“
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 infants are thought to be protected against malaria during the first months of life mainly due to maternal antibodies, malaria in early childhood is not uncommon in high-transmission settings. Susceptibility to the infections varies between individuals and, therefore, putting into question the protective effect of maternal antibodies. In such a context, factors that modulate malaria risk/protection in early childhood are not fully understood. Further field studies focusing on the role of maternal antibodies are needed.

A three-month placement at the host institution, the Barcelona Institute for Global Health (ISGlobal), will provide Dr Hamtandi Natama with the necessary training in qSAT multiplex antibody detection using Luminex^® platform, immune cell isolation, stimulation, phenotyping and quantification using flow cytometry, data quality control and analysis). ISGlobal also offers the facilities to analyse a set of cord blood samples (n=715) for maternal antibody detection.

The objectives of the project are to 1) generate data on maternal antibodies (IgG/subclasses) relevant for malaria protection during the first months of life, which will guide future studies on malaria immunology in early childhood; 2) acquire skills and competence in immunological techniques and methods, and; 3) develop a compelling proposal for funding after the fellowship.

The placement will be followed by a three-month reintegration period at the home institution. This will be used to train peers on a set of immunological techniques. Moreover, the fellow will complete the statistical analysis, data interpretation and preparation of a publication on the maternal antibodies research and continue the development of Dr Natama’s follow-on project based on the research outputs from the placement.

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 preparatory fellowship will have an impact at several levels. First, it will contribute knowledge of the role of maternal antibodies in malaria protection in infants living in malaria-endemic settings, promote high-quality malaria immunology research and build capacity through the training of colleagues. Secondly, it will prepare the home institution (laboratory development) for future immunological malaria studies and strengthen the relationship with ISGlobal. Thirdly, the fellow will consolidate his skills and competence in malaria immunology research, his competitiveness in attracting grants and establish himself as an independent malaria researcher in his home institution.

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