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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

Molecular tests that identify SARS-CoV-2 genetic material are the gold standard method of diagnosis, but require special facilities rare in sub-Saharan Africa. Tests that detect viral proteins (antigen tests) offer the potential for point-of-care detection of infection.

A complementary role is played by antibody tests. As antibodies to SARS-CoV-2 take 2–3 weeks to appear, they are not suitable for identifying new infections but can be used to track infection in populations so that the spread of COVID-19 can be better understood.

The COVADIS project is evaluating a range of tools, including antigen and antibody tests, to provide a detailed picture of the evolution of immune response in individuals and the spread of infection in communities.

A cohort of 100 confirmed COVID-19 patients is being recruited in Burkina Faso and The Gambia. They and their household contacts will be followed for six months, weekly for the first month and then at 3 months and 6 months. The project will assess viral load, monitor for production of antibodies, and determine how many asymptomatic infections occur in households.

Specifically, the project will evaluate a point-of-care antigen-detection test developed by one of the European partners. This test, evaluated on stored samples from Belgium, has very high specificity (99%), although lower sensitivity (60%); sensitivity may be higher when fresh samples are used. Because of the high specificity, a positive result could be considered a true positive, obviating the need for confirmatory molecular testing.

The project will also establish a platform that will enable antibody responses to be assessed using convenient dried finger-prick blood samples.

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 COVADIS project will generate data on use of a rapid and practical point-of-care antigen-detection test for COVID-19 in a sub-Saharan African setting. As test results would be available within 15 minutes, isolation and contact tracing could begin almost immediately. The study will also generate important evidence on the acceptability and usability of the test, including potential use in health facilities and in people’s homes.

Work on the patient cohort will provide important data on the dynamics of transmission in households, including the role of asymptomatic infections. The intensive characterisation will enable links to be drawn between viral shedding, immune responses and clinical symptoms. The data will be highly relevant to public health responses, and the project team has established close links with ministries of health in the two countries to ensure rapid communication of results to local health authorities.

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