Easy-to-take medicine better at suppressing HIV in children
30 Dec 2021
A once-a-day antiretroviral medicine that is low-cost and easy for children to take is better at suppressing HIV than standard treatments, according to a global trial led by researchers at MRC CTU at UCL.
The study, published yesterday in The New England Journal of Medicine, found that dolutegravir-based regimens, which are already widely used to treat adults, reduced the chance of treatment failure among children and adolescents, aged three to 18, by around 40% compared to standard treatments.
The findings were based on a randomised controlled trial called ODYSSEY involving more than 700 children from 29 clinical centres in Africa, Europe and Asia. Children were randomly given either dolutegravir-based treatment or standard anti-HIV drugs and were followed up for at least two years.
The findings from the trial strengthened the World Health Organisation recommendations to use dolutegravir-based treatment as preferred treatment for children.
In the study, researchers found that just over 1 in 7 (14%) of children receiving dolutegravir experienced treatment failure over two years compared to just over 1 in 5 (22%) of children receiving standard treatment. Treatment failure was defined if the virus became measurable in the blood – ie it was not fully suppressed – or if the child had symptoms of HIV-related ill health. Such a failure may be a result of the drug not being taken as well as the drug not working.
ODYSSEY has also showed that dolutegravir is better in stopping resistance compared to other used treatments, which is in line with the findings from adult trials. This means that dolutegravir preserves activity of companion drugs and protects them from becoming inactive due to emergent drug resistance.
Past studies have suggested dolutegravir may be linked to weight gain among adults. However, in ODYSSEY children on dolutegravir were only 1kg heavier than the children in the standard of care group at 2 years after starting antiretrovirals, with the difference appearing within the first year after starting treatment and not increasing over time. At the same time children receiving dolutegravir were nearly 1cm taller at 2 years, suggesting the changes are likely due to normal growth. They also had better blood fat results meaning their risk of heart problems in adulthood may be lower.
In the main trial the children all weighed over 14kg and most were aged six and over. Children weighing under 14kg were enrolled in a separate group, and the preliminary results were similar to the older children in the main trial, showing that dolutegravir-based treatment works better than non-dolutegravir antiretroviral regimens in this group too (the full results are yet to be published).
The trial participants were enrolled in Uganda, Zimbabwe, South Africa, Thailand, the UK, Spain, Portugal and Germany. Most of the participants were based in sub-Saharan Africa, where most children living with HIV are.
Earlier findings from the ODYSSEY trial showed that children weighing 20kg or more could safely take adult-strength tablets of dolutegravir, informing WHO dosing guidance and contributing to new licences for the drug in the United States and Europe during 2020.
The ODYSSEY trial was sponsored by the PENTA Foundation and funded by Viiv Healthcare.