In January 2022, a brand-new formulation of the leading HIV treatment, dolutegravir, was announced. Resembling a thin film about the size of a fingernail, it dissolves on the tongue and provides a new way to treat children with HIV. This medicine formulation could make an enormous difference in the lives of children living with HIV, but the drug had only been studied in healthy adults and tentatively approved in the United States.
One year later, the first baby in the world received the treatment in South Africa. And in early 2025, the results of the PETITE-DTG trial will be presented, potentially improving treatment for newborn babies – the only population still waiting for access to dolutegravir – as well as children of all ages.
Babies born to a mother living with HIV need antiretroviral medicines for prevention or treatment. Currently, they are treated with an older set of liquid formulations that are more expensive and complex to administer, requiring carers to use a syringe to measure specific volumes that often change as the baby grows. The medicines sometimes require refrigeration and, because newborns make up such a small segment of the commercial market, the medicines can suffer from stockouts.
Dolutegravir is a game-changing HIV treatment. It acts quickly, causes fewer side effects than alternatives, is inexpensive and exists in a dispersible, child-friendly tablet. But it is not currently recommended for newborn babies.
“We set out to evaluate existing pediatric formulations of dolutegravir in newborn babies to close the last evidence gap and improve treatment options for this vulnerable population.”
Dr. Adrie Bekker
Co-principal Investigator of the PETITE-DTG study
Dr. Adrie Bekker, from the University of Stellenbosch is co-principal investigator of the PETITE-DTG study alongside Dr. Tim Cressey from the University of Chiang Mai. The study is one of several under the Unitaid-funded BENEFIT Kids project, which aims to optimize treatment for children with HIV or multidrug-resistant tuberculosis.
Child medicine recommendations regularly exclude babies younger than 4 weeks old, and the additional research needed may lag years – or decades – after drugs are initially approved for adults and children. This deprives newborns of lifesaving products and can force health care workers to use medicines off label, without the understanding of safety and efficacy that comes from a regulatory study.
“We wanted to understand how to give dolutegravir to newborns so they wouldn’t be left behind. Then, we heard about the oral film, and we immediately recognized the immense value such a medicine formulation could have for all children, but particularly the smallest babies.”
Dr. Tim Cressey
Co-principal Investigator of the PETITE-DTG study
The dissolvable oral film contains the same dose of dolutegravir as the dispersible tablet but uses a novel delivery method that could respond to challenges caregivers face when giving medicines to children: the liquids can be spit out, leaving a parent unsure how much medicine the child has received.
The researchers moved quickly, leveraging the existing research collaboration, and amended the study protocol to study both formulations, the dispersible tablet and the oral film.
“Now we hope to be able to present evidence guiding the safety and dosing for dolutegravir at the same time as we share similar results into the oral film. This research won’t only benefit newborns – young children of all ages could benefit from such a formulation,” Dr. Cressey explains.
Dr. Lario Viljoen, the investigator leading the acceptability study into the oral film, recognizes that it may not be a medicine delivery method familiar to many parents: “We weren’t sure how caregivers would feel about this formulation. It doesn’t matter if the drug formulation is effective if mothers don’t want to give it to their children.”
But, although some caregivers expressed hesitancy at first, many seem to be won over after they use it for the first time. And the babies seem completely unaware of the medicine, which is flavor masked and dissolves in a few seconds.
“I did not experience any hardships using it,” says one mother. “I loved the film because it is easy to administer.”
The PETITE study is one of several investigations in the BENEFIT Kids project, which has been working to improve treatment for children affected by multidrug-resistant tuberculosis (MDR-TB) and HIV since 2019.
“The easier we can make it for a child to take their medicines regularly, the more likely it is that they will complete their treatment successfully. We will not allow children to be neglected in global health responses simply because their needs are more complex.”
Cherise Scott
Senior Technical Manager at Unitaid
The BENEFIT Kids project is just one example of Unitaid’s dedication to child medicines, making a major contribution to the otherwise neglected area of child TB. BENEFIT Kids has developed pediatric formulations of medicines that are key to second-line TB treatment, filled evidence gaps to understand appropriate dosing for children with TB and HIV at different ages, proven out cost-effective methods for MDR-TB treatment for children, and demonstrated the safety and effectiveness of the first-ever MDR-TB preventive regimen for children, which received the World Health Organization’s recommendation shortly thereafter.
As World Children’s Day, 20 November, highlight the rights of children, these trials add to Unitaid’s ongoing commitment to child health. Since its creation in 2006, Unitaid has prioritized children’s needs, helping ensure not only that children can access treatment, but that care is designed with them at the center.
Results of the PETITE-DTG study will be presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in March 2025. The trial used medicine formulations donated by Viatris Ltd (dolutegravir dispersible tablet) and Laurus Labs (dolutegravir oral film).
