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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

The Centre de Recherches Médicales de Lambaréné (CERMEL) is a well-respected research institute in Gabon, with a strong track record of participation in clinical trials. It has, for example, contributed to trials of the RTS,S/AS01 malaria vaccine and a phase I Ebola vaccine trial.

However, CERMEL has lacked the capacity to carry out certain laboratory assays, which therefore have had to be outsourced to international partners. Developing the infrastructure and skills base to conduct these assays would extend the range of studies to which the centre could contribute and enable more timely monitoring of study participants.

The SECC project has strengthened the capacity of CERMEL to carry out Ebola-related research. Its biosafety manual has been revised and now includes standards to maintain safety in level 2 and 3 laboratories and for shipping of samples to biosafety level 4 facilities. A biological waste management plan consistent with international standards has been set up and a new biosafety committee established.

Through the SECC project, CERMEL has also introduced laboratory assays for monitoring replication of a virus-based Ebola vaccine, and trained staff in their use. This will allow on-site monitoring of replication of the vaccine virus in trials in children, enhancing safety monitoring.

Other training packages have been used to develop local skills in a range of molecular assays and management of laboratory facilities, including infectious disease surveillance, viral testing and exploratory testing of samples from patients with unidentified infections. This enhanced capacity will enable the centre to contribute to a wider range of research studies.

The project also supported the organisation of a four-day African Congress for Clinical Trials, which has the potential to become a regular scientific conference for all those involved in clinical trials in Africa.

A final aim of the project was to develop a decision-making framework to expedite responses to an Ebola outbreak. Following revision of the national Ebola preparedness and response plan, an evidence review board has been set up as a self-sustainable not-for-profit organisation to review scientific evidence of new strategies and interventions for Ebola and to recommend actions in case of an Ebola outbreak.

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 SECC project has strengthened the capacity of CERMEL, Gabon’s leading health research institute, to carry out research on Ebola and other viruses of epidemic potential. In addition, the principal applicant went on to secure a follow-on EDCTP fellowship. The project has also created a structure to promote evidence-based responses to new Ebola outbreaks.

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