San Francisco — The PETITE-DTG study evaluated dolutegravir (DTG) — a drug that revolutionized HIV treatment in adults and children — in infants less than 28 days old, using a pediatric 5 mg dispersible tablet (DTG-DT) and a novel 5 mg oral dispersible Film (DTG-Film).
New research has determined the appropriate dosing of a key treatment for neonates (aged <28 days) born to women living with HIV. The study, presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI), is a significant advancement in HIV treatment (please see the study abstract below).
Neonates require potent antiretroviral drugs (ARVs) against HIV but there are fewer drugs available for children compared to adults. Administering the correct neonatal dose of ARVs can be challenging due to rapid body weight changes and physiological developments in early life. Therefore, it remains a priority to generate dosing and safety information for the newest ARVs in neonates.
Dolutegravir is recommended by the World Health Organization (WHO) for children and adults living with HIV. Since its approval in 2013, DTG has emerged as a more effective and cost-efficient alternative to older ARV regimens. Currently, DTG is used to treat more than 22 million people in 110 low- and middle-income countries but no DTG dosing guidance had been available for neonates.
Recognizing this critical gap, the World Health Organization (WHO) Paediatric Antiretroviral Drug Optimization (PADO) group prioritized neonatal DTG dosing as an urgent research need to be addressed. In response, the PETITE-DTG study — funded by Unitaid under the BENEFIT-KIDS project — was launched to assess the safety and pharmacokinetics (PK) of DTG in neonates (≥2 kg birth weight) born to mothers on DTG-based treatment.
The PETITE-DTG study was conducted through the newly established PETITE PLATFORM. This platform is a research collaboration between Dr. Adrie Bekker at Stellenbosch University in South Africa and Dr. Tim. R. Cressey at Chiang Mai University in Thailand, and is dedicated to expediting use of latest pediatric ARVs to neonates through safety and PK studies.
Dr. Cressey said, “The PETITE PLATFORM is helping to accelerate the development of neonatal dosing recommendations for ARV drugs. Our goal is to ensure that newborn babies can also benefit from the latest advancements in HIV care”.
The PETITE-DTG study assessed two pediatric DTG formulations, a 5 mg dispersible tablet (DTG-DT) and a novel 5 mg oral dispersible film (DTG-Film). Forty-one term neonates were enrolled at Tygerberg Hospital and administered DTG-DT or DTG-Film for HIV prevention. The dosing regimen consisted of 5 mg DTG every 48 hours from birth to Day 14 of life, followed by 5 mg every day until four weeks of age. The results demonstrated that this DTG dosing strategy was safe, acceptable and maintained efficacious drug levels.
Dr. Bekker said, “It is exciting that these data will support for the first time the use of dolutegravir in neonates. This dosing strategy can now be rapidly implemented across different settings due to the widespread availability of pediatric DTG.”
Both DTG formulations were successfully administered, with solid formulations preferred over syrups. Of note, this was the first evaluation of an ARV oral film in neonates, administered by placing the film directly on the tongue. Despite being a new experience, mothers found this method highly acceptable.
Dr. Lario Viljoen of Stellenbosch University said, “It has been encouraging to see how mothers engage with these novel formulations; we observed high levels of acceptability across the trial. With appropriate messaging and support, these findings can be used to inform future care for infants.”
One mother who participated in the trial along with her infant son said, “As soon as I put [the DTG-Film] on his tongue … it just dissolves in a few seconds, he enjoys it.”
A second mother noted, “[DTG-DT] has been manageable… it dissolves quickly, and then I give it to [my baby]… she does like it, it smells nice”
The pediatric DTG formulations were kindly donated to the PETITE-DTG study by Viatris Ltd. (DTG-DT) and Laurus Labs Ltd. (DTG-Film).
Adapting current and novel pediatric ARVs — as done in the PETITE-DTG study — strengthens efforts to improve HIV prevention and treatment options for neonates, potentially leading to better outcomes. According to UNAIDS, new HIV infections among children declined by 62% between 2010 and 2023, partly reflecting the impact of enhanced treatment strategies.
Additional PETITE research presented at CROI 2025 explored the alignment of abacavir/lamivudine (ABC/3TC) dosing with DTG in neonates, which paves the way for harmonized neonatal ARV dosing strategies.
The four abstracts presented at CROI 2025 include:
Abstract # Title #122 Multi-Dose PK/Safety of Dolutegravir Dispersible Tablets & Oral Films in Neonates: PETITE-DTG Study #1044 Maternal Antiretroviral Formulation Preferences for Neonates #1045 Acceptability of a Dolutegravir Dispersible Tablet and a Novel Oral Film Formulation in Neonates #1048 Alternative Dosing of ABC/3TC Dispersible Tablets to Align with Dolutegravir Dosing in Neonates
Overall, these findings provide essential evidence to support DTG extension to neonates, closing a key knowledge gap.
“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,” says Cherise Scott, Senior Technical Manager at Unitaid. “We will not allow children to be neglected in global health responses simply because their needs are more complex.”
