{"id":38778,"date":"2020-08-28T07:43:50","date_gmt":"2020-08-28T07:43:50","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=38778"},"modified":"2020-08-28T09:07:47","modified_gmt":"2020-08-28T09:07:47","slug":"dolutegravir-non-inferior-to-efavirenz-at-week-96-in-the-namsal-study-but-associated-with-substantial-weight-gain","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/38778","title":{"rendered":"Dolutegravir non-inferior to efavirenz at week 96 in the NAMSAL study but associated with substantial weight gain"},"content":{"rendered":"

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

Week 96 results from NAMSAL confirmed non-inferior efficacy of dolutegravir (DTG)- vs efavirenz (EFV)-based ART reported at week 48 and no emergence of DTG resistance. [1]<\/strong><\/p>\n

Virological suppression remained lower in participants with a high baseline viral load (across both study \u00a0arms). There was continuous weight gain in the DTG arm.\u00a0These results were presented at AIDS 2020.<\/p>\n

NAMSAL (ANRS 12313) is a phase 3 randomised, open label, multicentre study conducted at three sites in Yaound\u00e9, Cameroon. ART-naive adults with viral load >1000 copies\/mL were randomised to DTG 50 mg or EFV 400 mg once daily, both with tenofovir disoproxil fumarate (TDF)\/lamivudine (3TC).<\/p>\n

The primary endpoint was the proportion of participants with <50 copies\/mL at week 48 and week 96 (10% non-inferiority margin). Week 48 data showing non-inferiority of DTG were reported previously. [2] At this timepoint a notably fewer participants with >100,000 copies at baseline achieved viral suppression <50 copies\/mL compared with those with <100,000 copies\/mL.<\/p>\n

A total of 613 participants were randomised, received at least one dose of study drug and were included in the ITT analysis: 310 DTG arm and 303 EFV 400 mg arm.<\/p>\n

Participants were a median of 36 years old, 68% were women and baseline BMI was 23 kg\/m2<\/sup>. There were no differences between the treatment arms.<\/p>\n

At week 96, the proportion of participants with viral load <50 copies\/mL was 73.9% (229\/310) and 72.3% (219\/303) respectively: difference 1.6% (95% CI -5.4 to 8.6), p=0.66.<\/p>\n

The differences in suppression observed at week 48, when stratified by viral load, persisted.<\/p>\n

Among participants with <100,000 copies\/mL at baseline, 80.6% (83\/103) in the DTG arm and 82.5% (85\/105) in the EFV 400 mg arm achieved viral suppression, compared to 70.5% (146\/207) and 67% (134\/200) of those in the respective arms with baseline viral load >100,000 copies\/mL.<\/p>\n

For participants with baseline viral load >500,000 copies these respective proportions were 66.7% (62\/93) and 70.5% (67\/95) in the DTG and EFV 400 arms.
\nAt week 48, 15 participants in the EFV 400 mg and none in the DTG arm had NNRTI and NRTI resistance. By week 96, a further six participants had developed resistance. Of these three participants in the DTG arm had been switched to EFV 400 mg following the 2018 WHO safety alert on periconception DTG.<\/p>\n

Weight gain observed at week 48 persisted. At week 96 this increase was 6.7 kg in the DTG arm and 4.2 kg in the EFV arm, p<0.001.<\/p>\n

By week 96, weight gain >10% occurred in 45% of participants in the DTG arm (increasing from 38% at week 48) and 33% (from 29%) among those in the EFV arm, p=0.004. Obesity incidence was 22% and 16% in the respective arms. Weight gain was more pronounced in women than men.<\/p>\n

There were 58 (19%) and 46 (15%) adverse events reported in the DTG and EFV arms, respectively.<\/p>\n

Among the 404 women receiving ART in the study there were 62 pregnancies: 27 and 35 in the DTG and EFV arms, respectively. Fourteen pregnancies were ongoing at the time of analysis. There was no vertical transmission among the 26 live births.<\/p>\n

The investigators concluded that these data confirm the non-inferiority of DTG vs EFV but DTG is associated with substantial and continuous weight gain.<\/p>\n

Reference<\/p>\n

    \n
  1. Kouanfack C et al. Dolutegravir- versus low-dose Efavirenz-based regimen for the initial treatment of HIV-1 infection in Cameroon: Week 96 results of the ANRS 12313 \u2013 NAMSAL trial. AIDS 2020 virtual. 6\u201310 July 2020. Oral abstract OAB0402.
    \nhttps:\/\/cattendee.abstractsonline.com\/meeting\/9289\/presentation\/791<\/a><\/li>\n
  2. Clayden P. Dolutegravir non-inferior to low dose efavirenz in real-life African study conducted in Cameroon. HTB. (13 November 2020).
    \n    https:\/\/i-base.info\/htb\/35235<\/a><\/li>\n<\/ol>\n

    This article was originally posted on 20 August 2020.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Week 96 results from NAMSAL confirmed non-inferior efficacy of dolutegravir (DTG)- vs efavirenz (EFV)-based ART reported at week 48 and no emergence of DTG resistance. [1] Virological suppression remained lower in participants with a high baseline …<\/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],"tags":[295],"class_list":["post-38778","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-treatment-strategies","tag-aids2020"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38778","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=38778"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38778\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=38778"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=38778"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=38778"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}