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’s current Paediatric HIV portfolio includes:
One project in the translation phase:
- Two 4-in-1 LPV/r/ABC/3TC: The objective is to combine the four drugs needed for the treatment of paediatric HIV into a single unit, or fixed-dose combination, which is heat-stable, taste-masked, solid, does not contain alcohol or inappropriate solvents, and most importantly, is easy to dose. Following preliminary studies, the best formulation candidates in terms of bioavailability and taste-masking have been chosen for testing in healthy human volunteers in Phase I studies that are ongoing.
One project in the development phase:
LPV/r pellets + dual NRTI: Cipla has developed LPV/r pellets in capsules which can be opened and administered orally to small children, allowing the drug to be sprinkled on food and offering the advantage, over the current liquid formulation of these drugs, of being alcohol-free. The pellets do not require a cold chain and are less costly to transport; however, they have to be given with two other antiretrovirals which come in dispersible tablet form.
The DNDi project includes large-scale implementation studies (known as the LIVING study) to provide supportive clinical data on the acceptability, feasibility, efficacy, safety, and pharmacokinetics of LPV-based therapies in routine treatment settings and to provide early access to better formulations and facilitate registration in the countries concerned. Recruitment of patients is currently ongoing in Kenya (209 patients out of 350), Uganda (156 patients out of 350). Other countries where clinical sites will be initiated include Tanzania, South Africa and Zambia.
One project in the implementation phase:
Superbooster therapy paediatric HIV/TB: The drug rifampicin is the backbone of the regimen to treat TB in children. However, rifampicin reduces the “bioavailability” and hence the effectiveness of protease inhibitors such as LPV/r. This negative drug-drug interaction is a major challenge in treating kids infected with both HIV and TB. As part of its development of PI-based ARV regimens, DNDi carried out a pharmacokinetic (PK) study in 96 infants and young children co-infected with both 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.
Final results show that LPV drug levels during HIV/TB co-treatment using the superboosting approach is as good as when children return to standard LPV/r-based antiretroviral therapy. Superboosting was safe and well tolerated. Results were shared with WHO to support a change in guidelines for the management of HIV/TB co-infections in children, which was done in 2016.
In 2017, a follow-on study currently awaiting ethical approval will examine the safety and efficacy of super-boosting with ritonavir powder and other solid antiretovirals including LPV/r pellets and dual NRTI dispersible tablets.
Photo credit: Scholars & Gentlemen-DNDi