01-05-2025
Cape Town study brings hope to newborns left behind in HIV treatment advances
Two new ways of giving the important HIV medicine Dolutegravir to newborn babies have been found to be safe and effective, according to new research done in Cape Town.
The new findings support, for the first time, the broader use of Dolutegravir in infants who are less than 28 days old.
Spotlight met with the passionate clinician-scientist behind the research at her office in Cape Town.
Two new ways of giving the important HIV medicine Dolutegravir to newborn babies have been found to be safe and effective, according to new research done in Cape Town. The new findings support, for the first time, the broader use of Dolutegravir in infants who are less than 28 days old.
Dolutegravir is recommended by the World Health Organisation (WHO) for infants, children and adults and is the preferred HIV medicine in South Africa. It exists in a scored 10-milligram child-friendly dispersible tablet. But until now, there hasn't been any guidance on how to safely use it for newborns in their first four weeks of life.
A study called PETITE-DTG aimed to bridge this critical gap in neonatal HIV care.
Forty-one full-term babies, each weighing at least two kilogrammes and born to mothers receiving Dolutegravir-based HIV treatment, were enrolled in the study at Tygerberg Hospital to test two paediatric formulations of Dolutegravir.
The first method involved using a five-milligram dispersible tablet, dissolved in five millilitres of water and given every second day for the first 14 days of life, then once daily until the baby four weeks of age. This was administered with a syringe.
The second method involved using a novel five-milligram mint-flavoured film the size of a fingernail that dissolves on the tongue in seconds. It followed the same dosing schedule as the first method.
Findings showed that both formulations were safe and effective, achieving drug concentrations comparable to adults receiving 50 milligrams of Dolutegravir twice daily.
The study's findings were presented at the Conference on Retroviruses and Opportunistic Infections in March.
Researchers are writing up the final results of the study for publication in a peer-reviewed medical journal.
Professor Adrie Bekker, a neonatologist from the University of Stellenbosch is co-principal investigator of the PETITE-DTG study alongside Dr Tim Cressey, a clinical pharmacologist from the University of Chiang Mai in Thailand.
"The study results confirmed that the regimen (both five-milligram Dolutegravir formulations) was safe, effective, and highly acceptable to mothers, with the Dolutegravir film being particularly easy to administer," Bekker told Spotlight in her office at Stellenbosch University's medical campus next to Tygerberg Hospital.
In examining dosing safety and efficacy, she said the study found that both formulations "achieved target concentrations" in the neonates, without the newborn babies experiencing any adverse effects related to the medicine. All neonates were HIV negative at the end of the study.
Babies born to a mother living with HIV may need antiretroviral medicines for the prevention or treatment of HIV. According to Bekker, neonates are currently given an older type of liquid HIV medication that doesn't taste good, costs more than Dolutegravir, is harder to give properly, and can't be stored for long.
The novel film method was popular with mums in the study, who cited its simplicity of administering and dose accuracy as highly advantageous, with no risk of the medicine being spit out or other spillage.
"I wash and dry my hands and I cut the paper, it's quick. As soon as I put it on his tongue, it just dissolves in a few seconds, he enjoys it," said one mother, as quoted on a poster highlighting the results of the study.
Commenting on the film strip, Bekker noted it was one of the least disruptive ways to give medication.
"So what has been amazing to me is that the babies seem to be completely oblivious of what is happening when the mother puts the film in their mouth," she said, pointing out a video clip on her desktop of a film strip being placed in a tiny baby's mouth.
"If they were crying, they would just keep on crying. If they were sleeping, they would just keep on sleeping. If they were happy, they would just keep on being happy. It really is the most unintrusive way of administering medication."
According to Bekker, the colourless Dolutegravir film is made by the Indian multinational pharmaceutical company Laurus Labs. Previously, it had only been tested in adults and it is not yet commercially available. "It's actually never even been used in children…And so our study for the first time tested the Dolutegravir film in newborns to see what drug levels are found in a baby when you use it."
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She said the research findings were presented to the World Health Organisation (WHO) and they are expected to be included in the organisation's upcoming updated dosing guidelines for infants and children.
Commenting on Dolutegravir for neonates, Bekker said: "I think the first step is to actually get this recommendation into the WHO guidelines. As soon as the WHO releases their updated HIV guidelines, then countries can decide whether they want to adopt it or not."
Commenting on the availability and possible roll-out of Dolutegravir for neonates, she added: "The generic 10-milligram Dolutegravir scored dispersible tablet is already available and being used in children. What we've shown now is that five milligram of Dolutegravir with this dosing strategy is safe for film is a bit more complicated because it is not yet commercially available. And we don't know the price of the drug; all of that will need to be discussed and negotiated with the company and relevant parties before it can become available."
The PETITE-DTG research has been welcomed by fellow scientists.
"Adrie Bekker and her colleagues at Tygerberg Hospital and in Thailand have done great work and are really moving the field forward for neonatal antiretroviral treatment," said Associate Professor James Nuttall, a paediatric infectious diseases sub-specialist at the Red Cross War Memorial Children's Hospital and the University of Cape Town.
He said the research "provides really nice information about how we could use our existing drugs to treat neonates, potentially".
Nuttall described the new film as extraordinary, and suggested that it might eventually replace the current drug formulations.
For Nuttall though, making provision for use of a pill like the scored 10 milligram dispersible tablet that's already available and routinely used to treat children in South African hospitals is more immediately relevant.
"Using this five milligram dispersible tablet in neonates and working out the dosing schedule for that, that's the real advance of this study to me, the big win."
He anticipates these findings to be implemented in South Africa in the next few years. "From what I understand, she (Bekker)] has presented this to WHO already. And once it gets accepted and included into WHO guidelines, then countries tend to really take note and follow, that's when it makes its way into national guidelines…"
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While the study focused on healthy full-term babies weighing at least two kilogrammes, Nuttall noted that many babies born to mothers living with HIV were either premature or had a low birth weight.
"So this dosing and safety information doesn't yet apply to those children," he said.
Bekker already has her eye set on assessing dosing safety for pre-term newborns.
"So, obviously, our dream is to extend this to pre-term babies," she said.
"And there is a possibility that a 2.5-milligram Dolutegravir film may be a good dose for pre-term neonates. Obviously, that will have to be studied very rigorously first."
Other research goals include the hope of being involved in studies assessing long-acting antiretroviral drugs in neonates.
Bekker noted that the WHO-led Paediatric Drug Optimisation group identified long-acting Cabotegravir injectables as a high research priority for HIV prevention in neonates.
She added that developing patches with tiny microneedles that deliver HIV medication could hold great promise for treating newborns in the future.
Commenting on the PETITE-DTG study, Dr Moherndran Archary, who has been at the forefront of South Africa's HIV response for children, said: "Professor Bekker's research has directly impacted access to life-saving HIV medication for newborn infants – the most vulnerable of populations who have not traditionally benefited from the significant advances in HIV treatment."
The PETITE-DTG study is one of many under the Unitaid-funded BENEFIT Kids project aiming to improve treatment for children with HIV or multidrug-resistant tuberculosis.
UNITAID is a global health initiative that, among others, funds research and helps facilitate the more rapid introduction of new health technologies.
