WHAT IS DNDi DOING TO ADDRESS UNMET TREATMENT NEEDS?
In 2010, DNDi was called on by various organizations, including Médecins Sans Frontières, WHO, and UNITAID, to apply its expertise to the development of paediatric HIV treatments. DNDi’s position, notably that paediatric HIV is a neglected disease, was published as a ‘Perspective’ in the New England Journal of Medicine in August 2011.
DNDi is pursuing two objectives to address the needs of HIV-infected children:
- Develop and register two solid first-line 4-in-1 LPV/r-based fixed-dose combinations (FDCs) with two NRTIs. All components of the combination will be developed in the form of tastemasked granules, which are stable with no need for refrigeration, presented in a single unit with appropriate strengths to accommodate weight band dosing.
- Evaluate the superboosting strategy: i.e. increasing the LPV:RTV ratio that can effectively and safely counteract the negative drug-drug interactions between PIs and rifampicin-containing TB treatments.
As a short-term strategy, DNDi will start testing the use of PI-based treatment with Cipla’s LPV/r-based pellets before the ‘4-in-1’ FDC becomes available, in order to provide better treatment for infants today and promote in-country adoption. DNDi participated in the CHAPAS-2 trial that compared LPV/r pellets to the LPV/r liquid formulation. These pellets are being used in combination with NRTI dispersible tablets in implementation studies (LIVING study), which started in 2015. In the longer-term, DNDi is working with Cipla, its industrial partner, on combining taste-masked LPV/r granules or pellets with two NRTIs into a single unit dose. This modular concept is flexible, so that any of the components can eventually be substituted to provide new fixed-dose combinations. In order to address the needs of HIV/TB co-infected children, DNDi aims to assess the addition of ritonavir for superboosting LPV/r at a 1:1 LPV:RTV ratio. DNDi is conducting a study to establish the pharmacokinetics, efficacy, and safety of superboosted LPV/r in children in South Africa with the existing ritonavir solution. Interim results look promising for this approach and the study is being extended to include all solid formulations.
The ideal first-line treatment for paediatric HIV would be a protease inhibitor-based all-in-one antiretroviral regimen for HIV-infected children which is safe and efficacious, is an adapted formulation suitable for infants and children, is an easy-to-use fixed-dose combination, is palatable, addresses drug-drug interaction with medicines for tuberculosis, and is adapted to tropical climates (no refrigeration needed).
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/ AZT.
- Immediate introduction of the recently US FDA approved LPV/r-pellets, before the availability of better-adapted 4-in-1 products.