New findings from the ODYSSEY trial confirm superiority of dolutegravir-based ART in younger children – A story by WHO

16 Jul, 2021

WHO welcomes new findings presented today at International Pediatric HIV Workshop on the superiority of dolutegravir (DTG)-based regimens in young children.

Children living with HIV continue to be left behind by the global AIDS response. In 2020, only 54% of the 1.7 million children living with HIV received antiretroviral therapy in 2020 compared to 74% among adults living with HIV. Among the focus countries, only 40% of children living with HIV (or 74% of children receiving antiretroviral therapy) achieved viral suppression in 2020.

The ODYSSEY trial, a multi-country randomised trial sponsored by Penta, has previously demonstrated superior treatment efficacy for DTG plus two nucleoside analogues versus standard-of-care (SOC) in 707 children ≥14kg (median age 12 years) starting first- or second-line ART. An additional cohort of 85 children <14kg, enrolled from Uganda, Zimbabwe and South Africa, completed 96 weeks follow-up on 28 June 2021.

Among these children, with the median age of 1.4 years, 28% had treatment failure by 96 weeks in the DTG arm vs 48% in the SOC arm. At 96 weeks, 77% of children in the DTG arm had VL<50copies/mL compared with 50% in SOC; corresponding proportions with VL<400copies/mL were 91% vs. 71%. Overall, DTG-based ART was superior to SOC (predominantly protease inhibitor-based ART) in young children starting first or second-line therapy, judged on treatment failure by 96 weeks. The treatment benefit for DTG in the <14kg cohort was consistent with that observed in children enrolled ≥14kg. There were no safety concerns on DTG.

WHO has recommended DTG-based HIV treatment for all infants and children since 2018 (1) and provided dosing recommendations for infants and children over four weeks of age and more than 3kg in July 2020 (2). Upcoming WHO 2021 consolidated guidelines on HIV (3) and the newly released policy brief on transitioning to the 2021 optimal formulary for antiretroviral drugs for children (4) provide further guidance on how to transition DTG-containing regimens as well as how to best dose it when treatment for tuberculosis is required.

Two generic formulations of DTG 10 mg dispersible tablets have been approved by the United States Federal Drug Administration (US FDA). This approval was swiftly followed by the announcement on World AIDS Day of a ground-breaking agreement negotiated by Unitaid and the Clinton Health Access Initiative that reduces the cost of HIV treatment by 75% for children in low- and middle-income countries where the DTG 10 mg dispersible tablet will be available at a cost of $4.50 for a 90-count bottle.

These new findings from the ODYSSEY trial confirm that DTG-based regimens can significantly improve virological suppression in young children and country programmes are encouraged to plan a rapid introduction of DTG-containing HIV treatment as the preferred first-line regimen for all infants and children who are as young as four weeks of age and weighing more than 3kg.

“The strong collaboration between paediatric HIV research networks is one of the elements that makes Paediatric DTG a success story from which we can all learn,” said Dr Meg Doherty, Director the WHO Global HIV, Hepatitis and STI Programmes. “These new findings from the ODYSSEY trial confirm once and for all the superiority of DTG-based regimens compared to existing regimens. We have a moral imperative to ensure that children are not denied this better regimen available in child-friendly formulations: country programmes have the tools to ensure sustained viral suppression for children.”

“We are delighted to share ODYSSEY trial results from clinical centres in Uganda, Zimbabwe and South Africa, demonstrating that dolutegravir is superior to other HIV treatment for infants and young children,” said Professor Diana Gibb one of Odyssey’s principal investigators. “These results provide strong evidence for rapid global rollout of dolutegravir for children aged four weeks and above using new dispersible baby tablets.”

WHO and partners are committed to supporting national governments as they develop rapid transition plans to DTG-based treatments, change policies and guidelines, quantify their needs, budget for and procure the appropriate stocks of medicines, organize distribution, train health care workers and sensitize and engage affected communities to ensure demand, treatment literacy for caregivers and children and smooth uptake of these new formulations.

The ODYSSEY trial is sponsored by the Penta Foundation and coordinated by the MRC Clinical Trials Unit at UCL, as well as INSERM, PHPT and HIV-NAT. 89% children in this global trial were enrolled from Africa, including all children weighing <14kg.

The trial was funded by ViiV Healthcare and the Penta Foundation. ODYSSEY took place in Uganda, Zimbabwe, South Africa, Thailand, and participating Penta centres in Germany, UK, Portugal, Spain.

(1): WHO. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV Interim guidance. 1 December 2018

(2): WHO. Considerations for introducing new antiretroviral drug formulations for children. Policy brief. 1 July 2020

(3): WHO. Consolidated guidelines on HIV prevention, testing, treatment, and service delivery. 16 July 2021

(4): WHO. Transitioning to the 2021 optimal formulary for antiretroviral drugs for children: implementation considerations – 16 July 2021