was first approved in August 2014 in the US. [2]<\/p>\n

The study is multi-national, multi-site, open label, randomised, non-inferiority, phase 3b. It is ongoing and enrollment was from September 2013 to September 2014<\/p>\n

Catherine Orrell from the University of Cape Town presented 48-week data, on behalf of the ARIA investigators, in an oral late breaker. [3]<\/p>\n

Eligible women were: ART-naive, HLA-B*5701 negative, with viral load 500 copies\/mL or more and hepatitis B negative. They were randomised 1:1 to 48 weeks of treatment with DTG\/ABC\/3TC or atazanavir\/ritonavir plus tenofovir DF\/emtricitabine (ATV\/r + TDF\/FTC) once daily, and stratified by viral load less than or above 100, 000 copies\/mL and CD4 count less than or above 350 cells\/mm3.<\/p>\n

Women who became pregnant during the course of the study were withdrawn and offered entry into a DTG\/ABC\/3TC pregnancy study. [4]<\/p>\n

The primary endpoint was the proportion of women with viral load <50 copies\/mL at week 48 using the FDA Snapshot algorithm (-12% non-inferiority margin).<\/p>\n

A total of 495 women were randomised and treated: 248 and 247 in the DTG\/ABC\/3TC and ATV\/r + TDF\/FTC arms respectively. The women were a median age of 37 years; approximately 43% were of African origin, 45% were white and 22% were Asian. About half of the participants had CD4 <350 cells\/mm3 and about 28% had viral load >100,000 copies\/mL. Participants were well matched for demographic and baseline characteristics. Of the women in the DTG\/ABC\/3TC arm, 83% (n=206) completed week 48, compared with 78% (192) in the ATV\/r + TDF\/FTC arm.<\/p>\n

Five women in the DTG\/ABC\/3TC arm (2%) and eight in the ATV\/r + TDF\/FTC arm (3%) became pregnant and withdrew from the study.<\/p>\n

In ITT analysis, DTG\/ABC\/3TC was superior to ATV\/r + FTC\/TDF at 48 weeks: 82% vs 71% of participants had viral load <50 copies\/mL respectively, adjusted difference 10.5% (95% CI: 3.1% to 17.8%), p=0.005.<\/p>\n

Differences in response were driven by Snapshot virologic non-response (6% vs 14%) and fewer discontinuations due to adverse events or death (4% vs 7%) in the DTG\/ABC\/3TC arm.<\/p>\n

No participant receiving DTG\/ABC\/3TC developed INSTI or ABC\/3TC resistance. DTG\/ABC\/3TC had a favourable safety profile to ATV\/r + TDF\/FTC and a similar overall profile for DTG to that reported in previous studies.<\/p>\n

Comment<\/h3>\n

The participants in the registrational studies (typically for such studies) were approximately 80% men (and few non-white participants), so this clinical trial evaluating DTG in women is welcome. More important still is data on pregnant women – which is essential to DTG’s recommendation in the WHO guidelines without restriction.<\/strong><\/p>\n

As noted above, five (2%) ARIA participants in the DTG\/ABC\/3TC FDC arm and eight (3%) in the ATV\/r + TDF\/FTC arm were discontinued from the randomised phase of the study due to pregnancy.<\/strong><\/p>\n

Of these pregnant women, four in each treatment group had undetectable viral load at the time of discontinuation. Two additional women became pregnant in the DTG\/ABC\/3TC FDC treatment group during the continuation phase of the study.<\/strong><\/p>\n

Of the seven women who became pregnant in the DTG\/ABC\/3TC arm (including during the continuation phase), three resulted in a normal infant with no apparent congenital anomaly, two women elected to terminate the pregnancy, one woman experienced an anembryonic pregnancy, and the outcome of one pregnancy was unknown.<\/strong> [5]<\/p>\n

Other studies looking at DTG in pregnancy are described in Fit for Purpose 2016.<\/strong> [6]<\/p>\n

References:<\/p>\n

    \n
  1. US National Institutes of Health. A study to determine safety and efficacy of dolutegravir\/abacavir\/lamivudine (DTG\/ABC\/3TC) in Human Immunodeficiency Virus (HIV)-1 infected antiretroviral therapy (ART) naive women (ARIA).
    \nhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT01910402<\/a><\/li>\n
  2. ViiV Healthcare (press release). ViiV Healthcare receives FDA approval for Triumeq. 22 August 2014.
    \n    https:\/\/www.viivhealthcare.com\/media\/press-releases\/2014\/august\/viiv-healthcare-receives-fda-approval-for-triumeq.aspx<\/a><\/li>\n
  3. Orrell C et al. Superior efficacy of dolutegravir\/abacavir\/lamivudine (DTG\/ABC\/3TC) fixed dose combination (FDC) compared with ritonavir (RTV) boosted atazanavir (ATV) plus tenofovir disoproxil fumarate\/emtricitabine (TDF\/FTC) in treatment-naive women with HIV-1 infection (ARIA Study). AIDS2016. Oral abstract THAB0205LB.
    \n    http:\/\/programme.aids2016.org\/Abstract\/Abstract\/10215<\/a><\/li>\n
  4. US National Institutes of Health. ING200336, pharmacokinetic and safety study in pregnant women with human immuno virus infection.
    \n    https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02075593<\/a><\/li>\n
  5. Questions to Dr Orrell following the presentation and personal communication from ViiV Healthcare.<\/li>\n
  6. Clayden P. Fit for purpose: antiretroviral treatment optimisation. i-Base. 14 July 2016.
    \n    https:\/\/i-base.info\/htb\/30195<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Dolutegravir-based ART was superior to a boosted atazanavir-based regimen in treatment naive women at 48 weeks, according to data from the ARIA study presented at AIDS2016. The ARIA study was performed to provide additional data on …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,44,35],"tags":[224],"class_list":["post-30376","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-womens-health","category-pmtct-and-maternal-health","tag-aids-21st-2016-durban"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/30376","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=30376"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/30376\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=30376"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=30376"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=30376"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}