R&D Portfolio Update February 2019: DNDi Paediatric HIV programme

 

DNDi aims to deliver:

  • A solid first-line “4-in-1” fixed-dose combination of abacavir/lamivudine/lopinavir/ritonavir for infants and young children under three years of age
  • Immediate introduction of the US FDA approved “2-in-1” LPV/r pellets, to replace high-alcohol syrups, before the availability of better-adapted 4-in-1 products.

 

Little boy with paediatric HIV being measured by a nurse in a hospitalDNDi’s current paediatric HIV portfolio includes:

 

Development

Development

Two projects in the development phase:

 

  • ‘4-in-1’ LPV/r/ABC/3TC: A first-line “4-in-1” fixed-dose combination of abacavir/lamivudine/ lopinavir/ritonavir (LPV/r/ABC/3TC) is on track to be submitted for registration in 2019. This 4-in-1 fixed-dose combination will be simple to use with water, milk, breast milk, and food. It will be taste-masked and heat-stable – a great improvement over the current option, a paediatric syrup of lopinavir/ritonavir (LPV/r) with high-alcohol content.

    To provide clinical data in young HIV-infected infants and children, DNDi is preparing a study, called LOLIPOP, to assess this 4-in-1 combination as an easy-to-use paediatric formulation in a Phase I/II study. The LOLIPOP study, which has received ethical approval, will begin in March 2019 in Uganda and will generate pharmacokinetic, safety, and acceptability data on the 4-in-1 to provide evidence for worldwide scale-up.

  • LPV/r pellets with dual NRTI: In September 2015, DNDi launched the LIVING study with five sites in Kenya to provide early access to lopinavir/ritonavir (LPV/r) “2-in-1” pellets, which are taken orally and are an improvement over the high-alcohol syrups that were previously the only available LPV/r formulation. The study was expanded to Uganda in May 2016, and Tanzania in 2017. As of December 2018, the LIVING study had enrolled 1,003 children across 12 sites in Kenya, Uganda, and Tanzania, and follow-up was completed for the Kenyan and Ugandan sites.

    In February 2018, interim results of the LIVING study were released, showing that 83% of the children in the study were virologically suppressed at 48 weeks with the 2-in-1, compared to 55% at the beginning of the study. These results show that the 2-in-1 is effective and well-tolerated by children.

    DNDi is actively preparing plans to support access to the 4-in-1, and transition from the interim 2-in-1 in sub-Saharan African countries once it is registered. 

 

Implementation

Implementation

One project in the implementation phase:

 

  • 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). This negative drug-drug interaction is a major challenge in treating children infected with both HIV and TB. As part of its development of protease inhibitor-based antiretroviral regimens, DNDi carried out a pharmacokinetic study in 96 infants and young children co-infected with HIV and TB at five sites in South Africa to demonstrate the safety and effectiveness of “super-boosting,” which involves adding extra ritonavir to the LPV/r regimen to counter this drug-drug interaction.

    The results were presented to the WHO guidelines review committee and have strengthened the WHO recommendation to use super-boosting in HIV/TB co-infected children when they are on an LPV/r-based therapy. This study has been completed and final results were presented in 2017 and published in 2018, showing that super-boosting is safe and effective.

 

 

Photo credit: Paul Kamau-DNDi