R&D status September 2014: DNDi Paediatric HIV programme

[September 2014]

HIV is transmitted to children during pregnancy, delivery and through breastfeeding. An estimated 3.3 million children below the age of 15 were living with HIV in 2012, more than 90% of whom were in Sub-Saharan Africa.

Under the 2013 WHO guidelines, infants, under the age of three, should be treated with an antiretroviral treatment (ART) combination that includes protease inhibitors (PI). The combination of a boosted PI with two nucleoside reverse transcriptase inhibitors (NRTIs) is considered by many experts as the most effective first-line therapy for infants and children. However, this combination therapy is not being widely used. The only available PI for young children, lopinavir/ritonavir (LPV/r) is not adapted to children considering that the oral solution formulation is unpalatable, contains alcohol and is logistically difficult to manage.

HIV-infected infants co-infected with tuberculosis (TB) face additional difficulties with their treatments as TB therapies interact with the HIV drugs reducing their levels in blood and so reducing their effectiveness. A stand-alone ritonavir booster formulation is being developed that can be added to any PI-based paediatric ARV regimen, in order to counteract the negative drug interactions between PIs and rifampicin-containing TB treatment.

To address WHO recommendations and HIV-infected infants’ specific needs, DNDi has set up a paediatric HIV programme that is currently running:

Translation
Translation


Two projects in the translation phase
:

  • Pre-clinical testing of two ‘4-in-1’ LPV/r based FDC granules. The development plan in partnership with Cipla and support of UNITAID, includes putting together all four drugs needed for the treatment of HIV in children into a single unit, also known as a fixed-dose combination (FDC), which is heat-stable, well taste-masked, solid, does not contain alcohol or inappropriate solvents and, most importantly, is easy to dose. The two FDCs in development are lopinavir/ritonavir/zidovudine/lamivudine (LPV/r/AZT/3TC) and lopinavir/ritonavir/abacavir/lamivudine (LPV/r/ABC/3TC)
  • A pharmacokinetic study to assess the safety and acceptability of superboosted LPV/r in liquid for TB/HIV patients started in 2013 in South Africa. The study also evaluates the pharmacological efficacy of adding the booster and assesses the virological outcome of the procedure. It has so far recruited 67patients out of 90 at five sites.

Development
Development

 

One project in the development phase:

  • An implementation study will start in Africa this year, using a PI-based treatment with existing LPV/r-based solid formulations (before the availability of the ‘4-in-1’ FDC) called ‘pellets’ that will be used in combination with NRTI dispersible tablets.

DNDi is also partnering with UNITAID, CHAI and the Medicines Patent Pool to bring together key stakeholders in the Paediatric HIV Treatment Initiative (PHTI) to reduce barriers to the development and delivery of WHO recommended antiretroviral formulations for children.

By 2015-2016, DNDi aims to deliver from its paediatric HIV portfolio:

  • Two new all-in-one paediatric formulations containing a PI (LPV/r) and two NRTIs (ABC or AZT or 3TC
  • One stand-alone paediatric booster RTV for HIV-TB co-infected children


For more information on the partners and donors involved in DNDi paediatric HIV programme, please click on each hyperlink that will refer you to each project.