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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

Infection with the single-celled parasite Trypanosoma brucei, human African trypanosomiasis, can be deadly without effective treatment. Enormous gains have been made in control of human African trypanosomiasis in recent decades, and the disease has been targeted for elimination as a public health threat by 2020. 

Nearly all cases of human African trypanosomiasis are caused by T. brucei gambiense, one of two human-infecting subspecies of T. brucei. Treatment of severe cases has until recently relied on intravenous drug infusions, requiring specialist care facilities. However, the Drugs for Neglected Diseases Initiative and its partners have developed a highly effective new treatment, fexinidazole, that can be given orally. Fexinidazole was given a positive scientific opinion by the European Medicines Authority in 2018 and gained marketing authorisation in the Democratic Republic of the Congo (DRC), the worst affected country, in the same year. 

Now recommended by WHO, fexinidazole represents a significant shift in clinical practice. Although much easier to administer, new procedures need to be introduced to ensure it is used effectively. For example, it needs to be administered with a meal to ensure adequate uptake. The FEX-g-HAT project aims to accelerate the introduction of fexinidazole by ensuring health systems and health workers in affected countries are able to make the treatment widely available to those who could benefit from it.

The main focus of the project will be on capacity building at national and local levels, drawing on recently updated WHO guidelines. Health workers are being trained and systems are being strengthened for monitoring of potential adverse reactions to the new treatment. As well as the DRC, the project is working with other African countries with a heavy burden of human African trypanosomiasis, such as Angola, Central African Republic, Guinea and South Sudan. The project will draw upon an existing network, the HAT Platform, which is supporting clinical training across more than 120 institutions in the region and promoting access to treatment. Longer-term follow-up will be taken on by WHO.

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.

Fexinidazole represents a major step forward for treatment of human African trypanosomiasis, particularly severe disease, reducing the need for challenging procedures such as lumbar puncture and intravenous injection. The FEX-g-HAT project will reduce delays in the implementation of this new treatment and ensure that people in sub-Saharan Africa benefit from fexinidazole as rapidly as possible.

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