DNDi aims to deliver:
- Two solid taste-masked first-line LPV/r-based fixed-dose formulations in combination with two NRTIs, 3TC plus either ABC or AZT.
- Immediate introduction of the recently US FDA approved LPV/r-pellets, before the availability of better-adapted 4-in-1 products.
DNDi has made significant progress towards its goal of developing optimal child-adapted antiretroviral (ARV) formulations:
One project in the translation phase:
- Two 4-in-1 LPV/r/ABC/3TC: A first-line “4-in-1” fixed-dose combination (abacavir/lamivudine/lopinavir/ritonavir) is on track to be submitted for registration in late 2018. The combination of protease inhibitors such as lopinavir/ritonavir (LPV/r) with two nucleoside reverse transcriptase inhibitors (abacavir and lamivudine) is considered by the World Health Organization (WHO) as the most effective first-line therapy for infants and children under three years of age. The 4-in-1 will be taste-masked and heat-stable – a great improvement over the current high-alcohol content LPV/r syrup.In 2017, pharmacokinetic studies in healthy human volunteers were conducted with a final 4-in-1 formulation. Paediatric studies are planned in Uganda and South Africa where the levels of 4-in-1 in children across a large weight range will be measured and compared to the standard treatment. Safety, feasibility, and efficacy data on this new formulation will also be generated to provide evidence for worldwide scale-up.
One project in the development phase:
LPV/r pellets + dual NRTI: In September 2015, DNDi launched the LIVING study with five sites in Kenya to provide early access to LPV/r “oral pellets,” which are taken orally. The study has been expanded to Uganda and Tanzania, and as of November 2017 has enrolled 750 patients. The study is intended to demonstrate the effectiveness, safety, and acceptability of LPV/r oral pellets in the field and pave the way for the 4-in-1.Results were presented at the end of 2017, showing oral pellets are effective, well tolerated and well accepted by caregivers and children. DNDi will support LIVING study sites and other programmes, as well as national governments, to transition from the interim LPV/r oral pellet to the 4-in-1 when it is available.
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 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.The results were presented to the WHO guidelines review committee and have strengthened the WHO recommendation to use super-boosting in TB/HIV co-infected children when they are on a LPV/r-based therapy. This study has been completed and final results were presented in 2017, showing that super-boosting is safe and effective.
Photo credit: Scholars & Gentlemen-DNDi