1. What is dolutegravir?
Dolutegravir (DTG) is the World Health Organisation’s (WHO) recommended first-line drug to treat HIV. It is more effective, easier to take, has fewer side effects than alternatives, and has a high genetic barrier to developing drug resistance. In 2013, DTG was approved for adult use in most high-income countries and quickly became one of the most widely prescribed treatments for HIV.
Understanding that it could take up to 10 years for low- and middle-income countries (LMICs) to access this revolutionary treatment, the global health community, including Unitaid and CHAI, came together to successfully overcome the barriers. As a result, a generic, affordable formulation of DTG for adults was rolled out in Africa in 2017.
In 2018, the WHO extended the recommendation for DTG as the preferred first-line treatment to all children over the age of four weeks and 3kg. However, only children weighing 20kg or more have been able to access the medication so far, due to a lack of affordable age-appropriate formulations for younger children.
“UNAIDS is excited that optimal Dolutegravir-based HIV treatment is now affordable and in a palatable form for almost all but the very youngest children. We call on countries, donors and implementing partners to place orders for this life-saving treatment,” said Winnie Byanyima, UNAIDS Executive Director. “More palatable and effective HIV treatment is critical for children to stay healthy and remain on treatment. But currently, just over half (53%) of all children living with HIV globally have been diagnosed and are on HIV treatment, two thirds of the missing children are aged 5-14. That is unacceptable. We must urgently scale up efforts to find and treat all of the missing children living with HIV.”
2. Why is this paediatric DTG formulation a game-changer?
Quite simply, this formulation enables the most effective, age-appropriate anti-retroviral medication available to be administered to children living with HIV.
Babies and young children who are HIV positive are at the highest risk of dying without treatment. Around 80,000 infants and toddlers die each year as a result of AIDS.
The lack of options when it comes to effective drugs and formulations has made treating paediatric HIV challenging. The current choices include syrups that are unpalatable and require cold chain storage, and solid formulations that are extremely bitter, hard to swallow and have to be taken multiple times per day.
These barriers have compromised adherence to treatment, resulting in poor outcomes in children and significant premature death. The new DTG 10mg dispersible formulation – when coupled with other available dispersible ART treatments – provides treatment that is easy to administer, tastes good, has reduced side effects, and can ultimately improve viral suppression for the youngest and most vulnerable children.
The new regulatory approval of the DTG 10mg dispersible tablet formulation will finally enable access to the preferred WHO treatment to all children living with HIV, transforming paediatric HIV treatment.
Photo: Giulio Donini/Unitaid
Sister Mary Owens is the executive director of Nyumbani, an organization dedicated to providing HIV/AIDS services to children and affected families in Kenya since 1991. She explains: “At last, what we have been waiting for since our adolescents accessed DTG - a DTG dispersible formulation for our babies and little children. Having watched these little children struggling to drink the bitter syrup and the older children trying to swallow several big bitter tablets, words are inadequate to express our relief for our little ones and our gratitude.”
3. This new agreement makes HIV treatment more affordable, meaning it will reach more children in low- and middle-income countries
The new pricing agreement with Viatris and Macleods will significantly lower the cost for yearly paediatric HIV treatment from over $480 per child for the current standard of care to under $120 per child for the full regimen.
Price has been a key factor in determining whether children living in resource-constrained environments can access optimal HIV treatment.
Buki Ayinde from HIV treatments advocates network AfroCAB says: “Our children have had the worst deal when it comes to HIV treatment. DTG 10mg is more easily and conveniently administered. Its availability will mean inclusion, convenience, better-tolerated medication and treatment outcomes for our babies and children.”
This 75% cost saving will also enable governments of LMICs to divert savings towards the provision of better paediatric HIV treatment services, including targeted interventions to find children who are currently not receiving treatment and at high risk of mortality.
4. The work on this formulation has created a new model for the expedited development of generic HIV drugs – so medication will reach those that need it faster
Research and development of ARV formulations for children has traditionally lagged behind their adult equivalents, with delays of up to a decade the norm.
The development of drugs for children is often only considered once pre-clinical Phase I and Phase II studies in adults are completed, which can take many years. Although regulatory frameworks in the United States and Europe have put in place measures to promote the development of drugs for children, the process has remained extremely lengthy.
This has been compounded by the shrinking market for drugs for children in high-income countries, where rates of HIV transmission are now extremely low, further reducing investment incentives for manufacturers.
Through an innovative partnership between Unitaid, CHAI, and ViiV Healthcare, together with Mylan (now a subsidiary of Viatris) and Macleods, regulatory approval for the generic paediatric DTG 10 mg dispersible tablets has taken approximately two years - a much quicker timeline than the historical ten years. This is also the fastest ever regulatory approval of a generic pediatric ARV formulation, following approval of the innovator product.
This formulation was made possible through a Medicines Patent Pool (MPP) licensing agreement, which allows generic manufacturers to produce low-cost versions of DTG for use in at least 95 countries for the adult formulation and 121 countries for the paediatric version.
MPP’s Executive Director Charles Gore explains: “With so many infants still infected at birth, it is imperative that these young lives have access to adapted, efficacious medicines early on. We will now actively work with our licensees Viatris and Macleods to ensure rapid scale-up.”
5. This new formulation paves the way for continued treatment improvement
There is significant work required at country level to ensure that the new formulation reaches children. Unitaid is partnering with CHAI, PEPFAR, The Global Fund, AfroCAB, EGPAF, WHO and other key stakeholders to ensure that children are able to have widespread access to DTG as quickly as possible.
The development partnership also serves as a model to accelerate access to other missing formulations for children living with HIV, including a fixed-dose combination of darunavir/ritonavir, but also across other disease areas where children continue to be left behind, such as tuberculosis.
New paediatric neonatal liquid formulations of dolutegravir to treat the smallest babies are being developed and are showing promising results when compared to dispersible paediatric tablets.
Unitaid’s Executive Director Philippe Duneton says: "Our mission is to provide solutions for underserved populations and the most vulnerable. Children living with HIV/AIDS are particularly underserved and vulnerable. That is why it so important and critical to have new life saving medicines adapted to them, and I’m grateful to partners, industry and regulators for making this possible.”