{"id":40970,"date":"2021-08-01T06:38:36","date_gmt":"2021-08-01T06:38:36","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=40970"},"modified":"2021-08-01T10:16:33","modified_gmt":"2021-08-01T10:16:33","slug":"dolutegravir-superior-to-standard-of-care-in-young-children-results-from-the-odyssey-trial","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/40970","title":{"rendered":"Dolutegravir superior to standard-of-care in young children: results from the ODYSSEY trial"},"content":{"rendered":"<div  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-40971\" class=\"wp-image-40971\" src=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2021\/07\/Paediatric-lgog-2021.png\" alt=\"\" width=\"196\" height=\"196\" \/><p id=\"caption-attachment-40971\" class=\"wp-caption-text\">13th International Workshop on HIV Paediatrics 2021.<\/p><\/div>\n<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>Dolutegravir (DTG)-based ART was superior to standard-of-care in children weighing 3 to 14 kg, starting first- or second-line treatment. <\/strong><\/p>\n<p>These 96 week results from the younger cohort of the ODYSSEY trial were presented at the 13th International Workshop on HIV Paediatrics 2021. [1]<\/p>\n<p>ODYSSEY, a multi-country randomised trial, showed superior efficacy for DTG plus two NRTIs vs standard-of-care in 707 children and adolescents weighing 14 kg or more (median age 12 years), starting first- or second-line ART. These results were presented earlier this year at CROI 2021. [2]<\/p>\n<p>Late breaking results, shown at the workshop, were for an additional cohort of 85 younger children weighing less than 14 kg, who completed 96 weeks follow-up on 28 June 2021.<\/p>\n<p>The children were randomised: 42 to DTG and 43 to standard-of-care (Uganda 43, Zimbabwe 22, South Africa 20).<\/p>\n<p>Their median age was 1.4 years (IQR 0.6 to 2.0); 23 were 3 to &lt;6 kg, 40 were 6 to &lt;10 kg and 22 were 10 to &lt;14 kg. Seventy two children started first-line and 13 started second-line ART; 74% in the standard-of-care arm received boosted lopinavir.<\/p>\n<p>Median follow-up was 120 (IQR 97 to 132) weeks; 5 (6%) children were lost to follow-up.<\/p>\n<p>The investigators performed three analyses to estimate the difference in the probability of clinical\/virological failure by 96 weeks between DTG-based ART and standard-of-care in children weighing &lt;14 kg:<\/p>\n<ul>\n<li>Stand-alone analysis, using data only from children &lt;14 kg.<\/li>\n<li>Pooled analysis, assuming the treatment difference is identical in children &lt;14 kg and <u>&gt;<\/u>14 kg, and combining the two data sets (they allocated a weight of approximately 90% to data from children <u>&gt;<\/u>14 kg).<\/li>\n<li>Bayesian analysis, using information from the 707 children as a prior distribution and clinical opinion todetermine how much weight is given to the that (based on interviews with paediatricians they assigned a weight of 78% to data from the older children).<\/li>\n<\/ul>\n<p>There were 11 children in the DTG arm with virological or clinical failure by 96 weeks (26%) vs 21 (49%) in standard-of-care; 8 (19%) vs 16 (37%) failures were virological. Of 6 deaths, 2 (5%) were in the DTG and 4 (9%) in the standard-of-care arms.<\/p>\n<p>The investigators found that there was less probability of failing in the DTG vs standard-of-care arm, p=0.05.<\/p>\n<p>For the difference in proportion with virological or clinical failure by 96 weeks &lt;14 kg, the Bayesian analysis gave an 11% difference in favour of DTG: -0.106 (95% CI -0.192 to -0.020). The other analyses also favoured DTG vs standard-of-care: stand-alone -0.196 (95% CI -0.379 to -0.005) and pooled -0.094 (95% CI -0.146 to -0.038). Test of heterogeneity of treatment effect between <u>&gt;<\/u>14kg and &lt;14kg: p=0.24.<\/p>\n<p>At 96 weeks, 76% of children in the DTG arm had viral load &lt;50 copies\/mL compared with 50% in standard-of-care, p=0.02. The corresponding proportions with cut-off &lt;400 copies\/mL were 91% vs. 71%, p=0.03.<\/p>\n<p>At 48 weeks, these proportions were 44% and 49% for &lt;50 copies\/mL, p=0.69. And 74% vs 69% for &lt;400 copies\/mL, p=0.69.<\/p>\n<p>There were a total of 34 serious adverse events: 15 (11 children) in the DTG arm vs 19 (11 children) in standard of care, p=0.92. This included the 2 vs 4 deaths. And 36 (19 children) had grade 3 and above adverse events in DTG vs 34 (21 children) in standard-of-care, p=0.79. There were 2 ART-modifying events in the standard-of-care arm: 1 raised liver enzymes and 1 vomiting.