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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Pneumonia is the leading cause of death of children under five years of age. Globally, it kills an estimated 1.4 million children every year, and accounts for 18% of deaths of young children. An estimated 500,000–750,000 of these deaths occur in sub-Saharan Africa.

WHO recommends that hospitalised children with severe or very severe pneumonia should be given injectable antibiotics for at least five days. However, this leads to long hospital stays, high costs and an increased risk of hospital-acquired infection.

The PediCAP study is investigating less intensive treatment strategies based on a switch from injected to oral antibiotics, for which little evidence currently exists. Treatment could be switched to amoxicillin, or to a co-amoxiclav, a combination of amoxicillin and a second type of antibiotic; the latter would protect against a wider range of bacteria but could have more side effects and might select for antibiotic resistance. It is also unclear how long oral antibiotics should be given for – courses should be long enough to kill pathogens but not so long that they promote the development of resistance.

The PediCAP team will use an innovative trial design to compare the switch from injected antibiotics to either amoxicillin or to co-amoxiclav, and to assess different durations of treatment. As well as recovery rates, the trial will monitor side effects and the development of resistance. It will also examine whether optimal duration of treatment depends on factors such as age or severity of disease, which could allow treatment regimes to be tailored to particular subsets of patients.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The PediCAP study will fill a large gap in the evidence base for treatment of pneumonia in children. As increasing numbers of children are being treated for pneumonia in hospital, optimised treatments that achieve high cures rates while minimising lengths of hospital stay, side effects and resistance could have a major impact.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact