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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

Although E. coli is found in all human guts, some strains – known as enterotoxigenic E. coli (ETEC) – cause a severe and potentially life-threatening diarrhoea. Around 75 million infections occur each year globally, causing at least 50,000 deaths, mainly in young children. Death rates are highest in Africa.

In addition, ETEC interferes with child growth and development, so it also has longer-term impacts on health and economic wellbeing

The ETVAX^® vaccine is the most advanced oral vaccine against ETEC. It is a mix of engineered strains of E. coli that produce high levels of four proteins known to stimulate protective immune responses, plus a hybrid protein that combines E. coli and cholera toxins. An adjuvant known as dmLT is also used, to stimulate more powerful immune responses.

Following positive results in European adults, the ETEC Vaccine Efficacy study will first conduct a series of safety studies in adults and progressively younger children in Zambia, including children 10–23 months old and infants 6–9 months old.

Assuming no safety issues arise, the project will then progress to a phase IIb study in infants 6–18 months old in The Gambia. The project will also provide a platform for testing of new point-of-care diagnostic tests for ETEC, which would provide a clearer picture of its disease burden.

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 study will provide key data on the efficacy of ETVAX^® in African children, and will also strengthen clinical trial and laboratory capabilities in Zambia and The Gambia, which will facilitate further vaccine trials.

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