A once-a-day antiretroviral drug that is inexpensive and easy for children to take is also more effective at suppressing HIV than standard treatments, according to a global trial led by researchers at UCL (University College London).
The study, published today in New England Journal of Medicine, found that dolutegravir-based regimens, which are already widely used to treat adults, reduced the chances of treatment failure among adolescents aged three to 18 years by about 40% compared to standard treatments.
The results were based on a randomized controlled trial called ODYSSEY, which involved more than 700 children from 29 clinical centers in Africa, Europe and Asia, who were randomly given either dolutegravir or standard anti-HIV drugs, and who were followed up in at least two more year.
The results of the trial, which was sponsored by the Penta Foundation and funded by ViiV Healthcare, provided a new guideline from the World Health Organization recommending the use of dolutegravir-based treatment for children.
Professor Diana Gibb (MRC Clinical Trials Unit at UCL), lead researcher on the ODYSSEY study and one of the lead authors of the paper, said: “Our results provide strong evidence for the global rollout of dolutegravir for children with HIV.
“Medical treatments for children often lag behind adult treatments because of the separate formulations and studies needed. With the evidence from ODYSSEY, which used simplified dosing, this treatment gap has been reduced and we hope countries can quickly scale up children’s access. for treatment globally. “
Main author Dr. Anna Turkova (MRC Clinical Trials Unit at UCL) said: “About 1.8 million children live with HIV, but they have had limited treatment options with drugs that taste unpleasant, that need to be taken twice a day, or that come in. Large. pills that are hard to swallow.
Dolutegravir is usually given in small tablets once a day and the baby pills can be spread in water, which means that it is much easier for young children to take. This is important to promote the uptake of the treatment and adherence to it over many years. “Unfortunately, only about half of children living with HIV are currently receiving treatment, and those who are not being treated face high risks of impaired immunity and deteriorating health.”
In the study, the researchers found that 14% of children who received dolutegravir experienced treatment failure over two years compared to 22% of children who received standard treatment. Treatment failure was estimated to occur if the virus became measurable in the blood – ie. it was not completely suppressed – or if the child had symptoms of HIV-related ill health. Such an error may be a result of the drug not being taken and the drug not working.
Evidence from adults shows that dolutegravir has a high genetic barrier to resistance, meaning that viruses are less likely to become resistant to it over time. This was repeated in the ODYSSEY study, where there was much less resistance among children and adolescents to dolutegravir-based treatment.
Previous studies have suggested that dolutegravir may be associated with weight gain in adults, but the researchers said the new results were reassuring for children, where those who received dolutegravir gained 1 kg more and grew 1 cm taller over two years – both indicates better growth rather than abnormal weight gain. Children in the dolutegravir arm had better lipid profiles, which means lower risk of cardiovascular disease in the long term.
In the main trial, the children all weighed over 14 kg, and most were six years and over. The efficacy of the treatment was also studied among young children and infants weighing less than 14 kg, enrolled as a separate group in the trial; results have not yet been published.
The trial participants were enrolled in Uganda, Zimbabwe, South Africa, Thailand, the United Kingdom, Spain, Portugal, and Germany. Most of the participants were based in sub-Saharan Africa, where most children living with HIV are.
Previous results from the ODYSSEY study showed that children weighing 20 kg or more could safely take adult-strength dolutegravir tablets, inform the WHO about dosing guidelines and contribute to new licenses for the drug in the US and Europe during 2020.
Dr. Cissy Kityo, from the Joint Clinical Research Center in Uganda, the country that enrolls the most children in ODYSSEY, said: “It is crucial to simplify dosing. Larger children who can take the same tablets as adults immediately open access to dolutegravir for the most part of children living with HIV. It greatly simplifies procurement for national health systems in low- and middle-income countries and lowers costs. “
Dolutegravir is an integrase inhibitor – that is, it suppresses HIV by inhibiting integrase, an enzyme that the virus needs to replicate.
Reference: “Odyssey: Dolutegravir for first- and second-line HIV treatment in children” December 29, 2021, New England Journal of Medicine.