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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

TB remains the leading infectious cause of death. More than a quarter of all TB deaths occur in sub-Saharan Africa; 417,000 people died in 2016, while 2.5 million fell ill with TB.

The high burden of TB in the region is due in part to low rates of detection and delayed diagnosis, providing opportunities for the disease to spread. Unfortunately, TB is difficult to diagnose, and it is becoming clear that clinical signs such as long-term cough and even commonly used microscopy ‘smear’ tests are not a reliable guide to infection. Much more aggressive approaches to case detection are therefore required.

The EXIT-TB project, connecting institutions in Ethiopia, Kenya, Sudan, Tanzania and Uganda, aims to promote the introduction into routine practice of a range of measures that have been shown in research settings to improve the detection of TB cases. It will serve as an exemplar of projects accelerating the translation of research into policy and practice.

Four specific approaches are being promoted. One is intensified TB case finding through screening of all patients reporting to outpatient departments with a cough of any duration. TB case finding is also being integrated into reproductive and child health clinics and diabetes clinics.

Further cases are being identified through screening of all patients living with HIV who attend care and treatment centres, irrespective of their symptoms. The final strand is targeted contact tracing for all TB patients with child household members, who are at significant risk of infection.

The project is spearheading and evaluating the implementation of this package of interventions at multiple centres in four sub-Saharan African countries, including both rural and urban facilities. It will explore the feasibility of implementation and identify barriers to implementation and challenges that health systems face in delivering the EXIT-TB package in the different settings; it will also undertake a cost-effectiveness analysis.

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 EXIT-TB project will provide essential data on the impact of the package of interventions on TB case detection, as well as on the practical challenges associated with its introduction into routine practice. It will inform revision of guidelines in integrated care at HIV/AIDS, reproductive and child health clinics, and diabetes clinics, and provide evidence to support wider introduction within participating and other sub-Saharan African countries.

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