2019 R&D portfolio in review: Paediatric HIV

 

DNDi aims to help end the neglect of paediatric HIV by developing optimal child-friendly antiretroviral formulations for children living with HIV, with a special focus on infants and young children who are at the highest risk of dying without treatment.

 

Young child looking at the camera in village in UgandaDNDi’s current paediatric HIV portfolio includes:

 

R&D development stage iconDevelopment

 

  • 4-in-1 (ABC/3TC/LPV/r): In October 2019, Cipla submitted the ‘4-in-1’ fixed-dose combination of abacavir, lamivudine, lopinavir, and ritonavir (ABC/3TC/LPV/r) to the US Food and Drug Administration (FDA) for tentative approval. In December, Cipla announced that this strawberry-flavoured HIV treatment will be priced at under one dollar a day for children weighing up to 14 kg.

    The 4-in-1 combines the protease inhibitors lopinavir and ritonavir (LPV/r) with the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine and abacavir in the form of granule-filled capsules. Developed for infants and young children weighing from 3 to 25 kg, parents and caregivers will be able to administer the drugs by opening the capsules and sprinkling the granules on soft food, water, or milk. The 4-in-1 does not require refrigeration and is a great improvement over the current option, a bitter-tasting syrup of LPV/r with high alcohol content that must be refrigerated.

    Currently, DNDi is running the LOLIPOP study in Uganda to provide clinical data on the 4-in-1 in infants and young children living with HIV. The first patient was enrolled in June 2019 at the Regional Referral Hospital in Mbarara, Uganda. The study will be key to assist scale-up of the product if tentative FDA approval is received.

 

R&D implementation stage iconImplementation

 

  • 2-in-1 LPV/r pellets and ABC/3TC: DNDi completed the LIVING study in Kenya, Uganda, and Tanzania, after enrolling over 1,000 children across 12 sites in Kenya, Uganda, and Tanzania.
  • Superbooster therapy paediatric HIV/TB: The drug rifampicin is the backbone of the regimen to treat tuberculosis (TB) in children. However, rifampicin reduces the bioavailability of protease inhibitors such as lopinavir/ritonavir (LPV/r), a major challenge in treating children infected with both HIV and TB. The results of an earlier DNDi study demonstrating the safety and effectiveness of ‘super-boosting’ (which involves adding extra ritonavir to the LPV/r regimen to counter this drug-drug interaction) strengthened the WHO recommendation to use super-boosting in HIV/TB co-infected children when they are on an LPV/r-based therapy.

    DNDi is now preparing to conduct a similar study to evaluate the 4-in-1 for treatment of young children co-infected with HIV and TB.

 

Photo credit: Karin Schermbrucker-Unicef/DNDi