“
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 in children under the age of five years. Current approaches to hospital care are still associated with relatively high mortality (9–16%). In addition, children are still at risk of dying after they are discharged from hospital, particularly if they are malnourished.

There is considerable scope to improve the treatment of young children with pneumonia. Key questions include when oxygen therapy should be used, and the most effective way it could be delivered, particularly in settings that lack equipment for mechanical ventilation. In addition, there is no formal evidence that supplementary feeding improves survival in under-nourished children. 

The COAST-Nutrition team is undertaking a clinical trial, funded by Wellcome and the UK Medical Research Council, which is evaluating different ways to deliver oxygen therapy to children hospitalised with pneumonia. EDCTP funding is being used to take advantage of this platform to assess the benefits of wider use of supplemental feeding, which is currently only given to the most severely under-nourished children.

Children that survive to 48 hours will be enrolled in a further trial to see if supplemental feeding to day 28 improves survival at 90 days. The team will also carry out other studies to see if simple measures or diagnostics are predictive of viral or bacterial pneumonia, to provide tools for improved care of children and targeting of antibiotic therapy in hospitals without microbiology services.

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 COAST-Nutrition trial will reveal whether extending the use of food supplementation beyond the most severely under-nourished children improves longer-term survival after hospitalisation for pneumonia. ‘Ready-to-use therapeutic foods’ are safe and widely available, so could be relatively straightforward to implement if evidence suggests that they reduce mortality.

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