Africa: New Delivery, New Hope – Dolutegravir Oral Film Study Changes in HIV Prevention and Treatment for Babies

In the fight against HIV, one of the most vulnerable populations is often overlooked – newborn babies

It is estimated that 120,000 new HIV infections occur in children aged 14 years and younger every year, and more than 1.3 million children live with HIV, according to the Joint United Nations Programme on HIV and AIDS (UNAIDS), the main advocate for accelerated, comprehensive, and coordinated global action on the HIV/AIDS epidemic. Most of these children are born in resource-limited settings, where they face higher risks of mortality and morbidity common in such regions.

However, there was a remarkable reduction in the number of babies born with HIV over the past decade. This was mainly achieved through effective antiretroviral treatment provided to pregnant and breastfeeding women living with HIV.

Stellenbosch University’s Professor Adrie Bekker, a neonatologist at Tygerberg Hospital in Cape Town, South Africa, is at the forefront of efforts to improve HIV prevention and treatment for newborns. She has over two decades of experience in pediatrics and infectious diseases and has dedicated her life to improving the lives of newborns affected by HIV and other infectious diseases.

“I have been deeply drawn to the maternal-baby bond that exists after birth,” said Dr. Bekker. “What struck me was the lack of medications available to treat infections in babies, inspiring me to explore safe and effective dosing strategies for existing medications.”

Dr. Bekker’s journey into neonatology began in 2000 when she first started working with children. She qualified as a neonatologist in 2008 working at Tygerberg Hospital, where she developed an interest in HIV, tuberculosis, and bacterial infections.

One of her goals was to explore safe and effective ways to administer existing medications to newborns.

The study

Dr. Bekker is the co-principal investigator of the PETITE-DTG study, alongside Dr. Tim R. Cressey, a clinical pharmacologist, from the University of Chiang Mai in Thailand. This study is one of several performed under the Unitaid-funded BENEFIT Kids project, which aims to optimize treatment for children with HIV or multidrug-resistant tuberculosis. Their latest research focuses on an innovative drug delivery method – an oral dispersible film of dolutegravir- that could transform neonatal HIV prevention and treatment.

The PETITE-DTG study has determined the appropriate dosing of dolutegravir (DTG) for neonates under 28 days old born to women living with HIV, marking a significant advancement in neonatal HIV prevention and treatment. The study evaluated 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 at Tygerberg Hospital were administered DTG every 48 hours from birth to Day 14, followed by daily doses until four weeks of age. The results confirmed the regimen was safe, effective, and highly acceptable to mothers, with the DTG-Film being particularly easy to administer.

The study addressed a critical gap in neonatal HIV care, as DTG, a World Health Organization-recommended drug, had no prior dosing guidance for babies in the first four weeks of their lives (neonates). The findings pave the way for broader implementation of DTG in neonatal HIV prevention and treatment, potentially improving outcomes for infants born to HIV-positive mothers.

A breakthrough in drug delivery

Infants born to mothers with HIV need antiretroviral (ARV) medications for prevention or treatment. However, ARV options often rely on older liquid formulations, which can be difficult to administer, and may require refrigeration. Traditionally, HIV therapy for newborns relied on syrups, which presented several drawbacks, including poor taste and frequent stock shortages.

Some medicines require refrigeration, and since newborns comprise a small segment of the commercial market, there may be a shortage.

Dolutegravir is a game-changing HIV therapy for prevention and treatment

“In response, the WHO recently recommended switching to dispersible tablets, which have a longer shelf life,” she said. “The oral film is a new drug formulation being tested for the first time in babies. It’s small, thin (15mm x 25mm), taste-masked (mint-flavored), and dissolves quickly on the baby’s tongue. Mothers in our study preferred it because it ensures the baby receives the full dose, unlike the solution with dispersible tablets, which can spill during administration.”

The film offers a more efficient and user-friendly alternative to dispersible tablets, which require water and are administered by cup or syringe, which increases spillage risk and incomplete dosing. However, the film is not yet available for purchase.

“It has been manufactured and gone through the necessary processes, but is not yet available to be purchased,” Dr. Bekker said.

This study is the first to test its use in babies. In South Africa, children under five receive free HIV treatment, including dispersible tablets, but the film is not yet part of the program.”

