A key component of the UN Global Plan for the elimination of paediatric HIV is the scale up of early diagnosis of HIV for all exposed infants and universal treatment of HIV-infected children. Improving access to early HIV diagnosis of infants will lead to an increase in demand for ART in young children up to 2020 despite the absolute decline in new infections due to increased uptake of more effective strategies for the prevention of mother to child transmission of HIV^[i]

In the absence of ART, up to 35 % of HIV-positive children in sub-Saharan Africa will die in their first year of life, and 80% will die from AIDS-related causes before their fifth birthday^[ii].

However, few drugs are approved for infants and toddlers and combination antiretroviral therapies (cARTs) which must associate 3 or 4 drugs that act synergistically to suppress HIV replication are limited and complex to administer. Existing paediatric cARTs which typically combine the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine-(NVP) with two nucleoside reverse transcriptase inhibitor (NRTIs), lamivudine (3TC) plus either abacavir (ABC) or zidovudine (ZDV) or stavudine (d4T), are not optimal for newly infected infants because they have viral loads 10 to 100 times higher than older children and are often infected with viruses already resistant to NVP, a commonly used antiretroviral for PMTCT[iii].

For infants, the only alternative to NVP is the protease inhibitor (PI) lopinavir (LPV) which needs to be boosted with ritonavir (RTV) in a 4:1 ratio (LPV/r) to reach therapeutic blood levels[iv]. However, due to their chemical properties, these two drugs are formulated with a high alcohol content (42% for LPV/r) and solvent (15% propylene glycol for LPV/r), taste very bitter, are difficult to administer, are unstable in tropical climates (LPV/r requires refrigeration prior to dispensing), and are expensive. While accumulating evidence demonstrates the superior clinical efficacy of LPV/r over NVP regardless of the child’s prior exposure to antiretrovirals for PMTCT, widespread LPV/r use is largely limited to South Africa where the health infrastructure is able to overcome the logistical obstacles to its use. Elsewhere in Africa, children receive NVP-based fixed-dose combinations (FDCs) that are easier to use, inexpensive, but of significantly lower efficacy.

WHO treatment guidelines have been revised in 2013 and reemphasize the need to treat all HIV-infected children below 5 years of age and, for children less than 3 years of age to initiate therapy with a PI-based regimen regardless of prior exposure to antiretrovirals for PMTCT[v]. However, by making this recommendation “when feasible,” WHO recognizes the programmatic complexity of providing infants and young children with the liquid formulations described above.

Cipla pharmaceuticals, India, have also developed LPV/r adult (200mg/50mg) and paediatric tablets (100mg/25mg) using melt extrusion technology, as well as pellets (mini-‘melt’ tablets formulation (in the same 4:1 drug ratio), stored in 40/10 mg capsules, which can be opened and administered orally to small children, as it allows the drug to be easily mixed with food and offers the other advantage of being alcohol-free.

LPV/r pellets represent a clear advantage in comparison with the liquid formulation in terms of logistic, acceptability but the poor taste is still present[vi].

DNDi created a paediatric HIV program in 2011 with objectives to formulate two heatstable LPV/r FDCs and a heatstable RTV solid formulation which are well taste masked. Before these formulations are made available, DNDi is committed to make alternative formulations such as the LPV/r pellets developed by Cipla in combination with existing dual NRTI FDCs available for treatment for children infected with HIV in resource poor settings.

The implementation study described below will be carried out to provide supportive clinical data on the feasibility, efficacy, safety, and PK of LPV based therapies in routine treatment setting and will be based on the existing LPV/r pellets which already represent a clear advantage in comparison with the liquid formulation.