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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

Control of the 2014–16 West African Ebola epidemic was held back by the lack of licensed treatments. Similarly, no licensed treatments are available for other viral haemorrhagic fevers with high fatality rates.

However, although the burden of such infections is highest in sub-Saharan Africa, relatively few centres have the specialist facilities and expertise to undertake early-phase clinical research on new therapeutics.

The Infectious Diseases Institute at Makerere University College of Health Sciences in Uganda is a well-established centre of excellence in infectious disease research. The Capa-CT project has built on this foundation, enhancing its capacity to undertake early-phase clinical studies.

To support skills development, the project organised four training workshops on key aspects of clinical management, pharmacokinetic modelling and statistical methods for drug development, delivered to more than 100 local staff. Training was supported by a professor-in-residence initiative. Individual staff received postgraduate training in pharmaceutical medicine and regulatory affairs. One staff member also secured a one-year clinical trial unit placement through a separate EDCTP career development award.

The project also supported upgrading of research facilities and the Institute’s research pharmacies. The Institute also identified potential intensive care unit referral sites and suitable patient transfer arrangements. In addition, the project introduced a range of new approaches to build quality management capacities, and catalysed the creation of a new position, a clinical trials quality manager.

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 Capa-CT project has established capacity for phase I clinical trials at a leading site for infectious disease research in Uganda. The skills development also enabled the Institute to join a major international consortium for phase II drug development studies on new interventions for Ebola and Marburg virus infections in an outbreak setting. In addition, the Institute was able to secure further funding for the Capa-CT II project through a later EDCTP Ebola-specific call for proposals.

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