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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

Tuberculosis (TB) treatment outcome is not only impaired by co-morbidities such as HIV infection, but also by insufficient consideration of the relationship between the dosing of the administered TB drugs, the concentrations achieved, and eventually, the desirable and undesirable responses. Especially dosing of TB drugs for children is not well substantiated and the concept of using higher doses of rifampicin has not been translated to the treatment of children.

Dr Semvua proposed to conduct a phase IIa dose-finding clinical study to find the rifampicin dose in children that yields plasma concentrations similar to those achieved in adults after a 35 mg/kg daily dose. This will answer an important scientific question of direct public benefit.

As regards capacity development, the fellow will receive hands-on training from a mentor of the Radboudumc, an academic research hospital in the Netherlands, during all parts of the study. Skills to perform bio-analysis of TB drugs will be obtained through the pharmacokinetic laboratory at Radboudumc. The fellow will also attend courses on bioanalytical method validation and pharmacokinetic data analysis as well as relevant conferences. All this will enable the development and validation of bioanalytical methods for TB drugs at the Biotechnology Laboratory in the Kilimanjaro region. The fellow will mentor two next-generation scientists on the principles of bio-analysis of drugs and pharmacokinetic data analysis through PhD and Master training at the Kilimanjaro Christian Medical University College.

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 team of experts developed through this proposal will continue to design and conduct pharmacokinetic studies focused on infectious disease threats in Tanzania and contribute to the global effort to fight poverty-related infectious diseases.

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