South African approval of 4-in-1 combination ARV treatment for children a global first

Easy-to-administer treatment is an important step forward in the availability of optimal treatment options for infants and children living with HIV

14 Jun 2022

Viewpoint by
Dr Irene Mukui, Head of Disease, HIV, DNDi
Carol Ruffell, Director, DNDi GARDP Southern Africa

We are excited to announce that the South African Health Products Regulatory Authority has approved a 4-in-1 fixed-dose combination treatment for children living with HIV, developed by DNDi and Cipla Limited.

The 4-in-1 is a sweet-tasting combination of the four antiretrovirals (ARVs) abacavir, lamivudine, lopinavir, and ritonavir. The active ingredients are contained in strawberry-flavoured granules that can be sprinkled on breast milk, formula, or other age-appropriate foods. This makes the 4-in-1 a significant improvement over the lopinavir/ritonavir syrup that is bitter-tasting, has to be administered together with other separate formulations, and requires refrigeration. We expect the 4-in-1 to also be useful for children who have difficulties swallowing the tablet or pellet formulations.

We celebrate South Africa’s leading role as the first country globally to grant the 4-in-1 regulatory approval. Interventions to prevent mother-to-child transmission have significantly reduced the number of children living with HIV in South Africa but approximately 2% of babies born to mothers living with the disease will contract it in utero, during birth, or in their first year of life. Around 238,000 children below the age of 15 in South Africa are living with HIV. Just over half are on treatment.

The approval of the 4-in-1 represents an important step forward in the availability of optimal treatment options for infants and children living with HIV. It is our hope that similar approvals will be seen in other countries that have a high burden of disease among children.

Although there has been significant improvement in the availability of newer and better drugs for children living with HIV in recent years, drug development for children typically lags far behind the development of drugs for adults, largely due to the challenges of conducting clinical trials that include children. Clinical trials including infants and young children conducted by DNDi and partners in Uganda concluded that the 4-in-1 is effective, easy for caregivers to administer, and adapted to use in resource-constrained settings as it does not require refrigeration and has a 24-month shelf-life. It is suitable for infants and children weighing between 3 and 25kg.

We would like to take this opportunity to thank our pharmaceutical partner, Cipla, for its dedication to the development of this treatment and to obtaining regulatory approval for its use. We would also like to thank our funders, particularly Unitaid and the French Development Agency, our research partners, and the investigators, doctors, nurses, caregivers, and children who enabled the achievement of this important milestone. It is a breakthrough for paediatric research in African countries.

As we celebrate this achievement, DNDi is actively preparing to facilitate access to the 4-in-1, which will complement other child-friendly HIV treatment options that have been introduced recently, including paediatric dolutegravir-based regimens.