<\/p>\n<p>At 96 weeks there was a significant difference in mean change in total cholesterol (mg\/dL) from baseline in children &lt;14 kg also favoring DTG: -26 (95% CI -42 to -9), p=0.003.<\/p>\n<p>Presenting author, Pauline Amuge from Uganda, noted that these results support WHO guidelines and roll-out of DTG-based regimens for younger children starting first- or second-line ART and she added: \u201cprocurement of dispersible DTG for children &lt;20 kg should be expedited\u201d.<\/p>\n<h3>comment<\/h3>\n<p><strong>These results provide good evidence for rapid global rollout of DTG for children aged four weeks and above using the new dispersible 10 mg tablets. [3]\u00a0<\/strong><\/p>\n<p><strong>Following this ODYSSEY late breaker, WHO released a statement. [4] This applauded the results and emphasised the grim reality that children living with HIV still continue to be left behind by the global HIV response. <\/strong><\/p>\n<p><strong>In 2020, only 54% of the 1.7 million children living with HIV received ART compared to 74% of adults. Among WHO focus countries, only 40% of children (or 74% of children receiving ART) achieved viral suppression. <\/strong><\/p>\n<p><strong>WHO has recommended DTG-based ART for all infants and children since 2018 and provided dosing recommendations for those over four weeks old and weighing more than 3 kg in July 2020. <\/strong><\/p>\n<p><strong>New WHO 2021 consolidated guidelines on HIV [5] and the newly released policy brief on transitioning to the 2021 optimal formulary for antiretroviral drugs for children [6] give further guidance on how to transition to DTG-containing regimens as well as how to best dose it when co-treatment for TB is needed.<\/strong><\/p>\n<p><strong>Two generic formulations of DTG 10 mg dispersible tablets have been tentatively approved by the US FDA. [3] The cost for children in low- and middle-income countries where these are available is $4.50 for a 90-tablet bottle.\u00a0\u00a0<\/strong><\/p>\n<p>References<\/p>\n<ol>\n<li>Amuge P et al Dolutegravir-based ART is superior to standard of care in young children living with HIV. 13th International Workshop on HIV Paediatrics 2021(virtual workshop).16\u201317 July 2021. Late breaker oral abstract 124.<\/li>\n<li>Clayden P. Dolutegravir superior to standard of care in children and adolescents: results from the ODYSSEY trial. 1 June 2021.<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/40697\">https:\/\/i-base.info\/htb\/40697<\/a><\/li>\n<li>Clayden P. New formulation of dolutegravir will make modern ART available for babies and young children at less than $120 a year. 9 December 2020.<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/39465\">https:\/\/i-base.info\/htb\/39465<\/a><\/li>\n<li>WHO statement. New findings from the ODYSSEY trial confirm superiority of dolutegravir-based ART in young children. 16 July 2021.<br \/>\n<a href=\"https:\/\/www.who.int\/news\/item\/16-07-2021-new-findings-from-the-odyssey-trial-confirm-superiority-of-dolutegravir-based-art-in-young-children\">https:\/\/www.who.int\/news\/item\/16-07-2021-new-findings-from-the-odyssey-trial-confirm-superiority-of-dolutegravir-based-art-in-young-children.<\/a><\/li>\n<li>WHO. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. 16 July 2021.<br \/>\n<a href=\"https:\/\/www.who.int\/publications\/i\/item\/9789240031593\">https:\/\/www.who.int\/publications\/i\/item\/9789240031593<\/a><\/li>\n<li>WHO.\u00a0Transitioning to the 2021 optimal formulary for antiretroviral drugs for children: implementation considerations.16 July 2021.<br \/>\n<a href=\"https:\/\/www.who.int\/publications\/i\/item\/9789240031371\">https:\/\/www.who.int\/publications\/i\/item\/9789240031371<\/a><\/li>\n<\/ol>\n<p><em>This report was first posted on 17 July 2021.<\/em><\/p>\n\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Dolutegravir (DTG)-based ART was superior to standard-of-care in children weighing 3 to 14 kg, starting first- or second-line treatment. These 96 week results from the younger cohort of the ODYSSEY trial were presented at the 13th &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[314],"class_list":["post-40970","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-paediatric-workshop-2021"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/40970","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=40970"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/40970\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=40970"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=40970"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=40970"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}