This study aims to develop a dosing strategy to give newborns access to the most potent and safe drugs, improving their treatment outcomes.

Delays in developing suitable pediatric formulations of HIV drugs are a persistent issue.

Children often lag behind adults when it comes to accessing new drugs.

Dr. Bekker said that children typically face delays in accessing new medications because child-friendly formulations and safety studies are required. However, since the release of the 5 mg dispersible Dolutegravir tablet in 2020, progress has accelerated, and researchers are now investigating its potential use in newborns.

Since the current five-milligram DTG formulation was designed for children rather than newborns, it requires careful administration. “For the first two weeks of life, we give one tablet every second day before switching to daily dosing to avoid dangerously high drug concentrations,” she said. “This can be difficult for new mothers to remember, so the research team has introduced diary cards  to help remind the mothers.”

Dr. Bekker said that there were no major unexpected findings. However, they carefully studied the safety, since the drug was developed for children, not babies, but no safety issues were observed.

The impact of funding cuts

The Petite-DTG team’s work comes at a critical time, as global funding cuts threaten to undermine progress in HIV treatment and prevention. “It’s really concerning because every day you hear something about funding cuts,” she said. “It feels as if we’re going backward after making so much progress.”

Disruptions in U.S. funding for HIV care pose a significant threat to the health and well-being of children in Africa where many rely on these resources for essential services. The abrupt cessation of funding, primarily through the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), has already led to the suspension of critical programs that support vulnerable populations, including orphaned children living with HIV.

In 2003, the U.S. government, under President George W. Bush, established PEPFAR. USAID, the primary agency responsible for U.S. international development assistance, allocated and managed the initiative’s funding. More than 25 million lives have been saved worldwide through this ground-breaking scheme that allows some of the world’s poorest people to access anti-retroviral drugs (ARVs).

Africa greatly benefited from the efforts of the USAID and PEPFAR.

Experts warn, however, that funding cuts could have dire consequences, potentially leading to hundreds of thousands of additional deaths on the continent.

Dr. Bekker said that the cuts will impact the entire HIV program, including access for pregnant women and newborns. “With approximately 1.2 million HIV-positive pregnant women giving birth each year globally, these cuts will inevitably affect prevention and treatment efforts for newborns,” she said.

She expressed deep concern about the ongoing funding cuts, saying that the constant news of reductions is alarming and paints a bleak picture for the near future. She admitted that the uncertainty surrounding the situation is causing widespread worry, as it remains unclear what will happen next. She questioned whether other countries or organizations might step in to provide support, especially given the reports of HIV programs being shut down and life-saving medications failing to reach those in need.

Dr. Bekker said that these developments feel like a step backward, undoing the significant progress made in combating the HIV pandemic in recent years.

Beyond DTG

Long-acting antiretroviral medicines represent groundbreaking advancements in antiretroviral therapies in adults and children for HIV treatment and prevention, offering simplified dosing schedules that significantly improve adherence and treatment outcomes. Together, these therapies address common challenges such as daily pill fatigue and adherence issues, while offering innovative solutions for patients with complex treatment needs. Their success marks a transformative shift in HIV care, providing more convenient and effective options for diverse populations and paving the way for improved global health outcomes in the fight against HIV/AIDS.

Dr. Bekker said that long-acting antiretroviral treatments are promising, but dosing may be complicated as a baby grows very quickly and has many physiological changes after birth. However, if newborns could receive a single injection at birth, and again at a late stage during breastfeeding, to protect them from HIV for several months, prevention may be simplified.

“Imagine a baby is born to a mother with HIV, and you can just give one injection at birth, similar to the vitamin K injection (a shot given to newborns to prevent bleeding problems). You can potentially protect that baby for a couple of months against HIV, without the mom even having to give a tablet, syrup, or film,” she said.

Dr. Bekker stressed the need for continued investment in HIV research, particularly for vulnerable populations like babies in the first four weeks of their lives.

“I would like to make a plea that they don’t forget about neonates when they think of HIV prevention and treatment. I think neonates, similarly to pregnant women, often stand last in line for medications and HIV care. And I know they are a difficult population to study – that’s why people often shy away from it. But if we can make sure that these most vulnerable populations also get the best HIV care possible, we should try our best to see if we can get that right.”