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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 much progress has been made in the battle against malaria, it still kills more than 400,000 people in sub-Saharan Africa every year, most of them children.

One of the most successful strategies for malaria prevention has been seasonal malaria chemoprevention, in which antimalarial drugs – usually sulfadoxine–pyramethamine (SP) and amodiaquine – are given to healthy young children to prevent malaria at times of year when they are at greatest risk, generally during the rainy season.

However, there are concerns that SP-based chemoprevention is becoming less effective due to the spread of drug resistance. In addition, the success of malaria prevention in young children means that they are not acquiring natural immunity to infection, leading to increasing numbers of infections in older, school-age children. Such children may also act as a reservoir facilitating the spread of malaria during times of low transmission.

Dr Traoré’s project will provide important data on the ability of DHA–PQ to prevent malaria in school-age children and reduce community transmission of malaria. This evidence will inform decision-making on use of seasonal malaria chemoprevention in older children and the most appropriate drug combination to use. As well as supporting Dr Traoré’s development as a senior researcher, the project is also helping to build capacity through the training of master’s and PhD students.

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.

Dr Kusi’s work will fill a key evidence gap, shedding light on the impact of HBV and malaria parasite co-infections on immune responses. The findings will have important implications for the treatment of people with HBV who contract malaria. In addition, as malaria vaccines move closer to routine use, the results will help to determine how effective a vaccine is likely to be in populations with high levels of HBV infection.

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