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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

An estimated 2.5 million people fall ill with TB in sub-Saharan Africa every year, with more than 400,000 deaths. These figures include 1 million new infections in children and 250,000 deaths.

The challenges of TB are being exacerbated by the emergence of multidrug-resistant TB and extensively drug-resistant TB, which require long periods of hospitalisation and treatment.

Professor Keertan Dheda is one of Africa’s leading authorities on TB. He is Head of the Division of Pulmonology at the University of Cape Town, having built up a large research group from scratch. His group’s work has a strong focus on developing improved services for local populations in the Western Cape, and in South Africa and Africa more generally. He has pioneered the adoption of new techniques into clinical practice, and developed research programmes in all areas of TB diagnosis, treatment and care. He has led several successful EDCTP-funded projects on TB diagnostics, and was awarded the 2018 EDCTP Scientific Leadership Prize.

In his EDCTP Senior Fellowship, Professor Dheda aims to further develop his own leadership capabilities, and build local capacity in new genomics and other ‘omics’ technologies. This will include setting up a genome sequencing platform to support the training of early-career researchers in a technology increasingly central to infectious disease research. 

His fellowship will build on a trial being funded by the South African Medical Research Council, NExT RCT, led by Professor Dheda, which is evaluating a new six-month needle-free regimen for multidrug-resistant TB. Biobanked samples will be used in a range of projects. One study is evaluating biomarkers potentially associated with response to TB treatment – current trials are long and costly because no good markers currently exist that predict treatment responses. A second study will use next-generation genome sequencing to identify resistance mutations. A third study will investigate methods to enable genome sequence information to be derived directly from clinical 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.

Professor Dheda’s Senior Fellowship will enable him to undertake professional development activities so he can extend his leadership role in the African and global TB research community. In addition, it will support the introduction of new technologies that will accelerate research on diagnosis and treatment of this critical disease, and facilitate the training of junior researchers (a postdoctoral fellow and a PhD student).

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