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.

Dolutegravir is recommended by the World Health Organization (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 2 kilograms and born to mothers receiving dolutegravir-based HIV treatment, were enrolled in the study at Tygerberg Hospital to test two peadiatric formulations of dolutegravir.

The first method involved using a 5 milligram dispersible tablet dissolved in 5 milliliters of water and given every second day for the first 14 days of life, then once daily until the baby was four weeks old. This was administered with a syringe.

The second method involved using a novel 5 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 milligram of dolutegravir twice daily.

The study’s findings were presented at the Conference on Retroviruses and Opportunistic Infections in March. Researchers are currently 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.

In examining dosing safety and efficacy, she says that 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. Bekker explains that 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 notes it is 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 says pointing out a video clip on her desktop of a film strip being placed in a tiny baby’s mouth.

Bekker says the colourless dolutegravir film is made by the Indian multinational pharmaceutical company Laurus Labs. Previously, it had only been tested in adults and 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,” she says.

She says the research findings have been presented to the World Health Organization (WHO) and expects they will be included in the organisation’s upcoming updated dosing guidelines for infants and children.

Commenting on dolutegravir for neonates, Bekker says: “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 adds: “The generic 10 milligram dolutegravir scored dispersible tablet is already available and being used in children. What we’ve shown now is that 5 milligram of dolutegravir with this dosing strategy is safe for neonates…The 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.”

“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,” says 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 says 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 using 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 5 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…”

While the study focused on healthy full-term babies weighing at least two kilograms, Nuttall noted that many babies born to mothers living with HIV are either premature or have 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 says. “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 notes that the WHO-led Paediatric Drug Optimisation group identified long-acting cabotegravir injectables as a high research priority for HIV prevention in neonates. She adds 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, amongst others, funds research and helps facilitate the more rapid introduction of new health technologies.

This article first appeared on Spotlight. Read the original article here.

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